One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease 1,2 . This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS) 1-4 . There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/ tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5 -7 ). HAM/TSP patients develop antibodies to neurons 8 . We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5 ,9 ). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged 7 . Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS. To test for molecular mimicry between an environmental agent and the central nervous system (CNS), we isolated immunoglobulin G (IgG) from the serum of patients with human Tlymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and tested it for reactivity with human tissues (Fig. 1a). There was intense staining of neurons in brain and no staining of glia, dorsal root ganglion (peripheral nervous system) or systemic organs. A monoclonal antibody to HTLV-1-tax (tax mAb) mimicked IgG staining of neurons. To identify the protein, cortical neurons were isolated, proteins extracted and subjected to SDS-PAGE and western-blot analysis. The IgG recognized a band of approximately 33 kD (Fig. 1b), whereas IgG isolated from controls did not. Importantly, the tax mAb that stained CNS neurons reacted with the antigen. All patients with HAM/TSP (13/13) developed antibodies recognizing the neuronal antigen 8 . Nine of ten HTLV-1-seropositive patients without neurological symptoms and 12 HTLV-1-seronegative controls showed no reactivity (P < 0.0001 versus HAM/TSP) 8 . Clinically, the HAM/TSP patients presented with progressive neurological disease in which corticospinal tract damage (weakness, spasticity and pathological reflexes) predominated 6 . Many of our patients were originally diagnosed with MS. In fact, one of our patients was diagnosed with MS for 20 years before HTLV-1 testing 10 .To establish a direct link between the immune response to HTLV-1 and the neurological...

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Summary: Purpose:To evaluate the determinants of postoperative change in visual confrontation naming ability and the differential sensitivity of two common tests of confrontation naming.Methods: In a group of 99 patients undergoing lobectomy of the left, language-dominant anterior temporal lobe, we examined naming ability using two measures: the 60 item Boston Naming Test (BNT), and the Visual Naming (VN) subtest of the Multilingual Aphasia Examination (MAE). ATL entailed resection of lateral temporal lobe followed by microsurgical complete removal of hippocampus. Language mapping was not performed. The status of the resected hippocampus was graded on a scale 0-4 of hippocampal sclerosis (HS). A dichotomous grouping HS-(grades 0 and 1, n = 34) and HS+ (grades 3 and 4, n = 61) was effected. Age at surgery, age of epilepsy onset, sex, extent of lateral temporal resection, Full-Scale IQ (FSIQ), and preoperative naming scores were also examined as potential predictors of pre-versus postoperative naming change.Results: Preoperative BNT and VN scores were significantly worse for HS+ than for HS-(BNT, p c 0.05; VN, p = 0.001).Postoperatively, BNT and VN scores significantly declined for HS-as compared with HS+ patients (p c 0.001). For individual risk, the 90th centile of reliable change index (RCI) was used. By this criterion, of the total sample, 39% evidenced decline on the BNT and 17% evidenced decline on the VN. Logistic regression analysis with backward elimination showed HS to be the only predictor of decline in BNT and HS and sex to be the only predictors of VN decline. Males were more at risk than females. Age, age at onset, extent of lateral resection, preoperative scores, and FSIQ were not predictors. Using age at onset as a proxy for HS+/HS-we calculated probabilities for naming decline for given onset age. Conclusions: Both preoperative and postoperative change in naming ability are associated with the pathological status of the hippocampus. The potential interpretations and implications of these findings are discussed.

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The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression-based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed.

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This investigation tested the hypothesis that the degree of impairment to memory function caused by an anterior temporal lobectomy (ATL) is inversely related to the pathological status of the resected hippocampus. Specifically, the greatest risk to postoperative memory function should be to patients with no or minimal hippocampal sclerosis, i.e., those with a functional hippocampus. Forty patients who underwent a partial resection of the left (n = 21) or right (n = 19) anterior temporal lobe were administered tests of immediate and delayed verbal and figural memory, both preoperatively and 6 months postoperatively. The degree of postoperative impairment in memory function was then investigated as a function of the degree of hippocampal sclerosis, as determined by a standardized procedure. For a left ATL, an absence or mild degree of hippocampal sclerosis was associated with significantly greater postoperative impairment of both verbal and figural memory, compared with patients with moderate or marked sclerosis. No statistically significant relationship was noted for patients who underwent a right ATL, but the findings were in the same direction for five of six memory measures. It may be possible to predict and avoid surgically induced impairment of memory function among patients who undergo left ATL through the use of preoperative hippocampal volumetric magnetic resonance imaging. Better clinical tests of right hippocampal function are needed to predict the outcome for patients who undergo a right ATL.

This study hypothesized that verbal memory decline following anterior temporal lobectomy (ATL) is associated with a lack of significant neuropathology in resected left, but not right, hippocampus and is limited to measures of episodic memory only. Tests of immediate (digit span), semantic (visual naming), and episodic memory as measured by the California Verbal Learning Test (CVLT) were administered before and 6 months after resection of the anterior left (n = 36) or right (n = 26) temporal lobe. There were no effects of hippocampal pathology on measures of immediate or semantic memory for either ATL group or for episodic memory for the right ATL group. Left ATL patients who demonstrated no/mild hippocampal sclerosis exhibited significantly greater postoperative decline in episodic memory compared with those with moderate/marked hippocampal sclerosis on multiple CVLT indices (recall measures, learning characteristics, and contrast measures).