Case Of Neuromyelitis Optica Research Articles

Absence of cortical demyelination in neuromyelitis optica

To asses the presence of cortical demyelination in brains of patients with neuromyelitis optica (NMO). NMO is an autoimmune inflammatory demyelinating disease that specifically targets aquaporin-4-rich regions of the CNS. Since aquaporin-4 is highly expressed in normal cortex, we anticipated that cortical demyelination may occur in NMO. This is a cross-sectional neuropathologic study performed on archival forebrain and cerebellar tissue sections from 19 autopsied patients with a clinically and/or pathologically confirmed NMO spectrum disorder. Detailed immunohistochemical analyses of 19 archival NMO cases revealed preservation of aquaporin-4 in a normal distribution within cerebral and cerebellar cortices, and no evidence of cortical demyelination. This study provides a plausible explanation for the absence of a secondary progressive clinical course in NMO and shows that cognitive and cortical neuroimaging abnormalities previously reported in NMO cannot be attributed to cortical demyelination. Lack of cortical demyelination is another characteristic that further distinguishes NMO from MS.

Multiple organ injury associated with neuromyelitis optica spectrum disorder in a low-grade B-cell lymphoma suspected of being follicular lymphoma

A 57-year-old woman was admitted to our hospital because she developed progressive paresthesia in the chest, lower limb weakness, and pain and swelling of the femoral region. Magnetic resonance imaging (MRI) of the spinal cord showed longitudinally extended transverse myelitis and a T2-hyperintense lesion extending from C5 to T4 (Fig. 1a). Brain MRI showed T2-hyperintense lesions predominantly in periventricular white matter, and corona radiata (Fig. 1b). MRI of the thighs showed T2-hyperintense lesions with hematomas in the rectus femoris muscles bilaterally associated with severe edema (Fig. 1c). Computed tomography showed no lymphadenopathy. The results of blood analysis were as follows: white blood cell count, 15.25 9 10/l (38.5% abnormal small cleaved lymphoid cells with inconspicuous nucleoli); creatine kinase, 2156 U/l; and C-reactive protein, 2.10 mg/dl. Serum NMO immunoglobulin G (NMO-IgG) (often called anti-aquaporin-4 [AQP4] antibody [AQP4-Ab]) was 3.8 U/ ml (normal \1.0 U/ml). A bone marrow aspirate showed an abnormal lymphoid infiltration of 32.6%. Immunohistochemical analysis showed that the cells were positive for CD10, CD20, and bcl-2. Southern-blot analysis showed clonal rearrangement of the immunoglobulin heavy-chain gene. We diagnosed her as a case of neuromyelitis optica (NMO) spectrum disorder [1] and AQP4-Ab–associated hematoma in rectus femoris bilaterally. We suspected follicular lymphoma but could not locate the primary site. Therefore, we also diagnosed low-grade B-cell lymphoma that was highly suspected of being follicular lymphoma. Methylprednisolone (1,000 mg/day) was administered intravenously, and was followed by a reduced dose of betamethasone (2 mg/day). However, a few days later, progressive paresthesia and leg weakness reappeared and she was diagnosed as a case of NMO spectrum disorder. Moreover, the patient’s serum sodium level had decreased to 127 mEq/l (normal 135–148 mEq/l), plasma osmolarity was 265 mOsm/kg/H2O (normal 285–295 mOsm/kg/H2O), while the urine osmolarity was 906 mOsm/kg/H2O. Plasma antidiuretic hormone (ADH) concentration was 8.3 pg/ml (normal 1.3–4.1 pg/ml). The patient was diagnosed with AQP4-Ab–associated syndrome of inappropriate secretion of ADH (SIADH). The NMO spectrum disorder was controlled by increasing the methylprednisolone dose to 125 mg/day followed by reducing the dose to 60 mg/day. Two weeks later, cough and dyspnea developed and the blood gas values showed a deteriorated condition. Chest radiograph revealed marked infiltrative shadows in bilateral lung fields (Fig. 1d). The clinical course and findings led to the diagnosis of AQP4-Ab-associated adult respiratory distress syndrome (ARDS). Methylprednisolone (1,000 mg/day) was administered, after which methylprednisolone was tapered off. Four days later, improvement of infiltrative shadows was observed on chest radiographs S. Nakayama-Ichiyama (&) T. Yokote N. Hiraoka K. Iwaki A. Takayama K. Kobayashi T. Akioka S. Oka T. Miyoshi S. Ishida T. Hanafusa Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka 569-0801, Japan e-mail: 1304@poh.osaka-med.ac.jp

