RESUMO
BACKGROUND: We sought to determine the prevalence of MS on the Isle of Man in 2006 and 2011, and the incidence and mortality rates over this interval. METHODS: Cases were identified by hospital medical record review, General Practitioners and the local MS Society. The significance of the change in prevalence over time and the significance of differences in frequencies by sex and place of birth were assessed by Poisson regression. RESULTS: The 2006 prevalence was 153.64 per 100,000 persons and the 2011 prevalence was 179.89. The prevalence was higher among females and persons born in the Isle of Man at both time points. The 2006-2011 incidence rate was 6.86 per 100,000 person-years, much higher among females and persons born in the Isle of Man. The prevalence sex ratios in 2006 and 2011, 2.77 and 2.59, respectively, and the incidence sex ratio, 2.19, are similar to others found in the region. The mortality rate over the study period was 2.84 per 100,000 person-years, this solely among persons born overseas. CONCLUSIONS: This is the first study of MS epidemiology in the Isle of Man, finding this area to be of high prevalence and to have one of the highest incidence rates in the UK region.
Assuntos
Esclerose Múltipla/epidemiologia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Incidência , Longevidade , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/mortalidade , Esclerose Múltipla/terapia , Distribuição de Poisson , Prevalência , Prognóstico , Fatores Sexuais , Reino Unido/epidemiologia , Reino Unido/etnologiaRESUMO
BACKGROUND AND PURPOSE: Neuromyelitis optica (NMO) or Devic's disease is a rare inflammatory and demyelinating autoimmune disorder of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), which is distinct from multiple sclerosis (MS). The guidelines are designed to provide guidance for best clinical practice based on the current state of clinical and scientific knowledge. SEARCH STRATEGY: Evidence for this guideline was collected by searches for original articles, case reports and meta-analyses in the MEDLINE and Cochrane databases. In addition, clinical practice guidelines of professional neurological and rheumatological organizations were studied. RESULTS: Different diagnostic criteria for NMO diagnosis [Wingerchuk et al. Revised NMO criteria, 2006 and Miller et al. National Multiple Sclerosis Society (NMSS) task force criteria, 2008] and features potentially indicative of NMO facilitate the diagnosis. In addition, guidance for the work-up and diagnosis of spatially limited NMO spectrum disorders is provided by the task force. Due to lack of studies fulfilling requirement for the highest levels of evidence, the task force suggests concepts for treatment of acute exacerbations and attack prevention based on expert opinion. CONCLUSIONS: Studies on diagnosis and management of NMO fulfilling requirements for the highest levels of evidence (class I-III rating) are limited, and diagnostic and therapeutic concepts based on expert opinion and consensus of the task force members were assembled for this guideline.
Assuntos
Neuromielite Óptica/diagnóstico , Neuromielite Óptica/terapia , Eletrodiagnóstico , Humanos , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Troca PlasmáticaRESUMO
INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
Assuntos
Autoanticorpos , Imunoglobulinas Intravenosas , Adulto , Criança , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Glicoproteína Mielina-Oligodendrócito , Plasmaferese , Inquéritos e QuestionáriosRESUMO
For most patients presenting with a spinal cord syndrome MR scanning has become the key investigation in establishing the diagnosis. However, myelopathy with normal spinal imaging remains a common clinical conundrum. In this review we discuss the diagnoses to consider for the neurologist presented with a patient with "MR normal myelopathy". We will illustrate this scenario with a series of short cases and consider the further investigation of "MRI normal" myelopathy.
