Tumefactive demyelination and glioblastoma: a rare collision lesion.

OBJECTIVE: Inflammatory demyelination occasionally forms a solitary mass lesion clinically and radiographically indistinguishable from glioma, replete with enhancement and mass effect. Termed "tumefactive demyelination" it often prompts a brain biopsy. DESIGN: We undertook neuroimaging and morphologic analysis of a unifocal demyelinating lesion intimately associated with glioblastoma. MRI characteristics of the lesion were assessed as were biopsy and resection specimens by both histological and immunohistochemical methods. RESULTS: The patient, a 49-year-old woman, presented with subacute onset headaches. An MRI T1W scan revealed a hemispheric mass with centrally reduced signal and ring enhancement. T2W images showed increased central signal with a rim of reduced signal co-localized to the enhancing ring. A biopsy was initially misinterpreted as demyelination alone, given abundance of histiocytes, the presence of hypertrophic astrocytes with micronuclei ("Creutzfeldt-Peters cells"), and occasional mitoses. Upon consultative review, two histologically distinct components, one inflammatory demyelination and the other an anaplastic astrocytoma were revealed. Subsequent complete resection of the abnormality demonstrated a WHO grade IV astrocytoma (glioblastoma multiforme). CONCLUSION: Our experience underscores the importance of adequate tissue sampling during biopsy for suspected glioma, and confirms the fact that active inflammatory demyelination may coexist with a high-grade glioma. Despite detailed study, the basis for the association remains elusive.

Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica.

BACKGROUND: Autoantibody specific for the aquaporin-4 astrocytic water channel is restricted to serum and CSF of patients with neuromyelitis optica (NMO) and related CNS inflammatory demyelinating disorders (relapsing optic neuritis and longitudinally extensive transverse myelitis). NMO-typical lesions are distinct from MS-typical lesions. Aquaporin-4 is lost selectively at vasculocentric sites of edema/inflammation coinciding with focal deposits of immunoglobulins (Ig) G, M, and terminal complement products, with and without myelin loss. Evidence for antigen-specific autoantibody pathogenicity is lacking. METHODS: We used confocal microscopy and flow cytometry to evaluate the selectivity and immunopathological consequences of Ig binding to surface epitopes of living target cells expressing aquaporin-4 fused at its cytoplasmic N-terminus with GFP. We tested serum, IgG-enriched and IgG-depleted serum fractions, and CSF from patients with NMO, neurologic control patients, and healthy subjects. We also analyzed aquaporin-4 immunoreactivity in myelinated adult mouse optic nerves and spinal cord, and plasma cell Ig isotypes in archived brain tissue from an NMO patient. RESULTS: Serum IgG from patients with NMO binds to the extracellular domain of aquaporin-4; it is predominantly IgG(1), and it initiates two potentially competing outcomes, aquaporin-4 endocytosis/degradation and complement activation. Serum and CSF lack aquaporin-4-specific IgM, and plasma cells in CNS lesions of NMO contain only IgG. Paranodal astrocytic endfeet highly express aquaporin-4. CONCLUSIONS: NMO patients' serum IgG has a selective pathologic effect on cell membranes expressing aquaporin-4. IgG targeting astrocytic processes around nodes of Ranvier could initiate demyelination.

A population-based study of familial hemiplegic migraine suggests revised diagnostic criteria.

Familial hemiplegic migraine (FHM) is a rare autosomal dominantly inherited subtype of migraine with aura. The clinical characteristics of FHM have been described previously in selected materials or case studies, but population-based studies are important in order to analyse the full spectrum of the disorder. The aim of the present study was to perform a systematic search for familial cases of migraine with an aura that included motor weakness in order to generate non-selected material of as many FHM cases as possible in the Danish population of 5.2 million inhabitants, and to compare this material with already available population-based clinical descriptions of migraine with typical aura (MA). Due to the rarity of FHM, traditional population-based methods were not feasible. Therefore, the search strategy employed a computer search of the National Patient Register, screening >27 000 case records from headache clinics and private neurologists, and advertisements. A total of 147 affected FHM patients from 44 families were identified. FHM patients most often had all four 'typical' aura symptoms (visual, sensory, aphasic and motor symptoms) and all had at least two of these aura symptoms during FHM attacks. The motor, sensory and visual aura symptoms were all similar in type to the motor, sensory and visual aura symptoms in MA, but FHM had a statistically significantly longer duration of the visual and sensory aura symptoms, and these and other aura symptoms often fulfilled the criteria of the International Headache Society for prolonged aura. In addition, 69% had basilar migraine (BM) symptoms during FHM attacks. The order of the aura symptoms was usually visual, followed by sensory, aphasic, motor and, lastly, basilar-type migraine symptoms. Headache was present in 99% of FHM patients during FHM attacks, whereas the aura symptoms more often occurred without headache in MA. Headache duration was significantly longer in FHM compared with MA. Based on these data, we suggest more precise diagnostic criteria for FHM and a more clear clinical distinction between FHM and BM. Our results have significant implications for case finding in genetic studies and for clinical migraine differential diagnosis.