Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: a proof-of-concept, observational study.

PURPOSE: To evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients. METHODS: We enrolled 16 patients (7 M/9 F; 77 ± 7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400 mg over 30 min, followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24 h following treatment, as evaluated by EEG recording and clinical observation. RESULTS: LCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45-60 min after administration. None of these patients relapsed in the following 24 h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six. CONCLUSIONS: This pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data.

Ictal epileptic headache mimicking status migrainosus: EEG and DWI-MRI findings.

We report a case of a patient with status migrainosus unresponsive to analgesic therapy in whom electroencephalographic recording revealed an epileptic origin. Intravenous administration of lorazepam induced the prompt resolution of the symptoms.

Levetiracetam in brain ischemia: clinical implications in neuroprotection and prevention of post-stroke epilepsy.

Several new antiepileptic drugs (AEDs) have been introduced for clinical use recently. These new AEDs, like the classic AEDs, target multiple cellular sites both pre- and postsynaptically. The use of AEDs as a possible neuroprotective strategy in brain ischemia is receiving increasing attention and the antiepileptic drug levetiracetam, a 2S-(2-oxo-1-pyrrolidiny1) butanamide, belonging to the pyrrolidone family, could have a crucial role in regulation of epileptogenesis and neuroprotection. Recent observations suggest that levetiracetam is both safe and effective against post-stroke seizures. In this review, the potential neuroprotective role in brain ischemia and the therapeutic implications of levetiracetam in post-stroke epilepsy are discussed.

Levetiracetam in newly diagnosed late-onset post-stroke seizures: a prospective observational study.

Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F, 71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures occurring at least 2 weeks after an ischemic stroke) in a prospective open-label study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%) at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke seizures.

Cerebrospinal fluid biomarkers in Parkinson's disease with dementia and dementia with Lewy bodies.

BACKGROUND: Clinical criteria for differentiating Parkinson's disease (PD) with dementia (PDD) from dementia with Lewy bodies (DLB) are unsatisfactory. Their existence as distinct clinicopathologic entities is still debated, although the burden of Alzheimer's disease (AD) pathology seems higher in DLB. Thus, analysis of cerebrospinal fluid (CSF) biomarkers (beta-amyloid(1-42) [Abeta42], total tau, and hyperphosphorylated tau [p-tau]) in living subjects might provide significant pathophysiological information on these diseases. METHODS: Cerebrospinal fluid biomarkers were measured in DLB (n = 19), PDD (n = 18), and AD (n = 23) subjects matched for age, sex, and dementia severity, as well as in PD (n = 20) and normal control subjects (n = 20). RESULTS: DLB showed the lowest mean CSF Abeta42 levels, with a negative association to dementia duration (rho = -.42, p = .07). In DLB patients, mean CSF total tau levels were significantly lower than in AD patients (508 +/- 387 vs. 960 +/- 619, respectively) but twofold to threefold higher than in PDD (286 +/- 184), PD (160 +/- 64), or normal control subjects (177 +/- 76), with a positive association to dementia severity (Mini-Mental State Examination: rho = -.54, p = .02; Milan Overall Dementia Assessment: rho = -.66, p = .002). PDD patients had mean CSF Abeta42 and total tau levels similar to those seen in PD patients. Hyperphosphorylated tau was significantly increased in the AD group only. CONCLUSIONS: Cerebrospinal fluid Abeta42 and total tau have a different behavior in DLB and PDD, being related to duration and severity of dementia in DLB alone. Hyperphosphorylated tau is not significantly altered in these conditions.

Lysosomal hydrolases in cerebrospinal fluid from subjects with Parkinson's disease.

Recent studies have shown a genetic association between glucocerebrosidase deficiencies and Parkinson's disease (PD). To further explore this issue the activity of beta-glucocerebrosidase and the activities of other lysosomal enzymes, alpha-mannosidase, beta-mannosidase, beta-hexosaminidase, and beta-galactosidase have been evaluated in the cerebrospinal fluid (CSF) of PD patients. The activities of alpha-mannosidase, beta-mannosidase, beta-glucocerebrosidase, and beta-hexosaminidase were substantially decreased in the CSF of PD patients, while levels of beta-galactosidase were essentially identical to controls. This study indicates that in PD several lysosomal hydrolases have decreased activities, further supporting a possible link between pathophysiological mechanisms underlying PD and lysosomal hydrolases.

Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally.

OBJECTIVE: The aim of the present research was to verify the levels of the soluble adhesion molecules sL- and sE-selectins, intercellular adhesion molecule (sICAM)-1, and vascular cell adhesion molecule-1 in serial samples of internal jugular venous blood taken from migraine patients without aura (MWoA) during attacks. The expression of leukocyte function antigen (LFA)-1 and very late activation antigen (VLA)-4 was also assessed on lymphocytes obtained from jugular venous blood. Levels of certain proinflammatory cytokines (tumor necrosis factor-alpha[TNF-alpha], interleukin-1beta[IL-1beta], IL-4, and IL-6) were also determined and correlated with those of adhesion molecules. PATIENTS AND METHODS: Seven MWoA patients were admitted in the hospital during attacks and blood samples were taken immediately after catheter insertion, at 1, 2, and 4 hours after attack onset, and within 2 hours after its termination. The levels of adhesion molecules and cytokines were measured with ELISA method. The expression of LFA-1 and VLA-4 was assessed by flow cytometry. RESULTS: A parallel transient increase of sICAM-1, TNF-alpha, and IL-6 was observed in the first 2 hours after attack onset compared with the time of catheter insertion (P < .0001, <.001, and <.003, respectively). The proportion of CD4+ and CD8+ T-cells expressing high levels of LFA-1 showed instead a progressive down-regulation with significantly lower percentages at 2 and 4 hours after attack onset (P < .01 and <.022, respectively). No variation in the percentage of VLA-4 expressing cells was observed at any time of the study. CONCLUSIONS: The transient increase in sICAM-1 and TNF-alpha found in the internal jugular blood of MWoA patients assessed ictally can be induced by sensory neuropeptides released from activated trigeminal endings. The progressive decrease in sICAM-1 levels during attacks and the down-regulation of LFA-1 expression by lymphocytes could antagonize their transvascular migration, supporting the hypothesis of sterile inflammation in the dura mater during migraine attacks.

Chemokine levels in the jugular venous blood of migraine without aura patients during attacks.

OBJECTIVE: To investigate changes in the levels of calcitonin gene-related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine patients without aura assessed during attacks, and to assess their relationship with the levels of IL-8, MCP-1, and RANTES in the same samples. BACKGROUND: Calcitonin gene-related peptide, the marker of trigeminovascular activation, is released in both the internal and external jugular venous blood of migraine patients during attacks. Experimental evidence demonstrated that when released from C-type sensory neurons in inflammatory pain models, it differentially induced expression of neutrophil chemotactic chemokine IL-8, but not monocyte chemotactic chemokine MCP-1 or lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated in migraine. DESIGN/METHODS: Eight migraine without aura patients were admitted to the hospital during the attacks. Internal jugular venous blood samples were taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after attack onset, and within 2 hours from its cessation. The levels of the sensory neuropeptide calcitonin gene-related peptide and the messenger cyclic adenosine monophosphate were measured by RIA method, and those of IL-8, MCP-1, and RANTES were measured by ELISA method. RESULTS: Higher calcitonin gene-related peptide levels were found in the internal jugular venous blood of migraine without aura patients compared with the time of catheter insertion (ANOVA: P<.0001) with a peak at the first hour (52.6+/-9.2 ng/mL). A transient increase in IL-8 was observed at the 2nd and 4th hours (P<.01 and P<.002, respectively), whereas no changes in the levels of MCP-1 and RANTES were found at any time of the study. The increase in IL-8 was accompanied by a parallel increase in cyclic adenosine monophosphate. CONCLUSIONS: The present study confirms previous findings of an increase in calcitonin gene-related peptide in internal jugular venous blood of migraine without aura patients during attacks. The transient increase in the levels of IL-8 concurs with the results of recent experimental research showing a calcitonin gene-related peptide-induced activation of IL-8 gene expression, but not RANTES and MCP-1, via the transcriptional factor AP-2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL-8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation.