Very early semantic dementia with progressive temporal lobe atrophy: an 8-year longitudinal study.

BACKGROUND: Semantic dementia is a syndrome within the spectrum of frontotemporal lobar degenerations characterized by fluent progressive aphasia (particularly anomia) and loss of word meaning. OBJECTIVE: To report a unique case of very early semantic dementia with a slowly progressive course, allowing insights into the early natural history of this disorder. DESIGN: Case report. SETTING: A tertiary care center. PATIENT: A 62-year-old woman who presented with "memory loss" complaints. MAIN OUTCOME MEASURES: Clinical course, neuropsychological data, and magnetic resonance imaging results. RESULTS: The patient was first evaluated when the results of standard neuropsychological measures were normal but subtle left anterior temporal lobe atrophy was present. During the follow-up period of 8 years, she developed profound anomia and loss of word meaning associated with progressive left anterior temporal lobe atrophy, consistent with semantic dementia. In more recent years, anterograde memory impairment and mild prosopagnosia evolved in association with left hippocampal atrophy and subtle atrophy in the homologous gyri of the right anterior temporal lobe. She remains functionally independent despite her current deficits. CONCLUSIONS: Early identification of patients who will develop semantic dementia is difficult and might be missed with standard clinical, neuropsychological, and structural neuroimaging evaluations. Recognition of this relatively rare syndrome is important for early diagnosis and prognostication and particularly for therapeutic interventions in the future.

Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.

Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy ("CAR"-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). Among 16 patients with CRMP-5-IgG and optic neuritis (aged 52-74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR-IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4(+) (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7-32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP-5-IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8(+) T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small-cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity. In summary, CRMP-5-IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer.