Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

https://n.neurology.org/content/neurology/85/2/177.full.pdf

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

Background: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS) However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions Furthermore, some patients are misclassified as NMO by the authors’ earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS A serum autoantibody marker, NMO-IgG, is highly specific for NMO The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status Methods: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model Results: Fourteen patients with NMO (146%) had extra-optic-spinal CNS symptoms NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity Conclusions: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity CNS involvement beyond the optic nerves and spinal cord is compatible with NMO

https://n.neurology.org/content/neurology/66/10/1485.full.pdf

Revised diagnostic criteria for neuromyelitis optica

Summary Neuromyelitis optica (also known as Devic's disease) is an idiopathic, severe, demyelinating disease of the central nervous system that preferentially affects the optic nerve and spinal cord. Neuromyelitis optica has a worldwide distribution, poor prognosis, and has long been thought of as a variant of multiple sclerosis; however, clinical, laboratory, immunological, and pathological characteristics that distinguish it from multiple sclerosis are now recognised. The presence of a highly specific serum autoantibody marker (NMO-IgG) further differentiates neuromyelitis optica from multiple sclerosis and has helped to define a neuromyelitis optica spectrum of disorders. NMO-IgG reacts with the water channel aquaporin 4. Data suggest that autoantibodies to aquaporin 4 derived from peripheral B cells cause the activation of complement, inflammatory demyelination, and necrosis that is seen in neuromyelitis optica. The knowledge gained from further assessment of the exact role of NMO-IgG in the pathogenesis of neuromyelitis optica will provide a foundation for rational therapeutic trials for this rapidly disabling disease.

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The spectrum of neuromyelitis optica

Background Neuromyelitis optica (NMO) is a severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of blindness and paralysis. Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered patients with a well-established diagnosis of NMO in whom either asymptomatic or symptomatic brain lesions develop suggesting that the diagnostic criteria for NMO should be revised. Objective To describe the magnetic resonance image (MRI) brain findings in NMO. Design Observational, retrospective case series. Patients We ascertained patients through a clinical biospecimens database of individuals with definite or suspected NMO. We included patients who (1) satisfied the 1999 criteria of Wingerchuk et al for NMO except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate NMO from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. Main Outcome Measures Magnetic resonance images were classified as normal or as abnormal with either nonspecific, multiple sclerosis–like or atypical abnormalities. We evaluated whether brain lesions were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. Results Sixty patients (53 women [88%]) fulfilled these inclusion criteria. The mean ± SD age at onset was 37.2 ± 18.4 years and the mean ± SD duration of follow-up was 6.0 ± 5.6 years. Neuromyelitis optica–IgG was detected in 41 patients (68%). Brain MRI lesions were detected in 36 patients (60%). Most were nonspecific, but 6 patients (10%) had multiple sclerosis–like lesions, usually asymptomatic. Another 5 patients (8%), mostly children, had diencephalic, brainstem or cerebral lesions, atypical for multiple sclerosis. When present, symptoms of brain involvement were subtle, except in 1 patient who was comatose and had large cerebral lesions. Conclusions Asymptomatic brain lesions are common in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These observations justify revision of diagnostic criteria for NMO to allow for brain involvement.

https://jamanetwork.com/journals/jamaneurology/articlepdf/790890/noc50329.pdf

Brain abnormalities in neuromyelitis optica.

Background Neuromyelitis optica (NMO)–IgG is a specific autoantibody marker for NMO. It binds selectively to aquaporin 4 (AQP4), which is highly concentrated in astrocytic foot processes at the blood-brain barrier and is not restricted to optic nerve and spinal cord. Although it is conventionally believed that the brain is spared, brain imaging abnormalities are not uncommon in patients with NMO. Objective To investigate the location of brain lesions that are distinctive for NMO with respect to the localization of AQP4 in mammalian brain. Design Observational, retrospective case series. Setting Clinical serologic cohort of patients tested for NMO-IgG for whom brain MRI images were available. Patients We identified 120 patients seropositive for NMO-IgG for whom brain magnetic resonance images were available. Main Outcome Measure Magnetic resonance imaging abnormalities. Results In 8 patients we observed recurring and distinctive magnetic resonance imaging abnormalities in the hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. Conclusion The distribution of NMO-characteristic brain lesions corresponds to sites of high AQP4 expression.

https://jamanetwork.com/journals/jamaneurology/articlepdf/791822/noc60039.pdf

Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.

We describe two cases of neuromyelitis optica (NMO) with clinical and radiographically confirmed features of hypothalamic involvement, in the absence of other parenchymal brain lesions. Their course is otherwise typical of Devic's form of NMO. A review of the literature identifies additional cases of NMO in which clinical features attributable to under-recognized dysfunction of the hypothalamic-pituitary axis were present. We propose that the currently accepted criteria for the diagnosis of NMO could be revisited to recognize the possibility of lesions developing within hypothalamic structures.

Neuromyelitis optica with hypothalamic involvement.

