A novel antineuronal antibody in a motor neuron syndrome associated with breast cancer.

A 72-year-old woman developed a lower motor neuron syndrome (MNS) 4 months before the appearance of breast cancer. Monoparesis progressed to quadriparesis despite high-dose IV immunoglobulins, plasma exchange, and azathioprine, and high-dose IV methylprednisolone. The patient improved only after the removal of the tumor. MRI demonstrated hyperintensities in the cervical spinal cord. The patient had antibodies that reacted with axonal initial segments and nodes of Ranvier. The findings suggest that in this patient lower MNS may be a paraneoplastic condition associated with breast cancer.

Marchiafava-Bignami disease: computed tomographic scan, 99mTc HMPAO-SPECT, and FLAIR MRI findings in a patient with subcortical aphasia, alexia, bilateral agraphia, and left-handed deficit of constructional ability.

OBJECTIVES: To report and discuss the neuropsychological deficits and neuroimaging findings in a patient with probable Marchiafava-Bignami disease. DESIGN AND METHOD: A right-handed woman with chronic alcoholism demonstrated mutism, impaired comprehension of spoken language, alexia, and right-handed agraphia. The syndrome of interhemispheric disconnection was manifested by left-handed deficit of constructional ability and agraphia. The patient underwent brain computed tomographic scans, technetium 99 hexylmethylpropylene amineoxime-single photon emission computed tomography, and magnetic resonance imaging (MRI) that also included fluid attenuated inversion recovery images. SETTING: Clinical neurology department. RESULTS: The patient's symptoms were related to scattered lesions of the corpus callosum and to extensive symmetrical lesions of the centrum semiovale. Only the latter were detected by computed tomographic scans. Results of single photon emission computed tomography did not show areas of focal hypoperfusion. Results of fast spinecho MRI showed all lesions were hyperintense in T1-weighted images and hypointense in T2-weighted images. Fluid attenuated inversion recovery images revealed that periventricular lesions had a hypointense core surrounded by a hyperintense rim; callosal lesions were still hyperintense. CONCLUSIONS: We believe that our patient's symptoms are due to the discontinuous affection of the corpus callosum and to the bilateral cutting of the outflow from the cortex. The MRI findings may be interpreted as indicating central necrosis and peripheral demyelination of periventricular lesions and demyelination of the corpus callosum. The combined use of fast spin echo and fluid attenuated inversion recovery MRI reproduced with more accuracy than fast spin echo MRI alone some features of Marchiafava-Bignami disease known from observations at autopsy.

Transient global amnesia and transient ischemic attack: a community-based case-control study.

OBJECTIVES: Few case-control studies of first-ever transient global amnesia (TGA), transient ischemic attack (TIA) and normal controls have been performed to date. We aimed to assess the prevalence of cerebrovascular risk factors in a well defined population of TGA patients. MATERIAL AND METHODS: We undertook a retrospective and prospective community-based case-control study of 170 first-ever TGA, 170 first-ever TIA and 170 normal controls. RESULTS: Age-matched analysis revealed that TGA cases had a significantly lower prevalence of atrial fibrillation and diabetes mellitus than TIA controls. The prevalence of cigarette smoking and diabetes mellitus was significantly higher in normal controls than in TGA cases. CONCLUSION: Our community-based case-control study showed that atrial fibrillation and diabetes mellitus, two important risk factors for cerebrovascular disease, were significantly more common in the TIA group than in the TGA one. These results make the thromboembolic pathogenesis of TGA unlikely.

Recurrent external ophthalmoparesis during hormonal therapy after thyroid ablation. Case report.

We here report the case of a patient who had undergone total thyroid ablation for Graves' disease. After the beginning of oral therapy with 1-thyroxine, she developed a left external ophthalmoparesis that remitted with the discontinuation of the drug and recurred whenever the replacement therapy (1-thyroxine or tri-iodothyronine) was reintroduced.

Incidence of transient global amnesia in the Belluno province, Italy: 1985 through 1995. Results of a community-based study.

INTRODUCTION: We sought to determine the incidence rate of all the new cases of first-ever-in-a-lifetime transient global amnesia in the Belluno province, Italy. Only two prospective epidemiological studies on TGA incidence have been performed to date, non in Italy. Our study aimed to provide reliable and comparable information on TGA incidence. MATERIAL AND METHODS: We undertook a prospective population-based study in the territory of the province of Bulluno, Italy, between June 1, 1992 and December 31, 1995. We also retrospectively reviewed the clinical records of all the patients with a diagnosis of amnesia seen in the hospitals of the study area from January 1, 1985 through May 31, 1992. RESULTS: During the prospective study period we identified 77 patients who experienced a first-ever TGA. The crude annual incidence rate was 10.4/100,000 (9.35/100,000 for men and 11.37/100,000 for women). After adjustment to the European population, the incidence rate decreased to 8.60/100,000 per year. The crude annual incidence rate during the retrospective study period was 5.81/100,000. The demographic and clinical features of the two groups did not differ one to the other. CONCLUSIONS: The incidence rate of first-ever TGA registered in the province of Belluno, Italy, was closely similar to that reported in Turku, Finland and confirms that TGA is more common than has been usually proposed. We emphasize the usefulness of prospective, rather than retrospective, epidemiological studies for research on TGA.