Assuntos
Encéfalo/patologia , Imageamento por Ressonância Magnética , Doenças da Medula Espinal/diagnóstico , Medula Espinal/patologia , Adolescente , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In clinical trials drop out bias reduces the validity of results. This is a particular problem in long-term multiple sclerosis (MS) studies, particularly when patients become progressively disabled and have increasing difficulty attending assessment clinics. OBJECTIVE: To assess the validity of nurse led telephone assessment of Expanded Disability Status Scale (TEDSS) in MS patients with EDSS scores >6.0. METHODS: We performed a multi-centre, single blind trial to assess nurse derived TEDSS against physician face-to-face EDSS scores derived from neurological examination (FEDSS) in patients with clinically definite MS and EDSS >6.0. RESULTS: Ninety patients (n=15 primary progressive MS, n=74 secondary progressive MS, n=1 relapsing remitting MS) had a mean baseline FEDSS of 7.5. TEDSS correlated with FEDSS (r=0.76, p<0.0001) and kappa scores for perfect agreement, within 0.5 of an EDSS points, and within 1 EDSS point were 0.25, 0.86, and 1.0 respectively. Intra-class correlation between the scoring systems was 0.88, representing a high level of agreement. CONCLUSION: Nurse-led telephone assessment of EDSS gives good agreement with physician derived face-to-face EDSS in MS patients with higher disability scores. This may be a valuable tool to improve clinical follow-up in routine clinical practice and improve patient retention in long-term outcome studies.
Assuntos
Avaliação da Deficiência , Pessoas com Deficiência , Entrevistas como Assunto/métodos , Esclerose Múltipla/diagnóstico , Enfermeiras e Enfermeiros , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Método Simples-CegoRESUMO
Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor samples, allelic deletions were sought with 15 probes identifying restriction fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20, and 22. Evidence of amplification or rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of Gs alpha were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of Gs alpha were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of Gs alpha are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype.
Assuntos
Adenoma/genética , Neoplasias Hipofisárias/genética , Adenoma/patologia , Alelos , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 7 , DNA de Neoplasias/genética , Éxons , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/genética , Rearranjo Gênico/genética , Genes Supressores/genética , Heterozigoto , Humanos , Imuno-Histoquímica , Mutação/genética , Oncogenes/genética , Neoplasias Hipofisárias/patologia , Reação em Cadeia da PolimeraseRESUMO
We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.
Assuntos
Carbamazepina/efeitos adversos , Hipersensibilidade a Drogas , Adulto , Dermatite Esfoliativa/induzido quimicamente , Eosinofilia/induzido quimicamente , Feminino , Humanos , Nefropatias/induzido quimicamente , Reação Leucemoide/induzido quimicamenteRESUMO
BACKGROUND: Oxidative stress has been implicated in inflammatory demyelination. The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTM1/GSTT1), encode low activity variants (GSTP1), or are associated with variable inducibility (GSTM3). OBJECTIVES: To investigate the association between clinical outcome in MS and allelic variants of GSTM1, GSTM3, GSTT1, and GSTP1. METHODS: Four hundred patients with clinically definite MS were studied. Disability was measured using the Kurtzke Expanded Disability Status Scale (EDSS). Disability was graded as mild (EDSS 0-4), moderate (4.5-5.5), or severe (EDSS 6-10). PCR-based genotyping was performed using DNA extracted from lymphocytes. Significant associations between GST genotypes and clinical outcome were corrected for gender, onset age, and disease duration using logistic regression. RESULTS: We found that the GSTM3 AA genotype was associated with severe disability in patients with a disease duration of more than 10 years (p = 0.027, n = 177, OR = 2.4, 95% CI = 1.1-5.0). Homozygosity for both GSTM1*0 and GSTP1*Ile105 containing allele was associated with severe disability in patients with a disease duration greater than 10 years (p = 0.022, n = 179, OR = 5.0, 95% CI = 1.3-19.8). CONCLUSIONS: Our results suggest that long-term prognosis in MS is influenced by a genetically determined ability to remove the toxic products of oxidative stress.
Assuntos
Avaliação da Deficiência , Glutationa Transferase/genética , Esclerose Múltipla/genética , Esclerose Múltipla/fisiopatologia , Polimorfismo Genético/genética , Adulto , Idade de Início , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Interleukin-10 (IL10) is an anti-inflammatory cytokine which may modulate disease expression in multiple sclerosis (MS). Three dimorphic polymorphisms within the IL10 promoter region at positions - 1082, -819 and -519 have previously been identified. The - 1082*A allele has been associated with low and the - 1082*G allele with high in vitro IL10 production. We have genotyped 185 Caucasian MS patients and 211 ethnically matched controls for each of these three dimorphisms. MS patients were stratified for severity of disease outcome. No associations were found for any IL10 promoter polymorphisms when the MS cases were compared with controls or with disease outcome with regards to disability. IL10 polymorphism does not appear to be associated with MS or to influence disease progression.
