Clinical features and anti-neural reactivity in neuropathy associated with IgG monoclonal gammopathy of undetermined significance.

Neuropathy has been frequently reported in patients with IgG monoclonal gammopathy of undetermined significance (MGUS) but it is still unclear whether this association has clinical or pathogenetic relevance. In order to clarify the possible role of IgG MGUS in the neuropathy we correlated the clinical and electrophysiological features of the neuropathy with the duration and anti-neural activity of the M-protein in 17 patients with neuropathy and IgG MGUS. Ten patients (59%) had a chronic demyelinating neuropathy clinically indistinguishable from chronic inflammatory demyelinating polyneuropathy (CIDP) while 7 (41%) had a predominantly sensory axonal or mixed neuropathy. In 80% of patients in the CIDP-like and 28% in the sensory group the IgG M-protein became manifest several months to years after onset of the neuropathy. Antibodies to one or more neural antigens (including tubulin, a 35KD P0-like nerve myelin glycoprotein, GD1a, GM1 and chondrotin sulfate C) were found in 40% of patients with CIDP-like and 43% with sensory neuropathy but also in 37% patients with IgG MGUS without neuropathy. Neuropathy associated with IgG MGUS is probably less heterogeneous than previously considered suggesting that this association may not be merely casual. The evidence for primary pathogenetic role of IgG M-proteins in the neuropathy remains however elusive.

Solitary neurinoma of the anterior cranial fossa. Case report.

A case of solitary neurinoma of the anterior cranial fossa, protruding into the ethmoidal region and into the right orbita, in a 44-year old woman is reported. The four cases previously described are reviewed and the possible origin of these tumors is discussed.

Multiple diverse intracranial and intramedullary spinal tumors. Report of a case.

A case of spinal ependymoma diagnosed 26 years after the removal of an acoustic neurinoma in a patient free of von Recklinghausen's disease is described. The extreme rarity of such a finding and the pathogenetic hypotheses regarding multiple primary tumors of the nervous system are discussed at the light of the literature.

Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a multicenter study.

OBJECTIVES: Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria. METHODS: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. RESULTS: A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up. CONCLUSIONS: Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds.

Stroke and transient ischaemic attack in 18 neurology departments from two Italian Regions: the SINPAC database.

This observational prospective multicentre study aims to describe a hospital-based database collecting information about clinical features, management and follow-up of stroke patients. In 18 neurological departments (mostly first-referral) in Piedmont and the Aosta Valley, Italy, between May and July 1999, 604 consecutive patients (97 TIA, 443 ischaemic, and 64 haemorrhagic stroke) were studied. Ischaemic stroke aetiologies were as follows: large-artery atherosclerosis (148), small-artery occlusion (133), cardioembolism (76), other causes (13) and undetermined (73). According to Bamford's classification, 164 were PACI, 126 LACI, 87 TACI and 66 POCI. The diagnostic workup and management of patients is described; only 4% of patients did not receive a CT scan. Four hundred and three patients were discharged to their home, 78 to a rehabilitation unit, 44 to long-term institutional care, 20 to other wards and 59 died while in hospital. After six months, 10 patients were lost to follow-up, 499 were alive and 95 had died. The SINPAC database allows for evaluation of current practice of care in a first-referral stroke population.

Cerebral venous thrombosis: a retrospective multicentre study of 48 patients.

The objective was to describe the clinical features and management of cerebral venous thrombosis (CVT) in non-selected centres. An observational study in 11 neurological departments in NW Italy was carried out from 1995 through 1999 on 38 female and 10 male patients. Mean age: 44.8 years, SD=14.3. Onset: acute in 21 patients (44%), subacute in 17 (35%) and chronic in 10 (21%). Most frequent onset: with focal deficits and/or seizures, followed by impaired consciousness or confusion, isolated headache, isolated intracranial hypertension and cavernous syndrome. No risk factor was found in 8 patients (17%). The superior sagittal sinus was involved in 27 patients (56%) and the transverse sinus in 29 (60%). Anticoagulants were used in 45 patients (94%). Rankin Scale score at discharge: 0 (27 patients), 1 (four), 2 (five), 3 (five), 4 (none), 5 (one) and six were dead. Thirteen patients had deep CVT: age, risk factors, neurological signs and outcome differed from cortical CVT (35 patients), although not significantly. Clinical features, risk factors and outcome of CVT patients from non-selected centres are similar to those from specialised centres.

