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We describe a 30-year-old woman with an infantile-onset epilepsy due to a left temporal gliotic area who developed a nonconvulsive status epilepticus (NCSE) during tiagabine (TGB) adjunctive therapy. The ictal EEG recording showed a de novo right temporal focus not previously evident. After the i.v. administration of 4 mg lorazepam, the NCSE episode rapidly resolved and her usual left temporal EEG abnormalities reappeared. To our knowledge this is the first case of paradoxical seizure exacerbation associated with TGB therapy in which the clinical and EEG features are congruous with a new contralateral focus.

To investigate the role of plasma lipid abnormalities in ischemic cerebrovascular disease related to primary vessel disease, the authors assess lipid profiles in a hospital-based cohort of 202 consecutive patients with atherothrombotic or lacunar stroke subtypes. Lipoprotein (a) was the unique lipid parameter that differs between these two subtypes being its value twofold higher in patients with atherothrombotic than in lacunar stroke. This suggests that lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis.

We studied the records of 175 consecutive patients referred to our neurologic ward between January 1994 and February 2000 with a diagnosis of ischaemic cerebrovascular disease (ICVD) (stroke or transient ischaemic attack - TIA) who underwent transoesophageal echocardiography (TEE). We excluded patients with large vessel disease, high-risk embolic cardiopathies and other rare causes of stroke. According to clinical and neuroimaging findings, patients were divided into two groups. The lacunar (LAC) group (69/175 (39.4%)) and the nonlacunar (N-LAC) one (106/175 (60.6%)). The control population consisted of 78 consecutive patients, referred to the echocardiography laboratory for TEE without history of ICVD and known heart disorders. Patent foramen ovale (PFO) frequency was significantly higher in case patients than in control subjects (55/175 (31.4%) vs. 13/78 (16.6%); p = 0.02). Among case patients, PFO was more prevalent in the N-LAC group than in the LAC one (43/106 (40.6%) vs. 12/69 (17.4%); p = 0.0005). A large degree of shunt occurred in 53.5% of N-LAC patients and in 16.7% of LAC ones (p = 0.04). Atrial septal aneurysm (ASA) was detected in 12% of case patients and 1.3% of control subjects (p = 0.003) and was more frequent in the N-LAC group than in the LAC one (16 vs. 5.8%; p = 0.05). Mitral prolapse (MP) was present in 6/175 (3.4%) ICVD patients (vs. 1/78 among controls) in most cases associated with myxomatous valve redundancy. Aortic arch atheromas (AA) were detected in 12% of ICVD patients and in 10.2% of controls. The frequency was 9.4% in N-LAC and 15.9 in LAC. No complicated AA (plaque thickness >4 mm, ulcerated atheroma, superimposed thrombus) were detected. After multivariate analysis, PFO (OR = 3.8; 95% CI = 2.7-7.9) and ASA (OR = 8.01; 95% CI = 3.0-16.1) appeared to be independent predictors of ICVD. PFO (OR = 2.24; 95% CI = 1.24-4.92) was also independently associated with N-LAC stroke subtype and its importance was even higher in younger patients. Our study provides further evidence that TEE is a helpful diagnostic tool in stroke patients without arterial and major cardiac sources of embolism. However, its utility differs according to type and localization of the ischaemic lesion being more relevant in patient with N-LAC infarctions., (Copyright 2002 S. Karger AG, Basel)

Background: Isolated office (IO) hypertension is a benign condition according to some researchers, whereas others believe it is associated with cardiovascular abnormalities and increased cardiovascular risk. The aim of this study is to compare morphofunctional characteristics of the left ventricle (LV) in IO hypertensive subjects, normotensive subjects (hereafter, hypertensives and normotensives), and never-treated sustained hypertensives. The 3 groups were matched not only by age, sex, and body mass index but also by clinic blood pressure (BP) (IO hypertensives and sustained hypertensives) and daytime BP (IO hypertensives and normotensives)., Methods: We enrolled 42 IO hypertensives (clinic BP > 140 and/or 90 mm Hg and daytime BP < or = 130/80 mm Hg), 42 sustained hypertensives (clinic BP > 140 and/or 90 mm Hg and daytime BP > or = 140 and/or 90 mm Hg) and 42 normotensives (clinic BP < 135 and/or 85 mm Hg and daytime BP < or = 130/80 mm Hg). Left ventricular morphologic features and function were assessed using digitized M-mode echocardiography., Results: Compared with normotensives, IO hypertensives had significantly thicker LV walls, increased LV mass, reduced diastolic function, increased prevalence of LV hypertrophy, and preclinical diastolic dysfunction. Sustained hypertensives, compared with IO hypertensives, had significantly thicker LV wall, higher LV mass, and lower diastolic function, whereas the prevalence of LV hypertrophy and preclinical diastolic dysfunction was greater than in IO hypertensives, but the difference did not reach statistical significance (P = .29)., Conclusions: Comparing matched BP groups, IO hypertensives have LV morphofunctional characteristics considerably different from normotensives and qualitatively similar to sustained hypertensives. Therefore, our results support the hypothesis that IO hypertension should not be considered as simply a benign condition.