Anti-Aquaporin-4 Antibody-Positive Optic Neuritis Treated with Double-Filtration Plasmapheresis

The anti-aquaporin-4 (AQP4) antibody was recently reported to be associated with neuromyelitis optica (NMO). Optic nerve involvements in many NMO cases are bilateral and the prognosis is poor. However, it has been suggested that plasma exchange is effective for those patients when steroid pulse therapy is ineffective. Herein, we report successful treatment of a patient with NMO using double-filtration plasmapheresis (DFPP). A 22-year-old woman consulted a neurologist for neck pain in March 2008. High-intensity lesions were shown in the cervical spinal cord by T2-weighted magnetic resonance imaging. On July 15, the patient was referred to our department for a headache and pain and blurred vision in the left eye. The best-corrected visual acuity was 20/50 and 20/500 in the right and left eyes, respectively, with visual field defects observed in both. After 3 courses of steroid pulse therapy, anti-AQP4 antibodies were positive. In November, the patient again noticed visual acuity loss in the left eye and was treated by additional steroid pulse therapy, which was not effective. Next, she underwent plasma exchange therapy, though it was stopped due to hypotension and dyspnea. The next day, the patient underwent DFPP treatment and visual function gradually recovered. It is important to consider NMO when steroid pulse therapy is not effective. We successfully and safely treated NMO in a young adult patient using DFPP.

A case of neuromyelitis optica developing into myelitis 25 years after optic neuritis

A case of neuromyelitis optica developing into myelitis 25 years after optic neuritis

Syndrome de Goujerot-Sjögren primitif et neuromyélite optique de Devic

Neuromyelitis optica (NMO) is characterized by the association of optic neuritis and myelitis without any other neurological signs. In 30% of the cases, NMO is associated with a systemic disorders. We report two cases of NMO associated with primary Sjögren's syndrome that was diagnosed during an acute flare of NMO. The relationship between NMO and Sjögren's syndrome has not been clearly identified. This association likely reflects the coexistence of two autoimmune disorders. The prognosis of NMO appears to be more severe in patients having coexisting Sjögren's syndrome, which renders useful to search for this association in patients with neuromyelitis optica.

Neuromyelitis optica and opticospinal multiple sclerosis: Mechanisms and pathogenesis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. In Asians, MS is rare; however, when it appears, the selective and severe involvement of the optic nerves and spinal cord is characteristic. This form, termed opticospinal MS (OSMS), has similar features to the relapsing form of NMO in Western populations. Recently, a specific IgG against NMO, designated NMO-IgG, was discovered, and the relevant antigen was found to be aquaporin-4 (AQP4), one of the major water channel proteins in the CNS. Because NMO-IgG has been reported to be present in 30–60% of OSMS patients, OSMS in Asians has been suggested to be the same entity as NMO. The sensitivity of NMO-IgG/anti-AQP4 antibody for NMO varies from 30% to 80%, while the specificity is 90–100%. Pathological studies on NMO have revealed perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions, where myelin basic protein (MBP) staining was relatively preserved. IgG from NMO-IgG-seropositive NMO patients induces astrocyte death in culture in the presence of complements, and reproduces astrocyte loss in vivo when MBP-specific T cells are co-transferred to cause experimental autoimmune encephalomyelitis. It is thus postulated that the complement-activating anti-AQP4 antibody plays a pivotal role in the development of NMO lesions through astrocyte necrosis, and that demyelination is a secondary event. However, in autopsied cases of NMO, we and others found that some demonstrated selective AQP4 loss while others showed preservation of AQP4, even in the acute lesions. We also found that, in some MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. In the CSF, proinflammatory cytokines such as IL-17, IL-8, IFNγ, and G-CSF are markedly elevated in OSMS patients, irrespective of the presence or absence of anti-AQP4 antibody. In OSMS and NMO patients, T cells reactive to myelin proteins show intra- and inter-molecular epitope spreading, suggesting that T cells are already stimulated with myelin antigens in vivo. These findings suggest that mechanism of NMO and OSMS in Asians is heterogeneous, anti-AQP4 antibody-related and -unrelated, and that not only anti-AQP4 antibody but also myelin-autoreactive Th17 or Th1 cells may also play a role in triggering CNS inflammation. Possible mechanisms for NMO and OSMS are discussed in this review.

Neuromyelitis optica preceded by hyperCKemia episode

Neuromyelitis optica (NMO) is a disease of the CNS characterized by severe optic neuritis and longitudinally extended transverse myelitis. Recent studies suggest that anti-aquaporin-4 (AQP4) antibodies, NMO-specific biomarkers, are pathogenic and target AQP4-expressing astrocytes in NMO, although an additional event (T-cell response or infection) should occur for anti-AQP4 antibodies and complements to pass through the blood-brain barrier and cause the CNS lesions. AQP4 is the major water channel in the CNS, but it is also expressed in fast-twitch skeletal muscle fibers. However, muscle diseases have not been described in NMO. We retrospectively examined the serologic database of 733 cases of NMO with anti-AQP4 antibody at the Department of Neurology, Tohoku University School of Medicine. The serum samples were sent to our laboratory for testing anti-AQP4 antibody from around the country during the period from 2006 to 2009. We found 3 anti-AQP4 antibody-positive female patients (7, 34, and 67 years old) with NMO who had episodes of prominent hyperCKemia (12,520, 19,415, and 59,660 IU/L) with general fatigue some weeks before the onset of optic neuritis. HyperCKemia was transient without any treatment in all patients, but recurred once in one of them. These cases suggest that hyperCKemia may be involved in the pathogenesis of neuromyelitis optica (NMO) in a fraction of patients. The causes of transient hyperCKemia are unknown. Further studies are needed to know the frequency of hyperCKemia in NMO and clarify its pathogenic role.

Neuromyelitis Optica

Neuromyelitis optica (NMO) or Devic's disease typically involves the optic nerves and the spinal cord and is most often relapsing. The pathogenesis is one of an acute inflammatory process targeting astrocytes and resulting in demyelination, as well as axonal injury. In a high proportion of recognized cases of NMO, there is a highly specific autoantibody (NMO-IgG), which is directed to the common central nervous system water channel, aquaporin-4. NMO attacks usually result in severe residual visual impairment or myelopathy. Despite the publication of new diagnostic criteria for NMO, uncertainty at the time of the index event as to whether the attack is due to multiple sclerosis or NMO can cause therapeutic hesitancy. Nevertheless, whenever a reasonable degree of suspicion exists, therapies directed to limiting acute injury and to preventing subsequent further injury mediated by humoral mechanisms should be instituted immediately. Investigations can then be completed and the therapeutic direction confirmed.For an acute attack, high-dose methylprednisolone and plasma exchange (generally given sequentially) are most useful.For the prevention of further attacks, selective or nonselective immunosuppressive therapy directed to humoral mechanisms is preferred. Agents recommended are oral azathioprine or mycophenolate mofetil with or without low-dose prednisolone or rituximab. Therapy should be planned to continue for up to 5 years in all patients, including those with a single attack who are at high risk of further relapse.Regrettably, there are no controlled trials for the treatment of either the classic manifestations of NMO or the so-called limited manifestations known as NMO spectrum disorders. The therapeutic opinions expressed in this article are therefore based on the current understanding of the pathogenesis of this disorder, reports of small series of patients receiving a range of treatments, and expert opinions.

Characteristic linear lesions and longitudinally extensive spinal cord lesions in Chinese patients with neuromyelitis optica

ObjectiveTo investigate the characteristics of the linear lesions and longitudinally extensive spinal cord (LESC) lesions in Chinese patients with neuromyelitis optica (NMO). MethodsThe medical records and magnetic resonance imaging (MRI) scans of 29 patients with NMO were reviewed. The frequencies and distributions of linear and LESC lesions were compared against those displayed by 22 multiple sclerosis (MS) patients. Furthermore, the association of lesions with aquaporin-4 IgG (AQP4-IgG) antibody was investigated. ResultsThe NMO patients had significantly more linear lesions than MS patients (48.3 vs 0%, p<0.001). In the NMO group, linear lesions were found in the medulla in 34.5% (10/29) of patients, across the medullospinal region in 10.3% (3/29) and in the spinal cord in 13.8% (4/29). LESC lesions can be seen more frequently in NMO than MS (72.4 vs 22.7%, p<0.001). In 93.1% (27/29) of the NMO cases, the axial section of the spinal MRI showed lesions on the central gray matter only, whilst the spinal lesions in MS were usually located in the peripheral white matter (72.7%, 16/22). The AQP4-IgG antibody was found to be associated with both linear and LESC lesions in NMO cases. ConclusionsHigh frequency of linear lesions and LESC lesions were found in Chinese patients with NMO and linear lesions were correlated with AQP4-IgG antibody.