Assuntos
Interleucina-10/genética , Esclerose Múltipla/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologiaRESUMO
We studied the association between clinical outcome in MS and allelic variants single nucleotide polymorphisms (SNPs) of interleukin-1alpha (IL-1alpha), IL-1beta and a variable number tandem repeat (VNTR) in IL-1 receptor antagonist (IL-1RN). A total of 377 patients with MS were studied. Significant associations between IL-1 genotypes and clinical outcome were found using logistic regression after correction for gender, onset age and disease duration. The same trends were subsequently demonstrated in a second independent group of 67 primary progressive patients. Our results suggest that genetically determined immunomodulation mediated by IL-1 influences long-term prognosis in multiple sclerosis (MS).
Assuntos
Adjuvantes Imunológicos/genética , Predisposição Genética para Doença/genética , Interleucina-1/genética , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Polimorfismo Genético/genética , Sialoglicoproteínas/genética , Adulto , Idade de Início , Estudos de Casos e Controles , Progressão da Doença , Feminino , Frequência do Gene/genética , Genótipo , Homozigoto , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/imunologia , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Polimorfismo Genético/imunologia , Fatores Sexuais , Sialoglicoproteínas/imunologiaRESUMO
The association between susceptibility to multiple sclerosis (MS) and the class II MHC allele HLA-DRB1*15 is well established although a possible relationship between this allele and outcome in MS is less clear. HLA-DRB1 typing was performed on 375 unrelated white patients with clinically definite MS and on 367 healthy controls. Putative associations of the gene with outcome were examined by dividing patients into two groups: those with an EDSS of 0-5.5 (mild/moderate disease) and those with an EDSS of 6-10 (severe disease). In order to minimise the effects of disease variability patients with a disease duration of at least 10 years or 15 years were examined. As subsidiary HLA-DRB1*03 and HLA-DRB1*04 associations have been previously reported, the effect of these alleles was also examined. As expected, HLA-DRB1*15 was found more frequently in patients than in controls (P < 0.000001). HLA-DRB1*15 positive patients had a significantly earlier age at onset than HLA-DRB1*15 negative patients. No significant associations were noted between HLA-DRB1*15 and outcome in the total patient group or in patients with a disease duration of 10 years or longer. In patients with a disease duration of at least 15 years HLA-DRB1*15 negative status was associated with a worse prognosis, although this did not remain significant after correction for multiple testing. It is thus likely that the contribution of HLA in MS is primarily towards onset and initial triggering mechanisms rather than influencing disease progression, chronicity and severity.
Assuntos
Predisposição Genética para Doença , Antígenos HLA-DR/genética , Esclerose Múltipla/genética , Adulto , Idade de Início , Estudos de Casos e Controles , Doença Crônica , Progressão da Doença , Feminino , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Prognóstico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients. SEARCH STRATEGY: We searched the Cochrane MS Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (January 1966 to June 2003), EMBASE (January 1988 to June 2003), bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies. SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Twenty-six placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam, threonine and cannabinoids) and thirteen comparative studies met the selection criteria and were included in this review. Only fifteen of these studies used the Ashworth scale, of which only three of the eight placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.
Assuntos
Esclerose Múltipla/complicações , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Humanos , Espasticidade Muscular/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients. SEARCH STRATEGY: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies. SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.
Assuntos
Esclerose Múltipla/complicações , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Humanos , Espasticidade Muscular/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients. SEARCH STRATEGY: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies. SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.
