Neuritis ópticas desmielinizantes y autoinmunes / Autoimmune and demyelinating optic neuritis

El conocimiento sobre las neuropatías ópticas desmielinizantes y autoinmunes ha experimentado una revolución en la útima década tras el descubrimiento de los anticuerpos antiacuaporina 4 (AQP4). Las mejoras en las técnicas diagnósticas, el descubrimiento de nuevas dianas y el avance de la neuroinmunología han permitido la detección de anticuerpos asociados a las enfermedades desmielinizantes. Se presenta una revisión de los conceptos clásicos y nuevos de las neuritis ópticas desmielinizantes y autoimmunes. Se describe el debate en las constantes reformulaciones de su clasificación. Asimismo se actualizan los criterios diagnósticos de la esclerosis múltiple y de la neuromielitis óptica. Finalmente, se presentan los nuevos conceptos sobre las MOGopatías y las neuropatías opticas inflamatorias crónico-recurrentes (CRION)

The knowledge on demyelinating and autoimmune optic neuropathies has experienced a revolution the last decade since the discovery of anti-aquaporin 4 antibody. Improvements in diagnostic techniques, and the finding of new targets, along with advances in neuro-immunology have led to the detection of antibodies related to demyelinating diseases. A review is presented on the classical and new concepts in optic neuritis. The debate on the classification of demyelinating and autoimmune optic neuritis is presented. Furthermore, the updated diagnostic criteria in multiple sclerosis and neuro-myelitis optics are described. Finally, the latest insights into Myelin Oligodendrocyte Glycoprotein (MOG) disorders and chronic-recurring optic neuropathies (CRION) are highlited

Relapsing optic neuritis: a multicentre study of 62 patients.

BACKGROUND: Optic neuritis (ON) may be the first symptom of a central nervous system demyelinating, systemic or infectious disease but few patients experience recurrent episodes and have a negative workup. OBJECTIVE: This disorder, named relapsing optic neuritis (RON), is poorly described in the literature and still presents a particular challenge in diagnosis and management. METHODS: We describe the clinical, laboratory, magnetic resonance imaging (MRI) and disability course of RON in a French cohort of 62 patients, based on a multicentre, retrospective, observational study. RESULTS: In our cohort, we identified two distinct groups of RON patients. The first is characterised by relapsing inflammatory optic neuritis (RION, 68%), which is non-progressive, whereas the second presented as a chronic relapsing inflammatory optic neuritis (CRION, 32%), which is progressive. We have noted more cases with steroid dependence in the CRION group than the RION group (42% vs 10%). The long-term visual prognosis was more severe in CRION patients and neuromyelitis optica-immunoglobulin G (NMO-IgG)-positive patients. CONCLUSION: RON is likely a separate entity corresponding to an autoimmune disease that differs from multiple sclerosis (MS), NMO and vasculitis. We provide a new classification system based on a better understanding of RON which could allow an improved management by early treatment of poor prognosis forms.

Atypical forms of optic neuritis.

Inflammatory optic neuritis (ON) represents a frequent clinical situation in neurology and ophthalmology. The most current etiology is multiple sclerosis (MS) but, when MRI and Cerebrospinal fluid (CSF) analyses are normal, ON is usually considered as "idiopathic" with a suspected viral etiology. In rare cases, a systemic disease such as sarcoidosis, lupus or Sjögren syndrome may be diagnosed. In several cases either a recurrence or a myelitis may occur without any argument for MS. In the first case, it corresponds to relapsing inflammatory optic neuritis (RION) and in the second case to neuromyelitis optica (NMO). In the present paper, the author successively presents the various clinical situations and complementary findings (infectious, vasculitis, NMO or idiopathic) that can lead to a differential diagnosis of MS in a context of ON.

Immune-mediated CNS diseases: a review on nosological classification and clinical features.

The immune-mediated diseases of the central nervous system (CNS) cover a wide range of clinical manifestations. Over the last years, considerable efforts have been made to establish a nosologic concept based upon distinctive pathophysiological characteristics of the single diseases. We describe the historically defined entities of immune-mediated diseases that primarily, but not exclusively, are affecting myelin structures. These include very rare entities as Schilder's, Balo's and Marburg's disease or the chronic and relapsing types of optic neuritis, for which evidence based paradigms still are virtually missing. In other, slightly more frequent diseases as neuromyelitis optica (NMO), advances in the concepts of specific biological features have been achieved and are beginning to transform into changes in clinical concepts. Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are by far the most frequent entities in this group and thus the only ones for which extensive empirical data on disease biology and evidence based clinical management strategies exist by now. For the most important entities, clinical features and therapeutic approaches are reviewed on the basis of current evidence. The results of basic science studies are assessed for their implications in nosological classification.

Magnetic resonance imaging in acute optic neuritis in Singapore.

INTRODUCTION: The Optic Neuritis Treatment Trial (ONTT) has established that the magnetic resonance imaging (MRI) findings at the time of presentation of optic neuritis (ON) is the strongest indicator of the development of multiple sclerosis (MS). Reports from Singapore as well as other Asian countries have indicated that these abnormalities are less frequently encountered compared to that reported by the ONTT. This paper aims to describe systematically the brain MRI as well as the optic nerve abnormalities in patients after an episode of acute optic neuritis. MATERIALS AND METHODS: Patients who presented with acute optic neuritis were retrieved from our prospective optic neuritis study and their MRI scans were reviewed and graded in accordance with the standardised classification employed in the ONTT. RESULTS: Fifteen of 24 patients had MRI brain and optic nerves performed during the acute episode. In the evaluation of brain abnormalities, 40% were classified as grade 0, 20% grade I, 20% grade II, 6.7% grade III and 13.3% grade IV. Optic nerve abnormalities were observed in 80% of cases. At study entry, 10 patients had idiopathic (monosymptomatic) ON, 3 had multiple sclerosis (MS), one each with infective and autoimmune optic neuritis, respectively. The single patient who developed MS at study completion presented with grade II brain abnormalities at the initial MRI. For those with idiopathic ON, our study revealed a higher percentage of grade 0-I brain changes as well as a lower lesion load compared to the ONTT.Lesion Load and grade was also lower in anterior optic neuritis compared with retrobulbar disease. CONCLUSION: Our study revealed a lower percentage of grade II-IV brain MRI abnormalities as well as less lesion load in idiopathic ON compared to the ONTT. This may be related to the lower prevalence of MS in our predominantly Asian population. As diagnostic tests and understanding of neuromyelitis optica or Devic's disease improves, we may see more patients being diagnosed with this condition, which may also explain our findings. Our data also showed that MRI grade and lesion load in cases of anterior ON was lower than for retrobulbar disease. MRI in ON has an essential role in characterising the disease, evaluating for associated brain lesions, and assessing prognosis in retrobulbar disease but may be less useful in anterior disease.

[Quality of life in visual disturbances in multiple sclerosis]. / Jakosc zycia w zaburzeniach widzenia w stwardnieniu rozsianym.

In multiple sclerosis (MS) often the visual pathway is impaired. Very early symptom which precedes neurological signs is the retrobulbar optic neuritis. In MS patients near as well as distance, color and peripheral vision can be disturbed. Many patients are not aware of visual impairment which could cause the delay in diagnosis. The assessment of the visual field in patients with MS enables early diagnosing as well as monitoring of the course of the disease. In monitoring of the course of disease most important is the evaluation of quality of life. The assessment of quality of life in MS is well known, even better than in other neurological diseases. Less known is the question of quality of life diminished because of visual field defects in MS. In review report the value of perimetry in diagnosing MS, visual disturbances in MS and contemporary possibilities of evaluation of quality of life in MS patients including those with defects in visual field has been described. The VFQ-25 questionnaire is a sensitive and useful tool in self-assessing visual function in MS patients.

Transient 5-(4-phenylbutoxy)psoralen (PAP-1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles.

Discovery of treatments to protect axonal function of neurons and prevent permanent disability associated with progressive multiple sclerosis (MS) has faced the uphill challenge of assessing relatively small changes in accumulated axon damage within a background environment that is disorganized by CNS inflammation. We hypothesized that transient immunosuppression after initiation of MS-like autoimmune mechanisms would disassociate development of MS-like myelinated axon pathology from development of CNS inflammation in a rat model of autoimmune optic neuritis (AON). A rat model of myelin oligodendrocyte glycoprotein peptide-induced AON was transiently treated (on days 3-7 after antigen exposure) with 5-(4-phenylbutoxy)psoralen (PAP-1), an immunomodulatory drug previously shown specifically to suppress proliferation of effector memory T-cells and immunoglobulin class-switched B-cells. Thirteen days after antigen exposure, optic nerves were harvested for quantitative assessment of 12 MS-associated pathologies using microfluorimetry. With one exception, the immunoreactivities (-ir) for eight markers of MS-like neuroinflammation and immune infiltration were significantly reduced (P < 0.05) by transient PAP-1 treatment, often to levels significantly below those detected in normal control rat optic nerves. With one exception, four immunoreactive markers of MS-like myelinated axon pathology were detected at levels indicating increased axon/myelin pathology compared with vehicle-treated rats with AON (P < 0.05). These data suggest the conclusion that early causative mechanisms in CNS autoimmunity initiate signaling mechanisms that diverge into two separate pathways, one that is strongly associated with inflammatory responses and one that is associated predominantly with disturbed axon-myelin interactions and impaired fast axonal transport.

Optical coherence tomography and disease subtype in multiple sclerosis.

OBJECTIVE: To examine retinal nerve fiber layer (RNFL) thickness, macular volumes (MV), and visual acuity in multiple sclerosis (MS) eyes, with and without history of acute optic neuritis (ON). METHODS: RNFL thickness was measured in 326 MS and 94 control eyes using optical coherence tomography (OCT). MV and vision testing were done in a subset of the cohort. MS subtype was classified as relapsing-remitting (RRMS, n = 135), primary progressive (PPMS, n = 12), and secondary progressive (SPMS, n = 16). RESULTS: MS ON eyes had decreased RNFL thickness (84.2 microm) compared to controls (102.7 microm) (p < 0.0001). Unaffected fellow eyes of MS ON eyes (93.9 microm) (p < 0.01) and patients with MS with no history of ON (95.9 microm) (p < 0.05) also had decreased RNFL. RRMS (94.4 microm) (p < 0.001), PPMS (88.9 microm) (p < 0.01), and SPMS (81.8 microm) (p < 0.0001) (adjusted for age and duration of disease) had decreased RNFL compared to controls. There were significant differences in RNFL thickness within quadrants of peripapillary retina comparing relapsing to progressive MS subtypes. MV was decreased in MS ON eyes (6.2 mm(3)) (p < 0.0001) and SPMS subjects (6.2 mm(3)) (p < 0.05) compared to controls (6.8 mm(3)). CONCLUSION: Retinal nerve fiber layer (RNFL) is significantly decreased in multiple sclerosis (MS) optic neuritis (ON) eyes, unaffected fellow eyes of patients with MS ON, and MS eyes not affected by ON in our cohort. Macular volumes (MV) showed a significant decrease in MS ON eyes. Progressive MS cases showed more marked decreases in RNFL and MV than relapsing-remitting MS. OCT is a promising tool to detect subclinical changes in RNFL and MV in patients with MS and should be examined in longitudinal studies as a potential biomarker of retinal pathology in MS.

Prognosis of Taiwanese patients with isolated optic neuritis after intravenous methylprednisolone pulse therapy.

BACKGROUND/PURPOSE: To evaluate the clinical manifestations, prognosis, recurrence rate and development of multiple sclerosis between papillitis group and retrobulbar group in Taiwanese patients with isolated acute optic neuritis (AON) after treatment with intravenous methylprednisolone pulse therapy. METHODS: We retrospectively reviewed patients with AON who had received intravenous methylprednisolone pulse therapy. These patients were classified into retrobulbar or papillitis groups. Demographic characteristics, responsiveness to pulse therapy, recurrence rate and incidence of multiple sclerosis were compared between these two groups. RESULTS: Of the 43 patients enrolled in this study, 19 patients (44%) were in the retrobulbar group and 24 patients (56%) were in the papillitis group. Seven cases (16%) showed periventricular plaque on magnetic resonance imaging (MRI). Among these seven patients, five developed definite or probable multiple sclerosis. The incidence of multiple sclerosis in patients with positive brain MRI findings was significantly higher than in patients with negative MRI findings (p = 0.002). There was no statistical difference in final visual acuity between the two group (p = 0.353). Sixteen patients suffered from recurrence of AON (21% in the papillitis group and 58% in the retrobulbar group, p = 0.029). Two patients (8%) in the papillitis group and six patients (32%) in the retrobulbar group developed multiple sclerosis (p = 0.061) with a mean interval of 21.6 +/- 11.2 months. CONCLUSION: AON in Taiwan has a relatively lower percentage of development of multiple sclerosis than in Western countries. The presence of periventricular plaque on MRI is significantly associated with the later development of multiple sclerosis. The retrobulbar group had a stronger association with recurrence and development of multiple sclerosis.

Does high-field MR imaging have an influence on the classification of patients with clinically isolated syndromes according to current diagnostic mr imaging criteria for multiple sclerosis?

BACKGROUND AND PURPOSE: Current MR imaging criteria for multiple sclerosis (MS) do not specify the magnetic field strength. The aim of this study was to investigate whether different MR imaging field strengths, specifically high-field MR imaging, have an impact on the classification of patients with clinically isolated syndromes suggestive of MS, according to MR imaging and diagnostic criteria. METHODS: In a prospective intraindividual comparative study, we examined 40 patients with clinically isolated syndromes (CIS) consecutively with a 1.5 T and 3T MR imaging system, including axial sections of T2 turbo spin-echo, fluid-attenuated inversion recovery, and T1 spin-echo, before and after injection of gadolinium-diethylene-triaminepentaacetic acid. Constant resolution parameters were used for both field strengths. High-signal-intensity white matter lesions with a size of >3 mm were counted and categorized according to their anatomic location in infratentorial, callosal, juxtacortical, periventricular, and other white matter areas. Assessment of the fulfilled Barkhof MR imaging and McDonald diagnostic criteria was made separately for both field strengths in every patient. RESULTS: Eleven patients fulfilled more MR imaging criteria at 3T. Two of these patients fulfilled the criterion of dissemination in space (DIS) according to the first definition of McDonald criteria, which is based on imaging criteria alone. Another patient had DIS only at 3T, according to the second definition of the McDonald criteria including CSF parameters. CONCLUSION: MR field strength, specifically high-field MR imaging, has a substantial influence on the classification of patients with CIS according to imaging and a mild influence on the classification according diagnostic criteria for MS, leading to consequences for prognostic classification, imaging guidelines, and clinical trials.

Controversies in optic neuritis pain diagnosis.

Optic neuritis (ON) refers to any inflammatory disorder of the optic nerve. In clinical practice ON is mainly diagnosed by ophthalmologists and less frequently by neurologists. ON diagnostic criteria are included in different classification systems both in neurologic and ophthalmologic fields. Diagnosis of ON is still very unsatisfactory. Indeed diagnostic criteria are not uniform and therefore the diagnosis is still mainly formulated according to the clinical experience only. A consensus on practice guidelines for ON diagnosis might be useful. Ocular pain is a milestone in ON diagnosis, but it is too often mistreated by both the patient and the clinician. The International Headache Society (IHS) Classification of Headache Disorders provides in its 1988 and 2004 versions the diagnostic criteria for ON. These criteria are not spread and followed by the large majority of neurologists, but they are mainly applied by the experts in headache disorders. On the other hand, ON is a disorder widely encountered by neurologists and ophthalmologists. The latest IHS version defines the criteria of the pain features more precisely, but it is still unsatisfactory. In a future revision, the pain should be further detailed. Further studies aimed at validation of the diagnostic criteria of ON are strongly needed.

Optic neuritis: diagnostic criteria application in clinical practice.

Optic neuritis (ON) refers to any inflammatory optic neuropathy. In clinical practice ON is mainly diagnosed by ophthalmologists and less frequently by neurologists. ON diagnostic criteria are included in the Classification of International Headache Society (IHS) and in other classification systems, both in neurological and ophthalmologic fields. The aims of this study were to verify the application of IHS ON diagnostic criteria in clinical practice and the role of the ocular pain qualitative aspects. We performed a partially retrospective (140 cases) and prospective (43 cases) study analysing the clinical characteristics of patients with ON. We observed retro orbital pain in a huge percentage of patients; it was provoked or spontaneous and worsened by eye movements. We found that the new IHS classification criteria (IHS 2004) do not fully satisfy the requirements for ON diagnosis. Further study is necessary to validate the diagnostic criteria of ON in clinical practice.

[Course of illness and prognosis of multiple sclerosis. 2: Predictive value of clinical and paraclinical factors]. / Krankheitsverlauf und Prognose der multiplen Sklerose. 2. Teil: Prädiktiver Wert klinischer und paraklinischer Faktoren.

The second part of this review summarizes the predictive value of demographic factors, the early clinical course and paraclinical methods in the prognosis of multiple sclerosis (MS). The chronic progressive course is generally thought to be associated with a worse outcome compared to relapsing-remitting MS. Moderate disability within 5 years, residual pyramidal and cerebellar deficits 6 months following an acute attack, motor, cerebellar and possibly brain stem exacerbations as well as frequent relapses were found to indicate an increased risk for developing severe disability or increased mortality. Magnetic resonance imaging (MRI), evoked potentials and cerebrospinal fluid findings were not found to be predictive in clinically definite MS, although there was a weak association of MRI findings and disability. However, these paraclinical modalities were important methods to predict the further development of clinically isolated demyelinating syndromes. In this regard, MRI was identified as the strongest predictive factor of the conversion to definite MS.

Severe visual loss related to isolated peripapillary retinal and optic nerve head cytomegalovirus infection.

We examined ten patients from a consecutive series of 73 patients with either isolated cytomegalovirus papillitis or limited cytomegalovirus retinitis contiguous with the optic disk. Patients with peripheral retinitis and other areas of retinitis were excluded. All patients were treated with ganciclovir. Two distinct types of cytomegalovirus infection of the peripapillary area were identified. Type I was characterized by spread of limited retinitis to the optic disk margin, good central visual acuity, and permanent arcuate and altitudinal visual field defects that enlarged and became more complete as the retinitis progressed toward the disk. Type II appeared to be a true cytomegalovirus infection of the optic nerve characterized by primary, isolated papillitis with peripapillary retinitis, an early afferent pupillary defect, and good initial visual acuity, which rapidly deteriorated despite prompt antiviral therapy. Peripapillary cytomegalovirus retinitis appears to be an important and underreported cause of visual morbidity in patients with AIDS.