Incidence of transient ischemic attacks in the Belluno Province, Italy. First-year results of a community-based study.

OBJECTIVES: This study formed part of a larger prospective population-based survey on cerebrovascular diseases and aimed to provide reliable and comparable results on TIA incidence and on related risk factors, which could supply investigation objectives and support information for primary and secondary prevention. MATERIAL AND METHODS: We undertook a prospective population-based study in the province of Belluno, an area located in the North-East of Italy where 211,389 people live, utilizing all the possible case-collection sources available in the territory. RESULTS: In the first year of the study (June 1, 1992 to May 31, 1993) 271 patients with a diagnosis of transient ischemic attack were recruited. Among these, we recorded 171 cases of new TIAs. The crude annual incidence rate for new TIAs was 0.80 per 1000, 0.73 per 1000 for men and 0.87 per 1000 for women. After adjustment to the European population, the overall incidence rate decreased to 0.58 per 1000 inhabitants per year. The mean age of new TIA patients was 73.91 years and females were significantly older than males (p < 0.001). A CT scan disclosed an infarct in 21 new TIA patients. CONCLUSION: Our first-year results on new TIAs incidence did not differ from the findings reported in previous population-based studies performed throughout the world and support data as to risk factors for TIA.

Incidence and prognosis of stroke in the Belluno province, Italy. First-year results of a community-based study.

BACKGROUND AND PURPOSE: We sought to register the incidence rate, risk factors, and case-fatality rate of all the new cases of first-ever-in-a-lifetime stroke in the province of Beluno, Italy. This study aimed to provide an epidemiological survey of cerebrovascular disease that could supply investigative objectives and support information for regional healthcare facilities planning. METHODS: We undertook a prospective population-based study in the territory of the 1st, 2nd, 3rd, and 4th local health units in the province of Belluno, an area located in northeast Italy (population, 211 389). RESULTS: In the first year of the study (June 1, 1992, to May 31, 1993), 474 cases of first-ever stroke were registered. The crude annual incidence rate was 2.24/1000 (2.01/1000 for men and 2.45/1000 for women). After adjustment to the European population, the incidence rate for first stroke was 1.70/1000 per year. The pathological diagnosis was confirmed by a CT scan in 89.5% of cases. Cerebral infarction accounted for 319 cases, while 93 patients suffered a primary intracerebral hemorrhage, 12 patients a subarachnoid hemorrhage, and 50 patients a stroke of unknown origin. The overall 30-day case-fatality rate was 33%, and the mortality within the first week from stroke onset was 23%. The recurrence rate after 1 month was 1.9%. After 1 month, 46% of our patients were functionally independent in activities of daily living. CONCLUSIONS: Our first-year results confirm the fairly high risk for stroke in central and northern Italy and support European findings regarding risk factors for stroke.

The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer.

Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by progressive rigidity of the body musculature with superimposed painful spasms. An autoimmune origin of the disease has been proposed. In a caseload of more than 100 SMS patients, 60% were found positive for autoantibodies directed against the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Few patients, all women affected by breast cancer, were negative for GAD autoantibodies but positive for autoantibodies directed against a 128-kD synaptic protein. We report here that this antigen is amphiphysin. GAD and amphiphysin are nonintrinsic membrane proteins that are concentrated in nerve terminals, where a pool of both proteins is associated with the cytoplasmic surface of synaptic vesicles. GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution. This finding suggests a possible link between autoimmunity directed against cytoplasmic proteins associated with synaptic vesicles and SMS.

Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer.

BACKGROUND: The stiff-man syndrome is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. Autoantibodies directed against glutamic acid decarboxylase are present in about 60 percent of patients with the syndrome. In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus. METHODS: We studied three women with the stiff-man syndrome and breast cancer, seeking autoantibodies directed against nervous system antigens in serum and cerebrospinal fluid by immunocytochemical techniques, Western blotting, and immunoprecipitation. RESULTS: Autoantibodies directed against a 128-kd brain protein were found in two of the women with the stiff-man syndrome and breast cancer. These results led to a search for breast cancer in the third patient with the stiff-man syndrome, who also had autoantibodies. A small invasive ductal carcinoma was detected by ultrasonography and removed. Serum samples from all three patients were negative for autoantibodies directed against glutamic acid decarboxylase. Autoantibodies against the 128-kd antigen were not detected in control patients with the stiff-man syndrome without breast cancer or in patients with cancer who did not have the syndrome. Within the nervous system, the 128-kd autoantigen was localized in neurons and concentrated at synapses. CONCLUSIONS: In a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.

[Value and limits of C.T. scan in neurologics diseases in infancy and childhood (author's transl)]. / Utilità e limiti della T.C. nelle malattie neurologiche in età pediatrica.

The results obtained in 151 children who underwent C.T. scan at the Pediatric Department of the University of Padova are reported. The high incidence of negative or aspecific results in the cases of static encephalopathy, in primary generalized epilepsy and in acute diffuse cerebral infectious process is emphasized. C.T. confirmed its high diagnostic value in tuberous sclerosis and cerebral abscess. While non providing the precise diagnosis it may be helpful in some demyelinating diseases. In secondary generalized epilepsy and in partial epilepsy C.T. scan may suggest the prognosis and a possible surgical approach. On the basis of these results and of other published reports a greater selectivity in the use of C.T. is strongly recommended.