Histological observations on the regrowth of malignant gliomas after radiotherapy and chemotherapy.

The reproliferation of glioblastomas after radiation and chemotherapy has been studied in 25 tumors by means of whole mount histological preparations. The tumors have been subdivided into four groups according to the radiation dose and the distance from the end of radiation. After 4,000 rad vessel proliferations and mitoses stop, while vessel degenerations and astrocytes with deformed nuclei appear. Six months after 6,000 rad have been delivered, repopulation phenomena are clearly evident and are mainly represented by mitoses both in parenchyma and in the vessel walls, circumscribed necroses with pseudopalisadings, proliferations of formerly degenerated vessels, etc. The brain adjacent to tumor (BAT) has a great importance since it is one of the reproliferating sites, even though it may be unrecognizable for the occurrence of radiation damages.

Effects of radiotherapy on the astrocytomatous areas of malignant gliomas.

Little is known of the histological effects of radiation on low grade astrocytomas, whereas the clinical efficacy of radiotherapy on these tumors is still a matter of discussion. Since it is difficult to have large series of autoptic brains harboring astrocytomas, the wide astrocytomatous areas of conventionally irradiated secondary glioblastomas have been studied in whole mount preparations. It was assumed that these areas were already present at the time of irradiation. In these areas no histologic changes referable to 'short-term' effect of radiation have been found. When the astrocytomatous areas were located in the white matter, they were affected by chronic edema, which usually occurs in periglioblastomatous tissue. In one case necrotic foci in the astrocytomatous areas were interpreted as anaplastic foci damaged by radiation; radiotherapy of astrocytomas might therefore result in the eradication of undetected anaplastic foci.

Delayed adverse effects after irradiation of gliomas: clinicopathological analysis.

Out of 107 pts. treated with radio- and chemotherapy for low and high grade gliomas (TD: 45-65Gy), 3 cases developed pathologically documented radionecrosis (coagulative necrosis with minimal or no persistent tumor). Clinico-therapeutic modalities were analyzed for all cases and biologically equivalent doses were calculated according to NSD, ED and btu formulas. All cases of radionecrosis fell into the group of doses close to 60Gy/30fx./42d. and NSD = 1758, ED = 1340 and btu = 1161. Isodose curve reconstruction on planes corresponding to histological sections of brains with radionecrosis demonstrated that doses received by areas of necrosis were higher than the calculated mid-plane doses in two cases. Clinical and autoptic incidence of radionecrosis were 2.8% and 10% respectively. High doses of steroids during RT seemed to offer some protection against radionecrosis, while number of chemotherapy cycles did not influence the risk of radionecrosis. A higher autoptic rate of irradiated gliomas is needed in order to obtain a better understanding of a number of unresolved problems.

Autoantibodies to amphiphysin I and amphiphysin II in a patient with sensory-motor neuropathy.

A proportion of patients with peripheral neuropathies has circulating autoantibodies directed against neural antigens. In some cases, autoantibodies may play a pathogenic role. We studied a patient with a progressive sensory-motor axonal neuropathy of unknown etiology, looking for circulating autoantibodies against neural antigens and we showed that the patient's serum contained anti-amphiphysin I (AMP I) and amphiphysin II (AMP II) autoantibodies. A sural nerve biopsy revealed an axonal neuropathy. Indirect immunofluorescence experiments with the patient's serum showed a staining of rat axons due to alpha-AMP I autoantibodies and a specific labelling of cytoplasm and Schmidt-Lanterman incisures of Schwann cells due to alpha-AMP II autoantibodies. In conclusion we identified a patient affected by a sensory-motor neuropathy with autoantibodies against both AMP I and AMP II.