Cortical laminar necrosis following myocardial infarction

The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components – either neurons, glia cells and blood vessels – and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms

Lacosamide during pregnancy and breastfeeding

Background The epilepsy treatment during pregnancy represents a balance between teratogenic hazard and seizure control. The aim of the study was to evaluate the safety and efficacy of lacosamide (LCS) during pregnancy and breastfeeding. Methods Patients referred to our Epilepsy Center for pregnancy planning who became pregnant while taking LCS were prospectively followed-up. Data on seizure frequency, side effects, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation and development of newborns were collected. Results Three cases of maternal exposure to LCS were reported. Treatment with LCS was continued throughout pregnancy and breastfeeding at a median daily dose of 400mg. Lacosamide was used as monotherapy in two patients and as add-on treatment in one woman. Seizure frequency did not change throughout pregnancy and two subjects remained seizure free. The median gestational age at delivery was 39 weeks. The median Apgar scores at 1 and 5min were 9 and 10, respectively; no major or minor congenital malformations were observed in the offspring. Normal developmental milestone were reached by all new-borns. Conclusions Worldwide pregnancy registries have provided consistent and increasing information about the efficacy and safety of the older antiepileptic drugs during gestation, while data are lacking for many of the newer generations. These cases could suggest a good level of efficacy and safety for LCS throughout pregnancy and breastfeeding and argue against teratogenic or toxic potentialities

Elevated Blood Pressure in the Acute Phase of Stroke and the Role of Angiotensin Receptor Blockers

Raised blood pressure (BP) is common after stroke but its causes, effects, and management still remain uncertain. We performed a systematic review of randomized controlled trials that investigated the effects of the angiotensin receptor blockers (ARBs) administered in the acute phase (≤72 hours) of stroke on death and dependency. Trials were identified from searching three electronic databases (Medline, Cochrane Library and Web of Science Database). Three trials involving 3728 patients were included. Significant difference in BP values between treatment and placebo was found in two studies. No effect of the treatment was seen on dependency, death and vascular events at one, three or six months; the cumulative mortality and the number of vascular events at 12 months differed significantly in favour of treatment in one small trial which stopped prematurely. Evidence raises doubts over the hypothesis of a specific effect of ARBs on short- and medium-term outcomes of stroke. It is not possible to rule out that different drugs might have different effects. Further trials are desirable to clarify whether current findings are generalizable or there are subgroups of patients or different approaches to BP management for which a treatment benefit can be obtained

SELECTIVE ASSOCIATIVE PHONAGNOSIA AFTER RIGHT ANTERIOR TEMPORAL STROKE

We report the case of a 48 year old men who developed a selective impairment in famous voice recognition after ischemic stroke in right subcortical structures (lenticular nucleus and head of the caudate) and right anterior temporal lobe. He underwent fibrinolytic treatment. During the following days he progressively recovered and was discharged without neurological focal sign. Patent foramen ovale was found. When he got back to his house he noticed that he was unable to recognize the voice of his favoured singers and needed to ask who was the singer to his relatives. Neuropsychological examination revealed a selective impairment in famous voice recognition in the absence of alteration of voice perception, face perception and famous face recognition. All other neuropsychological domains were spared. In particular language, memory and executive functions were intact. Neuroimaging carried out by means of PET and MRI revealed two small ischemic lesions in the right subcortical region, involving lenticular and caudate nuclei and in the right temporal pole. To our knowledge, this is the first case described in literature of a patient showing a selective associative phonagnosia after right anterior temporal stroke. The present case helps to clarify the brain circuits underlying famous voice recognition and adds evidence in favour of a right hemisphere involvement in processing knowledge of familiar voices. These findings are discussed in relation to current models of brain organization of person-specific and general semantic knowledge.

MxA mRNA quantification and disability progression in interferon beta-treated Multiple Sclerosis patients

Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFNβ binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFNβ therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFNβ bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFNβ therapy

Longitudinal study on low-dose aspirin versus placebo administration in silent brain infarcts: the silence study

Background. We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment. Methods. We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment. Results. Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-A [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence. Conclusions. These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis. EU Clinical trial is registered with EudraCT Number: 2005-000996-16; Sponsor Protocol Number: 694/30.06.04

the heritage of glatiramer acetate and its use in multiple sclerosis

Multiple sclerosis (MS) is a chronic and progressively debilitating disease of the central nervous system. Treatment of MS involves disease-modifying therapies (DMTs) to reduce the incidence of relapses and prevent disease progression. Glatiramer acetate (Copaxone®) was the first of the currently approved DMTs to be tested in human subjects, and it is still considered a standard choice for first-line treatment. The mechanism of action of glatiramer acetate appears to be relatively complex and has not been completely elucidated, but it is likely that it involves both immunomodulating and neuroprotective properties. The efficacy of glatiramer acetate 20 mg/mL once daily as first-line treatment in relapsing-remitting MS is well established, with ample evidence of efficacy from both placebo-controlled and active-comparator controlled clinical trials as well as real-world studies. There is also a considerable body of evidence indicating that the efficacy of glatiramer acetate is maintained in the long term. Clinical trial and real-world data have also consistently shown glatiramer acetate to be safe and well tolerated. Notably, glatiramer acetate has a good safety profile in women planning a pregnancy, and is not associated with foetal toxicity. Until recently, glatiramer acetate was only approved as 20 mg/mL once daily, but a new formulation with less frequent administration, 40 mg/mL three times weekly, has been developed and is now approved in many countries, including Italy. This review examines the mechanism of action, clinical efficacy, safety and tolerability of glatiramer acetate to provide suggestions for optimizing the use of this drug in the current MS therapeutic scenario