Atrophic enlargement of CSF volume after subarachnoid hemorrhage: correlation with neuropsychological outcome.

BACKGROUND AND PURPOSE: Ventricular dilation and sulcal enlargement are common sequelae after aSAH. Our aim was to quantify the late ventricular dilation and volumes of the CSF spaces after aSAH and to determine if they correlate with neurologic and cognitive impairments frequently detected in these patients. MATERIALS AND METHODS: 3D T1-weighted images needed for volumetry were available in 76 patients 1 year after aSAH, along with 75 neuropsychological assessments. Volumes of CSF segments and ICV were quantified by SPM in 76 patients and 30 control subjects to determine CSF/ICV ratios. The mCMI was calculated to roughly evaluate the ventricular dilation. The contributing factors for enlarged ventricles and CSF volumes were reviewed from radiologic, clinical, and neuropsychological perspectives. RESULTS: The mCMI was higher in patients with aSAH (0.23 +/- 0.06) compared with control subjects (0.20 +/- 0.04; P = .020). In line with these planimetric measurements, the SPM-based CSF/ICV ratios were higher in patients with aSAH (35.58 +/- 7.0) than in control subjects (30.36 +/- 6.25; P = .001). Preoperative hydrocephalus, higher HH and Fisher grades, and focal parenchymal lesions on brain MR imaging, but not the treatment technique, were associated with ventricular enlargement. The clinical outcome and presence of neuropsychological deficits correlated significantly with CSF enlargement. CONCLUSIONS: Ventricular and sulcal enlargement, together with reduced GM volumes, after aSAH may indicate general atrophy rather than hydrocephalus. Enlarged CSF spaces correlate with cognitive deficits after aSAH. A simple measure, mCMI proved to be a feasible tool to assess the diffuse atrophic brain damage after aSAH.

Heterogeneity of cerebral blood flow in symptomatic patients undergoing carotid endarterectomy.

There is still controversy concerning which patients with asymptomatic carotid stenosis or symptomatic moderate stenosis are likely to benefit from carotid endarterectomy. The surgical candidates for carotid endarterectomy should have a high risk for stroke, but a low risk for operative complications. Therefore, new effective patient selection strategies, including haemodynamic testing, schemes of risk stratification and pre-operative cardiac testing, are under investigation. To improve haemodynamic assessment of patients with carotid artery stenosis, we evaluated a novel global cerebral blood flow (CBF) heterogeneity index at rest and after acetazolamide injection in patients undergoing carotid endarterectomy. CBF heterogeneity index was measured in 15 patients by using basal and acetazolamide enhanced 99mTc-HMPAO SPET both before and 1 month after surgery. CBF heterogeneity index was calculated as the coefficient of variation of a total of 44 cerebral regions representing mainly both ipsi- and contralateral grey matter. A high linear correlation was observed between CBF heterogeneity index and ipsilateral carotid stenosis degree (r=0.74, P=0.003). Before surgery, CBF heterogeneity index increased significantly after acetazolamide injection when compared to the basal condition (from 7.0+/-1.5 to 8.3+/-1.7%, P=0.008). This response disappeared after carotid endarterectomy. When compared to pure asymmetry of CBF (ipsi/contralateral CBF ratio), the CBF heterogeneity index seemed to reflect, more sensitively, the haemodynamic effects of carotid endarterectomy. The CBF heterogeneity index after acetazolamide injection is a sensitive marker of the haemodynamic consequences of carotid artery stenosis and its operative treatment.

Predictors of seizure outcome in newly diagnosed partial epilepsy: memory performance as a prognostic factor.

The epilepsy patients whose seizures will prove to be refractory should be identified as early as possible, and thus the need for new prognostic factors of intractable epilepsy is evident. The aim of the study was to investigate predictors of seizure outcome in a multivariate analysis. Neurological, electroencephalography (EEG) and neuropsychological variables were analyzed as potential predictors of epilepsy. Eighty-nine newly diagnosed adult patients with partial epilepsy were, after a prospective 2-year follow-up period, categorized into one of the two groups: patients with satisfactorily controlled epilepsy, and patients with refractory epilepsy. Six variables predicted 2-year seizure outcome: presence of spike focus in EEG, partial complex or mixed seizure type, remote symptomatic etiology, moderately impaired memory performance in immediate recall and in delayed recognition of the word list, and age at the time of diagnosis. The correct seizure outcome could be predicted with the model in 94% of newly diagnosed epilepsy patients. The presence of verbal memory impairment at the time of the diagnosis of partial epilepsy is a significant predictor of seizure outcome and, together with clinical and EEG variables, it predicts seizure outcome in the majority of the patients. Memory performance as a prognostic factor is of most value in patients with risk of refractory epilepsy and when used in a multidisciplinary setting.

Subclinical cerebral complications after coronary artery bypass grafting: prospective analysis with magnetic resonance imaging, quantitative electroencephalography, and neuropsychological assessment.

OBJECTIVE: To analyze the frequency and severity of subclinical cerebral complications associated with coronary artery bypass grafting (CABG). DESIGN: A prospective controlled study using preoperative and postoperative magnetic resonance imaging (MRI) of the brain, quantitative electroencephalography (QEEG), and detailed neuropsychological and neurologic examinations as potentially sensitive indicators of subclinical cerebral injury associated with CABG. SETTING: Multimodality evaluation in a tertiary care unit (Kuopio University Hospital, Kuopio, Finland). PATIENTS: Thirty-eight patients undergoing elective CABG and 20 control patients undergoing other major vascular surgery, mostly operations on the abdominal aorta. MAIN OUTCOME MEASURES: Coronary artery bypass grafting-associated cerebral complications assessed preoperatively and postoperatively by brain MRI, QEEG, detailed neurologic examination, and a neuropsychological test battery that evaluates cognitive functions in major areas known to be vulnerable to organic impairment (learning and memory, attention, flexible mental processing, and psychomotor speed). RESULTS: There were no major neurologic complications. A mild hemisyndrome developed in 1 patient who underwent CABG and in 1 control patient. Overall, there was no decline in mean cognitive performance 3 months after surgery. Electroencephalographic slowing of 0.5 Hz or more in at least 2 channels occurred in 11 patients who underwent CABG and in 1 control patient (P=.03). The postoperative brain MRI scan revealed new small ischemic lesions in 8 patients (21%) in the CABG group but in none of the control group (P=.03). These new cerebral MRI lesions did not explain deterioration in neuropsychological test performance or the QEEG slowing. CONCLUSIONS: Coronary artery bypass grafting causes more QEEG alterations and small ischemic cerebral lesions that are detectable by MRI than does other major vascular surgery. The effect is mainly subclinical, because no statistically significant deterioration in mean neuropsychological test performance was detected.

Long-term cognitive and EEG effects of tiagabine in drug-resistant partial epilepsy.

A new anti-epileptic drug, tiagabine, is a potent inhibitor of GABA uptake into neurons and glia. Tiagabine has shown promising efficacy and safety profiles as add-on treatment for partial seizures. We evaluated the long-term effects of tiagabine on cognition and EEG in 37 patients with partial epilepsy. The study protocol consisted of a randomized, double-blind, placebo-controlled, parallel-group add-on study and an open-label extension study. During the 3 month double-blind phase at low doses (30 mg/day) tiagabine treatment did not cause any cognitive or EEG changes as compared with placebo. Tiagabine treatment did not cause deterioration in cognitive performance or produce any rhythmic slow-wave activity or other constant, new abnormalities on EEG during longer follow-up with successful treatment on higher doses after 6-12 months (mean 65.7 mg/day, range 30-80 mg/day) and after 18-24 months (mean dose 67.6 mg/day, range 24-80 mg/day). The daily dosages in the long-term follow-up of the present study are higher than in the previous reports.

Cognitive Adverse Effects of Antiepileptic Drugs : Incidence, Mechanisms and Therapeutic Implications.

Several early studies suggested that differences exist between antiepileptic drugs (AEDs) in terms of their propensity to cause adverse effects on cognitive functions, favouring carbamazepine over phenobarbital (phenobarbitone), phenytoin and valproic acid (sodium valproate). The combined results of recent studies in patients and healthy volunteers reveal that at therapeutic serum concentrations phenobarbital, phenytoin, carbamazepine, oxcarbazepine and valproic acid produce nearly comparable adverse effects on higher cognitive functions.The newer AEDs (with the exception of zonisamide and topiramate) appear to induced fewer cognitive adverse effects than the older agents. Furthermore, there is limited evidence that gabapentin, lamotrigine and vigabatrin may have beneficial effects on cognitive function. Some of the newer AEDs may also have neuroprotective effects that can prevent seizure-induced neuronal damage, and so reduce cognitive dysfunction. This is an important clinical consideration, as even modest differences between older and newer AEDs are relevant for patients.

Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study.

OBJECTIVE: To evaluate the efficacy, safety, and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy. DESIGN: Open, randomized, controlled design. Follow-up period of 12 months. SETTING: University hospital with an epilepsy center. PATIENTS: A total of 100 patients, aged 15 to 64 years, classified as suffering from partial seizures and/or generalized tonic-clonic seizures were randomized to either vigabatrin or carbamazepine monotherapy. Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures. OUTCOME MEASURES: To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine, the drug success rate (ie, the proportion of patients continuing successful treatment with the randomly assigned drug) after 12 months of steady-state treatment was used. To evaluate the safety of the drugs in addition to reported side effects, visual evoked potential recordings and neuropsychological evaluation were performed during follow-up. RESULTS: During the 12-month follow-up period, 60% of patients receiving vigabatrin and carbamazepine were treated successfully. Vigabatrin caused fewer side effects that required discontinuation of therapy. However, vigabatrin had to be discontinuated more often owing to lack of efficacy, and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures. Vigabatrin had no detrimental effects on cognitive functions. Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin. CONCLUSION: Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine.

Verbal learning and memory in newly diagnosed partial epilepsy.