Assuntos
Esclerose Múltipla/complicações , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Humanos , Espasticidade Muscular/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To define the rate, timing, and clinical risk factors for the development of autoimmune disease (AID) after alemtuzumab treatment for multiple sclerosis (MS). METHODS: We analyzed prospective clinical and serologic data from 248 patients with MS treated with alemtuzumab, with median follow-up of 34.3 months (range 6.7-107.3). RESULTS: Novel AID developed in 22.2%. Thyroid AID was most frequent (15.7%). A range of hematologic, renal, and dermatologic AID were also observed as was asymptomatic development of novel autoantibodies. AID was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. No new cases of AID were identified 60 months or more after initial treatment and risk of AID was independent of total alemtuzumab dose or interval of dosage. While established risk factors for AID including sex and age had no impact on AID frequency, both family history (odds ratio = 7.31, 95% confidence interval 3.02-17.68) of AID and a personal smoking history (odds ratio = 3.05, 95% confidence interval 1.50-6.19) were predictive of AID expression. CONCLUSIONS: Cumulative risk for AID in MS following alemtuzumab is 22.2%, most frequent between 12 and 18 months following first dose and evident for up to 5 years. Individual risk is modified by smoking and family history, which should be incorporated within the counseling process prior to treatment. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/efeitos adversos , Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Doenças Autoimunes/induzido quimicamente , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Idoso , Alemtuzumab , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados , Autoanticorpos/análise , Doenças Autoimunes/genética , Estudos de Coortes , Aconselhamento , Feminino , Seguimentos , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fumar , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/imunologia , Resultado do Tratamento , Adulto JovemAssuntos
Diabetes Insípido/etiologia , Transplante de Coração/efeitos adversos , Hipopituitarismo/etiologia , Linfoma de Células B/etiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diabetes Insípido/diagnóstico , Diabetes Insípido/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Therapy-related acute leukaemia (TRAL) is a concern for neurologists and patients when considering treatment with Mitoxantrone for multiple sclerosis (MS). The timing of this complication, risk, mortality and relationship to exposure remain uncertain. METHODS: We searched literature for publications relating to Mitoxantrone in MS, reviewed publication references and handsearched abstract lists to identify case-series reporting follow-up and complications of treatment with Mitoxantrone. We combined this with our local database of 250 cases treated since 1997. We also identified all reported individual cases of TRAL and extracted data reporting exposure (dose or mg/m(2)), timing and outcome of TRAL. RESULTS: Case-series including 5472 patients were identified; mean dose of Mitoxantrone was 74.2 mg/m(2) (range:12-120 mg/m(2)). TRAL was diagnosed in 0.30% (1 in 333). In 34 TRAL cases, sufficient data was available to inform analysis of exposure. Onset was a median of 18.5 months following Mitoxantrone treatment (range:4-60). Acute Myelocytic Leukaemia and Acute Promyelocytic Leukaemia represented 46.4% each of the leukaemia subtypes. Six of 25 TRAL patients, where outcome was reported, died (24%). Over 80% of cases occurred in patients exposed to >60 mg/m(2), with a relative risk of 1.44 (CI95%:1.18-1.70) when comparing total dose >60 mg/m(2) against <60 mg/m(2) strongly suggesting a relationship between risk of TRAL and total dose.
Assuntos
Antineoplásicos/efeitos adversos , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/epidemiologia , Mitoxantrona/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Doença Aguda , Adulto , Bases de Dados Factuais , Feminino , Humanos , Leucemia Promielocítica Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Ultraviolet radiation (UVR) may contribute to multiple sclerosis (MS) outcome by a mechanism involving vitamin D and the vitamin D receptor (VDR). In 512 patients with MS duration of 10 or more years, we studied the association of VDR single nucleotide polymorphisms (A/G(1229), C/G(3444), G/A(3944), CC(20965), CC(30056), F/f(30875), C/T(48200), T/t(65013)) with outcome or disability. ff(30875) frequency was lower in cases with EDSS > or = 6.0 than with scores < 6.0 (odds ratio = 0.38, 95% CI = 0.20-0.70). The association of ff(30875) with outcome was not mediated by cumulative exposure to UVR as assessed by questionnaire; low exposure (odds ratio = 0.42, 95% CI = 0.14-1.34) and high exposure (odds ratio = 0.34, 95% CI = 0.16-0.73).