Recent progress in multiple sclerosis research: astrocytopathy in demyelinating diseases

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. Recently, a specific IgG against NMO, designated NMO-IgG, was discovered, and the relevant antigen was found to be aquaporin 4 (AQP4), one of the major water channel proteins in the CNS. The sensitivity of NMO-IgG/anti-AQP4 antibodies for NMO varies from 30% to 80%, while specificity is 90-100%. Pathological studies on NMO patients have revealed perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions, while myelin basic protein (MBP) staining was relatively preserved. IgG from NMO-IgG-seropositive NMO patients induces astrocyte death in culture in the presence of complement, and reproduces astrocyte loss in vivo when MBP-specific T cells are co-transferred to cause experimental autoimmune encephalomyelitis. Therefore, it is postulated that the complement-activating anti-AQP4 antibodies have a pivotal role in the development of NMO lesions through astrocyte necrosis, and that demyelination is a secondary event. Baló's disease is characterized by alternating rings of demyelination and preserved myelin. As additional MS-like lesions often coexist in Baló's cases, Baló's disease is regarded as a variant of MS. However, Baló's concentric rings are also observed in NMO cases and in Asian opticospinal MS patients in the cerebral white matter, spinal cord and optic chiasm. In demyelinated areas, many hypertrophic astrocytes are present, in close contact with oligodendrocytes that often show apoptotic features. In the outermost layer of preserved myelin, stress proteins involved in tissue preconditioning are abundant in oligodendrocytes. The peri-plaque white matter is thus assumed resistant to subsequent attack, thereby leaving a layer of preserved myelin. In some patients, Baló's concentric rings develop systematically in a centrifugal direction, while other patients show simultaneous enhancement of multiple rings. Therefore, tissue preconditioning and successive ring formation does not fully explain the mechanism of the disease. We recently reported that AQP4 was extensively lost in glial fibrillary acidic protein-positive hypertrophic astrocytes, both in demyelinated and myelinated layers of all actively demyelinating lesions in four Filipino Baló's patients. None of six other patients with magnetic resonance imaging-confirmed Baló's disease was seropositive for anti-AQP4 antibodies. I therefore propose that AQP4 astrocytopathy, in the absence of anti-AQP4 antibodies, is characteristic of Baló's disease. Since a similar loss of AQP4 without perivascular deposition of immunoglobulin and complement is also observed in autopsied CNS tissues from NMO and MS cases, I consider that autoantibody-independent astrocytopathy may widely occur in human CNS demyelinating diseases, including Baló's disease, MS and NMO.

The challenge of acute non-compressive transverse myelopathies

The challenge of acute non-compressive transverse myelopathies

Neuromielitis óptica: actualización clínica

Neuromyelitis optica (NMO) or Devic's disease is an autoimmune, inflammatory and demyelinating central nervous system disorder that affects mainly to optic nerve and spinal cord. Recent advances have substantially permitted to expand the knowledge about this entity. To present a clinical update on the current understanding of the nature, progression, diagnosis and treatment of NMO. Due to its demyelinating nature and its recurrent behavior in most cases, NMO was first considered a form of multiple sclerosis (MS). However, recent findings have led to the conclusion that NMO is a distinct disorder, presenting important immunopathological, clinical, prognostic and therapeutic differences from MS. Fundamental in the under-standing of the disease was the recent discovery of antibodies directed against aquaporin-4 (anti-AQP4, also known as NMO-IgG), which are present in the majority of NMO cases clinically defined, and in a minority of patients with MS. Despite the knowledge on its immunopathogenesis and advances in diagnosis, the treatment of NMO is still challenging. NMO is a demyelinating disease different from MS. Current diagnostic criteria have been enriched with the recent description of the humoral disorder underlying NMO. However, current treatment options for NMO are far from being ideal.

The borderland of neuromyelitis optica

Neuromyelitis optica (NMO), also known as Devic’s disease, is an emerging clinical and pathological entity originally thought to be a variant of multiple sclerosis. Characterised by episodes of demyelination confined...

Neuromyelitis optica: current concepts and prospects for future management

To present an overview on the clinical manifestations and an update on the current management of neuromyelitis optica (NMO). NMO is associated with a significant risk of neurological, ocular and systemic morbidity. Many cases of NMO assume a relapsing course, which can lead clinicians to mistake the disease for multiple sclerosis. Distinguishing between the two diseases can be accomplished by recognizing the differences in clinical manifestations, observing the clinical course, obtaining serological testing and appreciating the MRI features. It is also important to maintain a high index of suspicion for NMO in the appropriate clinical setting. Clinical features of NMO include visual loss, decreased coordination, widespread asthenia, paraplegia, quadriplegia, and sensory impairment. Severe cases can result in bladder and bowel impairment or fatal respiratory failure. Symptomatic treatment and the currently available therapeutic agents can control the disease in many patients. However, given the lack of a curative treatment, the prognosis of NMO remains poor in some patients underscoring the need for drug development and controlled clinical trials focused on improved treatment strategies.

Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

BackgroundNeuromyelitis optica (NMO) is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably.Case PresentationWe report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM), having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling.ConclusionIn this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

PO10-TU-36 A case of neuromyelitis optica, improved by treatment with plasmapheresis

PO10-TU-36 A case of neuromyelitis optica, improved by treatment with plasmapheresis

Association of anti-aquaporin-4 antibody-positive neuromyelitis optica with myasthenia gravis

We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed.

A case of neuromyelitis optica (Devic's disease)

The Galle Medical Journal is published by the Galle Medical Association. The journal is published quarterly in March, June, September and December each year. The submissions are accepted throughout the year. The aims of the Journal are to foster co-operation among the medical fraternity and to be a forum to make literary contributions, share experiences encountered in medical practice, update their knowledge and have debates on topics related to all aspects of medicine.

A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended transverse myelitis (LETM). The clinical and laboratory features of NMO are different from multiple sclerosis (MS).1 An autoantibody to aquaporin-4 (AQP4) has been detected exclusively in the NMO sera.1 Moreover, we demonstrated an extensive loss of AQP4 and glial fibrillary acidic protein immunoreactivities in the perivascular regions with complement and immunoglobulin deposition in NMO that suggests astrocytic impairment. However, when AQP4 antibody is produced in patients with NMO is unknown, and thus it remains unresolved whether there are long-term asymptomatic AQP4 antibody–positive carriers, whether AQP4 antibody alone can be pathogenic, and whether AQP4 antibody is produced secondarily as a result of tissue destruction in attacks of NMO. We herein report a case of NMO in which AQP4 antibody was detected years before the NMO onset. ### Case report. A 34-year-old healthy woman without previous history of inflammatory or neurologic diseases noticed temporary skin eruptions on her chest and shoulders in June 2007. A dermatologist made the diagnosis of eczema. Three weeks later, when the skin eruptions subsided, she noted progressive paresthesia in the chest and toes. Within a few days, she could not walk well due to right leg weakness, and then she was hospitalized. Neurologic examination on …

Narcolepsy as an initial manifestation of neuromyelitis optica with antiaquaporin-4 antibody

JO N 3139 brospinal fluid (CSF) hypocretin level is useful for a diagnosis of narcolepsy [3]. The symptoms of narcolepsy are also known to occur secondary to hypothalamic lesions of various neurological conditions, such as brain tumors [6] and multiple sclerosis (MS) [2, 9]. Neuromyelitis optica (NMO) is a demyelinating disease typically manifesting transverse myelitis and bilateral optic neuritis. Anti-aquaporin-4 (AQP4) antibody was discovered as a disease-specific autoantibody in NMO patients [5]. Recently, brain lesions of NMO have been identified by many investigators and it has been reported that the lesions are generally observed in the hypothalamic region [7, 10]. In this paper, we report a case of NMO with anti-AQP4 antibody, whose initial manifestation was narcolepsy and marked decrease of CSF hypocretin level. A 35-year-old woman was referred for evaluation of excessive daytime sleepiness. On examination, apart from excessive daytime sleepiness, no neurological deficit was detected. She had no episode of cataplexy. A MRI scan showed a nonenhancing T2 lesion in the hypothalamus (Fig. 1 A). CSF study showed a slight degree of pleocytosis (12/mm3) and a normal protein level (23 mg/dl). The CSF hypocretin-1 level was markedly decreased (91 pg/ml; normal 200–350 pg/ml). She had narcolepsy-associated HLA haplotypes such as DR2 [3], but the DNA haplotypes were not typical for this disease (DRB1*1502, DQB1*0301, and DQB1*0601). Her sleep pattern was evaluated by nocturnal polysomnography (PSG) and multiple sleep latency test (MSLT). Her sleep latency was less than 10 min with SOREMP and total sleep time was 9.5 hours in PSG. The mean sleep latency by MSLT (4 naps) was 6 min with 4 SOREMPs. She was diagnosed as having narcolepsy due to Toru Baba Ichiro Nakashima Takashi Kanbayashi Masatoshi Konno Toshiyuki Takahashi Kazuo Fujihara Tatsuro Misu Atsushi Takeda Yusei Shiga Hiromasa Ogawa Yasuto Itoyama