Michal Bar

Tolerability and safety of perampanel: Two randomized dose-escalation studies

Krauss GL, Bar M, Biton V, Klapper JA, Rektor I, Vaiciene‐Magistris N, Squillacote D, Kumar D. Tolerability and safety of perampanel: two randomized dose‐escalation studies. Acta Neurol Scand: 2012: 125: 8–15. 
© 2011 John Wiley & Sons A/S.

Perampanel Study 207: Long-term open-label evaluation in patients with epilepsy

Evaluate interim long‐term tolerability, safety and efficacy of adjunctive perampanel, a novel α‐amino‐3‐hydroxy‐5‐methyl‐5‐isoxazolepropionic acid (AMPA)‐receptor antagonist, in patients with refractory partial‐onset seizures.

Epidemiological of and risk factors for Alzheimer‘s disease: A review

BACKGROUND Alzheimers disease (AD) is the most common form of dementia. It is a degenerative, incurable and terminal disease. The increasing prevalence of AD is, among other reasons, due to population aging, which is, to a certain extent, seen worldwide. Continuous advances in health care keep increasing life expectancy. Official statistics are likely to significantly underestimate the actual prevalence of AD. Alzheimers disease represents an important public health problem. Its aetiology is still unknown and for this reason, it is necessary to study all potential risk factors which may contribute to the development of this disease. METHODS We searched original and review articles addressing Alzheimers disease using key words Alzheimers disease, epidemiology, risk factors and prevention. We found and used one hundred and four references. CONCLUSIONS Based on epidemiological studies, genetic studies, neuroimaging methods and neuropathology research, three basic etiological hypotheses of the development of AD have been formulated: genetic, vascular and psychosocial. At present, the level of evidence is insufficient for the etiological role of other factors, such as nutrition, occupational exposure to various substances and inflammation. From the point of view of early diagnosis and application of primary or secondary prevention principles, genetic factors are the most important.

Safety and Efficacy of the Sonographic Acceleration of the Middle Cerebral Artery Recanalization: Results of the pilot Thrombotripsy Study

The aim was to demonstrate the safety and efficacy of continuous ultrasound monitoring of the artery occlusion area (sonothrombotripsy) in patients with acute middle cerebral artery (MCA) occlusion. A total of 52 consecutive patients with acute MCA occlusion were included in the thrombotripsy group. Doppler monitoring of the region of occlusion was performed for up to 45 min. The control group was created from the NAIS study database. Patients were matched for their vascular status, age, sex, artery occlusion, NIHSS at admission, rt-PA treatment and time to the first ultrasound examination. The number of recanalized arteries at 6 and 24 h after the onset of symptoms, the number of independent patients (mRS 0-2 versus 3-6) after 90 d, and the number of serious adverse events were statistically evaluated. In the thrombotripsy group, 19 patients (36.5%) had complete recanalization and 27 (51.9%) patients had partial recanalization at 1 h after the start of the TCCS monitoring. Higher recanalization rates at 6 and 24 h after stoke onset were also seen compared with controls (69.2% versus 7.7% and 92.3% versus 61.5% complete recanalizations, respectively, p < 0.05). Independence (mRS 0-2) at day 90 was achieved by 61.5% of the thrombotripsy patients and 32.7% controls, p < 0.05, odds ratio 1.88 (95% confidence interval = 1.23 - 2.90). In both groups, two symptomatic intracerebral hemorrhages and one symptomatic brain edema occurred. Sonothrombotripsy with diagnostic transcranial duplex technology is safe and may offer benefit in addition to standard of care stroke treatment.

Claustrum damage and refractory status epilepticus following febrile illness

Objective: To characterize the clinical, EEG, and brain imaging findings in an adult case series of patients with de novo refractory status epilepticus (SE) occurring after a febrile illness. Methods: A retrospective study (2010–2013) was undertaken with the following inclusion criteria: (1) previously healthy adults with refractory SE; (2) seizure onset 0–21 days after a febrile illness; (3) lacking evidence of infectious agents in CSF; (4) no history of seizures (febrile or afebrile) or previous or concomitant neurologic disorder. Results: Among 155 refractory SE cases observed in the study period, 6 patients (17–35 years old) fulfilled the inclusion criteria. Confusion and stupor were the most common symptoms at disease onset, followed after a few days by acute repeated seizures that were uncountable in all but one. Seizures consisted of focal motor/myoclonic phenomena with subsequent generalization. Antiepileptic drugs failed in every patient to control seizures, with all participants requiring intensive care unit admission. Barbiturate coma with burst-suppression pattern was applied in 4 out of 6 patients for 5–14 days. One participant died in the acute phase. In each patient, we observed a reversible bilateral claustrum MRI hyperintensity on T2-weighted sequences, without restricted diffusion, time-related with SE. All patients had negative multiple neural antibodies testing. Four out of 5 surviving patients developed chronic epilepsy. Conclusions: This is a hypothesis-generating study of a preliminary nature supporting the role of the claustrum in postfebrile de novo SE; future prospective studies are needed to delineate the specificity of this condition, its pathogenesis, and the etiology.

Colour Doppler imaging evaluation of blood flow parameters in the ophthalmic artery in acute and chronic phases of optic neuritis in multiple sclerosis.

Purpose:  Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS). It is caused by the immune‐mediated inflammation of the optic nerve. Some vascular factors that may influence blood flow in the ophthalmic artery (OA) have also been suggested as factors in the pathogenesis of ON. The purpose of our study was to evaluate blood flow velocities and resistance (RI) and pulsatile (PI) indices in the OA in both orbits in patients in the acute and chronic phases of unilateral ON and to compare these with equivalent findings in healthy control subjects.

Distal enlargement of the optic nerve sheath in the hyperacute stage of intracerebral haemorrhage

Aims Optic nerve sheath diameter (ONSD) enlargement is detectable in patients with increased intracranial pressure. The aim was to detect an enlargement of the ONSD using optic nerve sonography in patients with acute intracerebral haemorrhage (ICH) within 6 h of the onset of symptoms. Methods Thirty-one acute ICH patients, 15 age-matched acute ischaemic stroke patients and 16 age-matched healthy volunteers were enrolled consecutively in this prospective bi-centre observational study. All acute stroke patients underwent brain CT, optic nerve sonography and transcranial colour-coded duplex sonography (TCCS) at admission within 6 h of stroke onset. The ONSD both 3.0 and 12.0 mm behind the globe using optic nerve sonography were recorded and statistically evaluated, as were age, sex, haemorrhage volume and midline shift measured by CT, and blood flow velocities in both middle cerebral arteries using TCCS. Results In acute ICH patients, a significant enlargement of ONSD was detected (p<0.0083). The best cut-off point to predict ICH volume >2.5 cm3 was the relative ONSD enlargement of >0.66 mm (>21 %), with 90.3% accuracy and kappa coefficient 0.760 (95% CI 0.509 to 1.000). Conclusions Sonographically measured enlargement of the ONSD may already be detectable in the hyperacute stage of increased intracranial pressure.

CHANGES IN HEMOCOAGULATION IN ACUTE STROKE PATIENTS AFTER ONE-HOUR SONO-THROMBOLYSIS USING A DIAGNOSTIC PROBE

The aim was to monitor the changes in hemocoagulation parameters in acute ischemic stroke (AIS) patients after sono-thrombolysis of the occluded middle cerebral artery using a duplex transcranial probe with 2.0-MHz frequency in Doppler mode. Sixteen AIS patients indicated for intravenous thrombolysis (IVT) (8 males; mean age 68.3 +/- 7.1 y) and 16 AIS patients contraindicated for IVT (11 males; mean age 67.9 +/- 7.9 y) were randomized for sono-thrombolysis (8 + 8 patients) or standard treatment (control group) (8 + 8 patients). The significant decrease of plasminogen activator inhibitor-1, plasminogen and alpha-2-antiplasmin activity by a mean of 60, 32 and 24%, respectively, and the increase of tissue plasminogen activator by a mean of 56% was found after sono-thrombolysis when compared with control group (p < 0.0125); these changes were more evident in patients treated with a combination of sono-thrombolysis and IVT (79, 38, 50 and 82%, respectively) than in patients treated by sono-thrombolysis alone (34, 13, 17 and 30%, respectively).

Diagnosis of Recanalization of the Intracranial Artery Has Poor Inter-Rater Reliability

BACKGROUND AND PURPOSE: Recanalization is the important outcome measure for acute stroke therapy. Several methods of recanalization assessment are used in clinical practice, but few studies have addressed their reliability. We, therefore, sought to assess interobserver reliability of the diagnosis of intracranial artery recanalization following intervention by using TIMI criteria. MATERIALS AND METHODS: The digital angiography scans of all patients with acute ischemic stroke during 2009 undergoing DSA and endovascular procedures at Ostrava University Hospital were assessed in the study. Images were retrospectively evaluated for intracranial artery recanalization on the TIMI scale by 2 experienced neuroradiologists who were blinded to clinical findings and to each other. RESULTS: The angiography scans of 43 patients (16 females; age, 70.5 ± 14 years; median baseline NIHSS score, 15 [IQR, 11–18]) were retrospectively evaluated in our study. At 3 months, 27% of patients had mRS scores ≤ 2 and mortality was 18%. Two radiologists diagnosed TIMI grades as follows: TIMI 0, 16%, and 16%; TIMI 1, 21%, and 8%; TIMI 2a, 32% and 29%; TIMI 2b, 13% and 16%; TIMI 3, 18, and 31%. Interobserver agreement for recanalization was weighted κ = 0.4 (95% CI, 0.2–0.6). CONCLUSIONS: The diagnosis of recanalization after interventional procedures was found to have poor interobserver agreement between 2 experienced neuroradiologists. TIMI criteria, therefore, do not permit reliable comparison of the efficacy of recanalization therapy among different studies.

Transcranial Duplex Sonography and CT Angiography in Acute Stroke Patients

Acute occlusion of cervical or intracranial arteries is the most common cause of ischemic stroke (IS). The aims of the current study were to compare the occurrence of acute pathologic findings in intracranial arteries using transcranial color‐coded sonography (TCCS) and computed tomographic angiography (CTA) performed within 3 hours of IS onset and to assess the correlation between the vascular findings on admission and the patients clinical state on admission and 3 months after the IS. Forty‐five consecutive patients with an acute IS were included in the prospective study during an 18‐month period. All patients underwent CTA and TCCS within the first 3 hours of symptom onset. A high rate of pathologic findings in the intracranial circulation was found (70.9% in CTA and 77.4% in TCCS examinations). The CTA and TCCS findings with respect to the intracranial arteries were consistent in 87.1% of cases (Cohens κ, .797). The sensitivity, specificity, and positive and negative predictive values achieved with TCCS in patients with middle cerebral artery main stem occlusion were 92.3%, 94.4%, and 92.3% and 94.4%, respectively. There was no correlation between the patients clinical status on admission and 3 months after the onset of the IS and the CTA or the TCCS findings (P > .1 in all cases). A substantial agreement was found between TCCS and CTA in the detection of pathologic findings in intracranial vessels in acute stroke patients. Both methods can be used for this purpose.