Using 24-h ambulatory blood pressure (BP) monitoring and digitized M-mode echocardiography, we evaluated whether microalbuminuria is related to preclinical left ventricular (LV) diastolic dysfunction in hypertensive patients. We selected 87 never-treated hypertensive patients (mean 24-h BP > 140 and/or > 90 mm Hg); albuminuria was evaluated as mean value of 24-h urinary albumin excretion (UAE) from two 24-h urine collections. Microalbuminuria was found in 28 patients, classified as MA+ (UAE 30 to 300 mg/24 h); 59 patients had normal UAE (< 30 mg/24 h) and were classified as MA-. The MA+ and MA- groups did not differ with regard to age, sex, body mass index, or 24-h heart rate, whereas 24-h, daytime, and nighttime systolic and diastolic BP were significantly higher in MA+ than in MA-. The LV mass index was greater in MA+, as was the prevalence of LV hypertrophy; peak shortening rate of LV diameter, index of systolic function, was normal in all, but was lower in MA+. Peak lengthening rate of LV diameter and peak thinning rate of posterior wall, indices of diastolic function, were lower in MA+ and the prevalence of diastolic dysfunction was higher in MA+. UAE was inversely correlated with both indices of LV diastolic function, also after correction for age, 24-h heart rate, 24-h BP, and LV mass. In conclusion, in never-treated hypertensive patients, microalbuminuria is not only associated with greater myocardial mass, but is also related with preclinical impairment of LV diastolic function. This relation, independent from increased BP or LV mass, strengthens the role of microalbuminuria as an early and reliable marker of preclinical cardiac involvement.

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epileptic syndrome distinctively characterized by myoclonic jerks often associated to generalized tonic-clonic seizures (GTCS) and typical absence seizures. In spite of typical clinical and EEG profiles, JME is widely underdiagnosed. In the present study we retrospectively revised clinical and EEG data of JME patients referring to our Epilepsy Service. A diagnosis of JME could be made in 63 patients, that is 5.7% of all the epileptic patients referring to our Service and 25.9% of those suffering from an idiopathic generalized epilepsy. General features as well as modality of onset and course of the syndrome of our JME subjects were in accordance with literature. Regarding EEG findings, asymmetries were detected in 38.1% of cases. At referral to our Service only 31.7% of JME patients were correctly diagnosed. Main factors responsible for misdiagnosis were failure in eliciting a history of myoclonic jerks and misinterpretation of myoclonic jerks as simple partial seizures. EEG asymmetries were misleading in 13 patients. In conclusion, a correct JME diagnosis is strictly dependent on the knowledge of the syndrome leading the interviewer to look for and correctly interpret myoclonic jerks whereas EEG is just an ancillary diagnostic tool.

Background: Various sensory syndromes in lateral medullary infarctions are described. A small variation in the location of a lesion may lead to very different clinical features, owing to the complex anatomy of the medulla oblongata. MRI may identify the location and extent of the ischemic lesions, allowing a clear clinical-anatomical correlation., Case Description: We describe a man with an ischemic lesion in the right portion of the lower medulla that presented a contralateral impairment of spinothalamic sensory modalities and an ipsilateral impairment of lemniscal modalities with a restricted distribution (left forearm and hand, right hand and fingers, respectively). The restricted and dissociated sensory abnormalities represent the only permanent neurological consequence of that lesion., Conclusions: The atypical sensory syndrome may be explained by the involvement of the medial portion of spinothalamic tract and the lateral portion of archiform fibers at the level of the lemniscal decussation.

We show that normal peripheral nerve myelination depends on strict dosage of the most abundantly expressed myelin gene, myelin protein zero (Mpz). Transgenic mice containing extra copies of Mpz manifested a dose-dependent, dysmyelinating neuropathy, ranging from transient perinatal hypomyelination to arrested myelination and impaired sorting of axons by Schwann cells. Myelination was restored by breeding the transgene into the Mpz-null background, demonstrating that dysmyelination does not result from a structural alteration or Schwann cell-extrinsic effect of the transgenic P(0) glycoprotein. Mpz mRNA overexpression ranged from 30-700%, whereas an increased level of P(0) protein was detected only in nerves of low copy-number animals. Breeding experiments placed the threshold for dysmyelination between 30 and 80% Mpz overexpression. These data reveal new points in nerve development at which Schwann cells are susceptible to increased gene dosage, and suggest a novel basis for hereditary neuropathy.

Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy reduces exacerbation rate and MRI signs of disease activity in relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the possible mechanisms underlying the clinical efficacy of rIFNA in MS, several immunologic studies were performed as a part of a pilot clinical trial. Twenty RR MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Cytokine production by cultured lymphocytes, major histocompatibility complex class II (MHC-II) antigen expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied before therapy, after 6 months of therapy, and 6 months after stopping therapy. rIFNA therapy was associated with reduction of interferon-gamma and tumor necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight, not significant, increase of transforming growth factor-beta 2 or interleukin (IL)-10 production. IL-4 was undetectable in the culture supernatants both before and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+ CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA therapy. After rIFNA administration, IgG level significantly increased both systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients developed neutralizing antibodies against rIFNA during therapy. Six months after stopping therapy all the immunologic changes returned to baseline. These data suggest that the beneficial effect of rIFNA therapy on MS disease activity is probably mediated by a downregulation of proinflammatory cytokine synthesis by PB lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic effects of high-dose systemic rIFNA therapy are temporary and restricted to the period of drug administration.

We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.