Long-term acetyl-L-carnitine treatment in Alzheimer's disease.

In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.

Effects of thiopentone and mannitol on cerebral perfusion pressure and E.E.G. in head injured patients with intracranial hypertension.

The effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and EEG monitored by Cerebral Function Monitor (CFM) were compared after bolus administration of mannitol (n = 55) and thiopentone (n = 67) to control intracranial hypertension in 18 severely head injured patients. Mannitol increased CPP in 89% of occasions and thiopentone in only 54% (p < 0.001). Thiopentone caused a mean increase in CPP +0.6 kPa (+5.0 +/- 1.6 mmHg) when the minimum pre-bolus voltage of CFM was above 4 microV and a fall in CPP -0.5 kPa (-4.1 +/- 1.6 mmHg) when cortical electrical activity was already severely depressed (p < 0.0002). When pre-bolus CFM was below 4 microV mannitol was superior to thiopentone. This different effect on CPP was due to a significantly greater fall in mean arterial pressure in the thiopentone sub-group -1.6 versus -0.3 kPa (-12.4 +/- 1.5 mmHg, -2.8 +/- 1.2 mmHg; p < 0.001). Severe and unpredictable hypotension occurred, particularly in the thiopentone low CFM sub-group. This symptomatic therapy seems inadequate but a targeted treatment of intracranial hypertension could be possible only with a more sophisticated monitoring, including continuous data on cerebral blood flow and adequacy to metabolic demand.

[Continuous monitoring of O2 saturation in cerebral blood. A guide for the nursing of brain trauma patients in coma]. / Monitoraggio continuo della saturazione di O2 del sangue refluo cerebrale. Una guida del nursing nel traumatizzato cranico in coma.

Manual ventilation is frequently performed by nurses to control increases in intracranial pressure (ICP) or during physiotherapy in head injured comatose patients. The effects of manual ventilation (n = 251) on ICP, cerebral perfusion pressure (CPP) and EEG have been studied in 18 mechanically ventilated patients. A fall in ICP was easily obtained but a fall in arterial blood pressure was often present at the same time. Thus a reduction in CPP resulted in 36% of occasions. Prophylactic boluses of thiopental (n = 67) before noxious stimuli obtained a fall in ICP in 99% of occasions but resulted in a decrease in CPP in 46%. The fall in ICP, due to the decrease in cerebral blood flow (CBF) by hypocapnia or metabolic depression and/or arterial hypotension, may be beneficial in hyperaemic brains but may precipitate cerebral hypoxia in ischaemic lesions. Relevant information about cortical metabolism (CMR) may be obtained from EEG monitoring by Cerebral Function Monitor but, unfortunately, no data about CBF are clinically available. The Authors suggest that the continuous monitoring of jugular bulb oxygen saturation (SjO2) may offer a clinically useful index of CBF adequacy to CMR. Findings from a preliminary study in 5 patients demonstrate that a severe decrease in SjO2 has been frequently caused by manual ventilation, hypothetically related to severe cerebral ischemia. High levels of SjO2 have been induced by endotracheal suction and physiotherapy, probably related to severe hyperemia. As prevention of ischaemic and hyperaemic insults is a major goal of treatment, the A. suggest that these undesirable effects of nursing might be avoided if nurses could take advantage of continuous monitoring of SjO2.

An example of a clinical trial in patients with Alzheimer's disease: some methodological issues.

UNLABELLED: In ten Italian centers--hospitals and geriatric institutions--130 outpatients and inpatients with a diagnosis of Alzheimer's disease were recruited for a randomized, double blind, placebo controlled clinical trial with 1-acetylcarnitine. In planning the trial, we had to deal with some important and largely open issues. DIAGNOSIS: we decided not to use neuropsychological tests (NPT) in the diagnostic process, both for the unknown risk of false positive and false negative rate and to improve the feasibility of the trial. FOLLOW-UP: it must be representative of the disease and consequently we chose to follow the patients for one year (assessment at baseline, 3rd, 6th and 12th month) in spite of a possible high rate of drop-outs. ASSESSMENT: to assess the patients' outcome we used NPT and behavioural scales. However, the validity, reliability and feasibility of these instruments are rarely discussed and their usefulness as indicators of the relevant aspects of the disease needs a careful evaluation. STATISTICAL ANALYSIS: in this type of trial there is both a high risk of alpha-error, in view of the high number of NPT and behavioural scales used to assess the drug efficacy, and a high risk of beta-error connected with the usually small sample size. Thus, the role of small trials in defining the risk/benefit ratio of a treatment needs to be discussed.