ABSTRACT
Myelitis and optic neuritis are prototypic clinical presentations of both multiple sclerosis and neuromyelitis optica. Once considered a subtype of multiple sclerosis, neuromyelitis optica, is now known to have a discrete pathogenesis in which antibodies to the water channel, aquaporin 4, play a critical role. Timely differentiation of neuromyelitis optica from MS is imperative, determining both prognosis and treatment strategy. Early, aggressive immunosuppression is required to prevent the accrual of severe disability in neuromyelitis optica; conversely, MS-specific therapies may exacerbate the disease. The diagnosis of neuromyelitis optica requires the integration of clinical, MR imaging, and laboratory data, but current criteria are insensitive and exclude patients with limited clinical syndromes. Failure to recognize the expanding spectrum of cerebral MR imaging patterns associated with aquaporin 4 antibody seropositivity adds to diagnostic uncertainty in some patients. We present the state of the art in conventional and nonconventional MR imaging in neuromyelitis optica and review the place of neuroimaging in the diagnosis, management, and research of the condition.
Subject(s)
Neuroimaging/methods , Neuromyelitis Optica/diagnosis , Humans , Neuroimaging/trendsABSTRACT
Eight patients with paraneoplastic cerebellar degeneration (PCD) and anti-Yo antibodies were investigated to determine whether there is any association between cytotoxic T lymphocyte (CTL) responses reactive with two previously defined Yo-derived, HLA-A2.1 restricted epitopes (cdr2-1 and cdr2-2) and the presence of tumour-infiltrating CD8+ CTLs. cdr2-1 and cdr2-2-specific CTL responses could not be detected in 5 HLA-A2.1(+) patients in an ex vivo interferon-gamma ELISPOT assay and only 2/9 tumour sections contained CD8(+) intratumoural lymphocytes suggesting a very limited role for CTL-mediated tumour immunity in this patient group, all of whom had evidence of widespread malignancy at the time of diagnosis and/or death.
Subject(s)
Antibodies, Neoplasm/blood , DNA-Binding Proteins/immunology , Interferon-gamma/analysis , Neoplasm Proteins/immunology , Paraneoplastic Cerebellar Degeneration/immunology , T-Lymphocytes, Cytotoxic/immunology , Breast Neoplasms/immunology , Cerebellar Neoplasms/immunology , Cytotoxicity Tests, Immunologic , Enzyme-Linked Immunosorbent Assay/methods , Epitopes, T-Lymphocyte/immunology , Female , HLA-A2 Antigen/immunology , Humans , Immunohistochemistry , Interferon-gamma/metabolism , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/chemistry , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Nerve Tissue Proteins/immunology , Ovarian Neoplasms/immunology , Paraneoplastic Cerebellar Degeneration/diagnosis , Paraneoplastic Cerebellar Degeneration/pathology , Protein Isoforms/immunology , Staining and Labeling , T-Lymphocytes, Cytotoxic/pathologyABSTRACT
The authors recruited 19 nonambulant patients with Guillain-Barré syndrome into a pilot, double-blind, randomized, placebo-controlled safety trial of interferon beta 1a (IFN[beta]-1a) (Rebif). Participants received IFN[beta]-1a or placebo subcutaneously three times weekly, 22 microg for the first week and then 44 microg for up to 24 weeks, in addition to IV immunoglobulin (IVIg). IFN[beta] did not have any unexpected interaction with IVIg and there was no significant difference in rate of improvement.
Subject(s)
Guillain-Barre Syndrome/drug therapy , Interferon-beta/therapeutic use , Recombinant Proteins/therapeutic use , Cytokines/blood , Disability Evaluation , Dose-Response Relationship, Drug , Fatigue/chemically induced , Female , Guillain-Barre Syndrome/immunology , Humans , Immunoglobulins, Intravenous/therapeutic use , Interferon beta-1a , Interferon-beta/adverse effects , Lymphopenia/chemically induced , Male , Middle Aged , Pilot Projects , Recombinant Proteins/adverse effects , Treatment OutcomeSubject(s)
Antigens, Neoplasm , Brain Stem/immunology , Neoplasm Recurrence, Local/complications , Nerve Tissue Proteins/immunology , Ocular Motility Disorders/immunology , Paraneoplastic Syndromes, Nervous System/immunology , RNA-Binding Proteins/immunology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Stem/pathology , Brain Stem/physiopathology , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/secondary , Female , Humans , Kidney Neoplasms/pathology , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/drug therapy , Nerve Tissue Proteins/blood , Neuro-Oncological Ventral Antigen , Ocular Motility Disorders/blood , Ocular Motility Disorders/physiopathology , Paraneoplastic Syndromes, Nervous System/blood , Paraneoplastic Syndromes, Nervous System/physiopathology , RNA-Binding Proteins/blood , Retroperitoneal Neoplasms/drug therapy , Retroperitoneal Neoplasms/secondary , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Although X-linked myotubular myopathy (XLMTM) is a recessive disorder, heterozygous female carriers of MTM1 mutations may present with limb girdle and facial weakness. It is proposed that manifesting heterozygote females with XLMTM have a skewed pattern of X-chromosome inactivation. However, skewed X-chromosome inactivation was not detected in either the lymphocyte or muscle DNA of a woman who presented with limb girdle/facial weakness and was found to be heterozygous for the R224X mutation.
Subject(s)
Genetic Carrier Screening , Genetic Linkage/genetics , Muscle Weakness/genetics , Myopathies, Structural, Congenital/genetics , Protein Tyrosine Phosphatases/genetics , X Chromosome/genetics , Adult , Dosage Compensation, Genetic , Extremities/pathology , Face/pathology , Female , Humans , Infant , Male , Muscle Weakness/pathology , Muscle, Skeletal/pathology , Mutation/genetics , Myopathies, Structural, Congenital/pathology , Pedigree , Protein Tyrosine Phosphatases, Non-ReceptorABSTRACT
Serum antibodies to the Yo antigen are usually associated with paraneoplastic cerebellar degeneration arising in female patients with gynecological or breast malignancy and are rarely associated with other tumors. We report a male patient who presented with paraneoplastic cerebellar degeneration and anti-Yo antibodies following removal of an esophageal adenocarcinoma. This is only the third report of anti-Yo antibodies occurring in a male patient. The Yo antigen was expressed by the esophageal tumor but not in a frontal lobe cerebral metastasis identified at postmortem. Interestingly, CD8+ T-cell infiltration was also found in the tumor, but not in the metastasis, consistent with down-regulation of Yo expression by the tumor cells leading to evasion from immune-mediated tumor surveillance.