The goal of this study was to determine if certain imaging features suggest the diagnosis of cerebellar medulloblastoma in adults and to determine how often the classic CT appearance seen in children is present in adults. The study included 28 adult patients with proved cerebellar medulloblastoma. The tumor was located in the cerebellar vermis in 14 patients and in a cerebellar hemisphere in 14 patients. Thirteen patients had unenhanced CT of the brain, all patients had contrast-enhanced CT, and eight patients had unenhanced MR imaging. The imaging features in adults were compared with those in children, as described in the literature. In our adult patients, all tumors were hyperdense compared with gray matter on unenhanced CT and showed a slight to moderate increase in density after injection of contrast medium. Thirteen lesions had well-defined margins, and 15 had poorly defined margins. Low-density areas consistent with cystic and necrotic degeneration were detected in 23 (82%) of the 28 tumors. By comparison, in children, medulloblastoma usually originates in the vermis. As in adults, the mass is hyperdense on unenhanced CT, but enhances markedly and homogeneously after injection of contrast medium. Usually no evidence of cyst formation or necrosis is seen, and the tumor margins are well defined. This classic CT appearance of medulloblastoma in children was identified in only three (11%) of the 28 adult patients. Medulloblastoma has a variable MR appearance in both children and adults. On T2-weighted images, lesions are hypo-, iso-, or hyperintense compared with normal gray matter. The CT findings of medulloblastoma in adults usually differ from those of medulloblastoma in children. The tumor has a variable and nonspecific appearance in adults and should always be considered in the differential diagnosis of a mass in the posterior fossa.

CT and MR imaging findings in adults with cerebellar medulloblastoma: comparison with findings in children

We describe our technique and results of dynamic, reconstructed, three-dimensional (3-D computed tomographic (CT) angiography in our first 18 patients with either complex aneurysms, producing subarachnoid hemorrhage or the compression of neighboring structures, or small asymptomatic aneurysms, and assess the role of this technique in treatment planning. A dynamic, infused CT scan producing 1.5-mm cuts of the area of interest was performed, and the two-dimensional images were reconstructed in three dimensions with the ISG Allegro system (ISG Technologies, Toronto, Ontario, Canada). Results were compared with intra-arterial digital subtraction angiography and magnetic resonance angiography. All aneurysms over 3 mm and half of the aneurysms less than or equal to 3 mm were demonstrated by 3-D CT angiography. The neck of the aneurysm, its relationship to the parent artery and associated branches, and its relationship to surrounding bony structures, such as the anterior clinoid, were also demonstrated. This was especially useful for ophthalmic aneurysms. The 3-D image could be rotated on the screen to mimic the operative approach. The active, filling portion and the thrombosed part of partially thrombosed, giant aneurysms could be seen on the same image, and the active, filling portion could be better appreciated with 3-D CT angiography than with magnetic resonance angiography. A partially treated, acrylic-coated aneurysm that could not be completely assessed otherwise has been demonstrated by this technique. 3-D CT angiography is useful in the evaluation of aneurysms, especially when the local anatomy is obscured or distorted by its mass or by the anterior clinoid. It was superior to magnetic resonance angiography in demonstrating the actively filling and thrombosed portions of giant, partially thrombosed aneurysms and is useful in planning the surgical approach. 3-D CT angiography may find a place in the assessment and treatment of complex aneurysms

Three-dimensional computed tomographic angiography of cerebral aneurysms.

Our purpose was to review the incidence of negative cerebral panangiography in acute nontraumatic subarachnoid haemorrhage (SAH); to document the amount and distribution of subarachnoid blood on CT and determine its relationship to findings on repeat angiography; and to study the outcome of these patients from the time of presentation to hospital discharge. From 1983 to 1992, 295 patients underwent cerebral angiography for acute SAH at our institution. The CT, angiographic and MRI findings and clinical course of patients with initially negative angiograms were reviewed retrospectively. The overall incidence of negative cerebral panangiography was 31% (92/295). An aneurysm was disclosed on a second angiogram in 4 cases, and on a third angiogram in 1, giving a total false negative rate of 5%. In 55% of cases, only a small amount of SAH was present on CT. The distribution of the subarachnoid blood was nonspecific and resembled the pattern seen in aneurysmal SAH. Ninetyfour percent, of the patients presented in Hunt-Hess grades I and II. The complications of conservative treatment were few: a rebleed rate of 4%, delayed cerebral ischemia in 4%, cerebral infarcts in 8% and hydrocephalus requiring shunting in 3%. On discharge, 93% of patients had recovered completely and the others were left with moderate disability. There were two deaths related to massive rebleeding. Patients with perimesencephalic SAH (35%) fared particularly well; none developed complications during their hospital stay and repeat angiograms never revealed an underlying aneurysm. In such cases, further angiographic investigations do not seem warranted.

The negative angiogram in subarachnoid haemorrhage.

A retrospective CT, MR, and histopathologic study was performed in five patients with histologically verified low-grade myxoid chondrosarcoma of the base of the skull. In four patients, the tumor originated off the midline and was associated with bone destruction at the petrous apex near the petrooccipital fissure. Tumor extent included the cerebellopontine angle in three patients and the parasellar area in two patients. The fifth tumor originated on the midline and was associated with destruction at the dorsum sellae. Three tumors contained calcifications, whereas two lesions were mostly isodense with brain on CT scan. All tumors were hypointense on T1-weighted MR images and very intense on T2-weighted images except for areas of signal void consistent with calcifications. Light microscopy revealed islands of mature hyaline cartilage in an abundant myxoid ground substance. Histology and immunocytochemical analysis were consistent with a low-grade myxoid chondrosarcoma. The CT and MR features of low-grade myxoid chondrosarcoma are comparable with those of chordoma. Chordoma usually arises from the midline, but cases with origin from the lateral portion of the clivus or the petrous apex have been described. Low-grade myxoid chondrosarcoma has distinct histologic and immunocytochemical features and includes lesions formerly called "chondroid chordomas."

D. Melançon

Papers

Neuromyelitis optica with hypothalamic involvement.

CT and MR imaging findings in adults with cerebellar medulloblastoma: comparison with findings in children

Three-dimensional computed tomographic angiography of cerebral aneurysms.

The negative angiogram in subarachnoid haemorrhage.

Low-grade myxoid chondrosarcoma of the base of the skull: CT, MR, and histopathology.