Verbal learning and memory of 56 adults with newly diagnosed partial epilepsy and no other known brain pathology were compared with memory performance of a normal control group. Memory was evaluated with a list learning test and with recall of logical prose under both immediate and delayed recall conditions. The patients and the controls did not differ in immediate and delayed recall of logical prose. Also learning and immediate recall of the word list was comparable in both groups. After delay the patients recalled fewer words than the control group (P < 0.001), and the percent retention of words was lower in the patients (P < 0.001). The patients with newly diagnosed epilepsy more frequently exhibited mild verbal memory dysfunction as shown in delayed recall of word list. Moderate memory impairment is seen in a group of patients who have deficits in immediate and delayed memory. Follow-up is needed to find out whether patients with memory deficits at the time of diagnosis are those who develop intractable chronic epilepsy.

Memory and attention in newly diagnosed epileptic seizure disorder.

Interictal disturbances of memory and attention were evaluated in 74 adults with newly-diagnosed untreated epileptic seizures and no other known brain pathology. In approximately 30% of the patients with cryptogenic seizures, the average memory and attention scores indicated subtle dysfunction compared with normal control group. The patients had difficulties in tasks requiring memory, sustained attention and flexible mental processing, whereas they had normal attention span, simple speed of tracking and simple psychomotor speed. The memory difficulties may be related to attentional dysfunction leading to impaired or slowed initial encoding of memory trace, and also to a deficit in storing process and hippocampal dysfunction. These findings could have important implications for establishing criteria for identifying patients who develop chronic epilepsy and who thereby would benefit from early therapeutic intervention.

Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up.

We evaluated the effect of initial oxcarbazepine (OXC) monotherapy on memory, attention and simple psychomotor speed in 14 patients; 15 patients with initial phenytoin (PHT) monotherapy served as reference patients. Neuropsychological assessments were performed before starting the treatment and after 6 and 12 months follow-up with steady-state drug treatment. Differential cognitive effects of OXC and PHT were not apparent in our study. As the efficacy of present antiepileptic drugs in adult epilepsy is analogous, the choice of drug is determined by the comparative side effects of the drugs. In the present study the number of successfully treated patients was similar in both OXC and PHT groups. As far as cognitive side effects are concerned our results revealed no evidence favoring either antiepileptic over the other.

Randomized controlled pilot study of vigabatrin versus carbamazepine monotherapy in newly diagnosed patients with epilepsy: an interim report.

At present, 34 patients aged 15 to 63 years with newly diagnosed epilepsy have been randomly assigned to vigabatrin (n = 17) or carbamazepine (n = 17). Evaluation of clinical data, neuropsychological assessment, quantitative spectral electroencephalogram (EEG), and somatosensory- and visual-evoked potentials at baseline and after a 3 months' maintenance phase are presented for 12 patients on vigabatrin and for 11 patients on carbamazepine. Among these patients, retention rate in the maintenance phase of the study is 75% for vigabatrin patients (two noncompliant patients and one nonresponder dropped out) followed up for a mean of 11 months (range, 5 to 16 months). The retention rate for carbamazepine is 100% for the 11 patients, followed up for a mean of 9 months (range, 3 to 17 months). Patients receiving vigabatrin showed significant improvements in sustained concentration and tasks requiring flexible mental processing after the 3-month maintenance period, compared to baseline. In the carbamazepine group, there was improvement only in delayed list recall, and in contrast, errors in visuomotor tasks requiring processing increased significantly. Patients on carbamazepine demonstrated slowed occipital mean frequencies, but vigabatrin treatment was not associated with any significant quantitative EEG changes. Significant prolongation of somatosensory-evoked potential N19 latencies was seen with both carbamazepine and vigabatrin.

Somatostatin-like immunoreactivity in cerebrospinal fluid of patients with complex partial epilepsy.

To investigate the role of somatostatin in human epilepsy, we measured somatostatin-like immunoreactivity (SLI) by radioimmunoassay of the cerebrospinal fluid (CSF) of 60 patients with complex partial seizures (CPS), 5 patients with other neurological diseases (OND), and 23 controls. The SLI levels were measured in groups of epileptic patients that differed in their history of disease, electroencephalogram (EEG), computerized tomography (CT) finding, psychological test scores, or anticonvulsant medication. SLI was lower in the epilepsy group (p less than 0.05) than in the controls. Patients with carbamazepine-clonazepam therapy had lower SLI than did other epileptics (p less than 0.02) or controls (p less than 0.005). Patients with central atrophy (p less than 0.01) in CT and infection (p less than 0.01) as an etiologic cause of epilepsy also seemed to have lower levels of SLI in the CSF than did other epileptics. No correlation was found between psychological memory scores and SLI levels in the CSF of patients with CPS. The present study shows that somatostatin levels are lowered in the CSF of epileptic patients, possibly owing to the lowered somatostatin content or the decreased number of somatostatinergic nerve cells in the epileptic human brain. However, studies in unmedicated patients with different types of seizures are needed to further clarify the possible role of somatostatin in human epilepsy.