Carlo Loeb

Dementia associated with lacunar infarction.

Background and Purpose: The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence. Methods: One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke. Results: Twenty-five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p<0.009) and in subjects who underwent new focal cerebrovascular episodes (p<0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups. Conclusions: Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia.

Vascular dementia: still a debatable entity?

Vascular dementia (VAD) is currently considered to be the second most common cause of dementia in Europe and the USA, second to dementia of the Alzheimers type (DAT). However, in Asia and many developing countries the incidence of VAD exceeds that of DAT. The positive clinical diagnostic workup for VAD requires six steps: (1) clear-cut quantitative assessment of cognitive deficits utilizing standard neuropsychological tests to establish and quantify the dementia syndrome and rule out pseudo-dementia OF depression; (2) ascertaining the presence of risk factors for stroke; (3) identifying cerebral vascular lesions by neuroimaging (MRI, Iodine or Xenon contrasted CT, PET and SPECT); (4) exclusion of other causes of dementia; (5) differential diagnosis of possible, probable or definite VAD versus DAT and ascertaining when there are mixtures of the two; and (6) temporal identification of causality between onset and progression of the dementia with identified cerebral vascular lesions. There are eight subtypes of VAD: (1) multi-infarct dementias. These are due to large cerebral emboli, and are usually readily identifiable; (2) strategically placed infarctions causing dementia; (3) multiple subcortical lacunar lesions. Patients with these develop VAD at least five to twenty-five times more frequently than those in age-matched general population samples; (4) Binswangers disease (arteriosclerotic subcortical leuko-encephalopathy). This form is rare. Neuroimaging confirms the diagnosis during life but the diagnosis can not be made by neuroimaging alone; (5) mixtures of two or more of above VAD subtypes; (6) hemorrhagic lesions causing dementia; (7) subcortical dementias due to cerebral autosomally dominant arteriolopathy with subcortical infarcts and leuko-encephalopathy (CADASIL), or to familial amyloid angiopathies and coagulopathies all of which present with multiple subcortical lacunar lesions similar to Binswangers disease; (8) mixtures of DAT and VAD. The clinical significance of leukoaraiosis and its suspected relationships to VAD remains to be better established. The presence of ischemic infarctions, single or multiple large or multiple small (lacunar) by neuroimaging are necessary for the diagnosis of VAD, but identifying their presence, by neuroimaging alone, does not permit the diagnosis of dementia which can only be established by neuropsychological assessments. VAD is a clinical entity, identifiable in at least 30-70% of patients after strokes but mechanisms responsible for the cognitive impairments are complex. Some of these mechanisms are incompletely understood but provide subjects for important future research.

Intellectual impairment and cerebral lesions in multiple cerebral infarcts. A clinical-computed tomography study.

The relation between cerebral lesions studied by computed tomography and the dementia syndrome has been evaluated in 40 patients with multi-infarct dementia, in 44 nondemented subjects with multiple infarcts, and in 30 controls matched for age and sex. Our study of the volume of ischemic lesions showed a slightly greater loss of cerebral substance in patients with multi-infarct dementia than in nondemented subjects with multiple infarcts, particularly in subjects with unilateral focal lesions and in patients with bilateral multiple cortical and subcortical lesions. The dementia syndrome was significantly associated with multiple locations of lesions in the thalamic and cortical areas supplied by the middle cerebral arteries. Moreover, patients with the dementia syndrome showed a significantly higher degree of cerebral atrophy than nondemented subjects and controls as evaluated by measurements of ventricular size, area of ventricular space, and area of subarachnoid space.

Somatic afferent transmission and cortical responsiveness during natural sleep and arousal in the cat

Abstract Both peripherally and centrally evoked somatic responses vary greatly in amplitude according to the level of vigilance. This effect is due both to modifications of afferent transmission along the somatic pathways and to variations in responsiveness of the cortical neurones. In particular: 1. (a) the afferent transmission at the level of the 1st station (gracilis and cuneatus nuclei) does not seem to be affected by the depth of sleep, being unchanged during deep sleep as compared to light sleep; during arousal it may vary greatly according to concomitant behavioural changes; 2. (b) the afferent transmission at the level of the 2nd station (nucleus ventro-postero-lateralis of the thalamus) is constantly affected by the depth of sleep, being maximal during deep sleep; during arousal it can appear either facilitated or depressed according to the depth of the preceding spell of sleep; 3. (c) somatic cortical responsiveness is maximal during light sleep, being apparently depressed during deep sleep and arousal.

Clinical Criteria for the Diagnosis of Vascular Dementia

The clinical diagnosis of dementia includes medical history, neurological examination, psychiatric interview and dementia scale. The identification of conditions producing dementia can only be achieved by adding to the clinical information the data gathered from ancillary investigations. The usual ancillary diagnostic investigations (biochemical tests, cerebrospinal fluid (CSF), EEG, CT, MRI, angiography) can rather easily identify brain disorders due to tumors, vascular malformations, hematomas, infections, toxins and drugs, deficiency diseases, normal-pressure hydrocephalus, metabolic and endocrine derangements. The differential diagnosis between degenerative and vascular dementia needs laboratory tests such as CSF, EEG, Somatosensory Evoked Potentials, CT (which constitutes a major role in a modified ischemic score) and MRI. The three final diagnostic labels are possible, probable and definite vascular dementia, which include clinical features and laboratory investigations concurrently confirming the diagnosis. If ancillary investigations fail to show multiple infarct lesions or if mixed forms are suspected an unequivocal diagnosis can be made only on histopathological evidence.

Risk factors in lacunar syndromes: a case‐control study

ABSTRACT— The association between some hypothetical risk factors (previous TIA, hypertension, ECG ischemic abnormalities, diabetes, cigarette smoking, atrial fibrillation, hypercholesterolemia, hypertriglyceridemia, high hematocrit) and lacunar syndromes has been evaluated by a matched sample case‐control study involving 108 consecutive, incident cases with lacunar syndrome and 216 hospital control subjects, matched for sex and age. A significant increase of Relative Risk (RR) has been shown for: 1. Previous history of TIA; 2. Hypertension; 3. Smoking; 4. Diabetes. No relevance was shown for: 1. Atrial fibrillation; 2. Hypercholesterolemia; 3. Hypertriglyceridemia; 4. High hematocrit. The analysis of the triplets of subjects (1 case + 2 controls) without hypertension showed a significant RR increase for: 1. Previous history of TIA; 2. Ischemic cardiac abnormalities; 3. Atrial fibrillation. Such findings support the hypothesis that, in a minority of cases with lacunar syndrome, the pathogenetic mechanism could be different from occlusion of penetrating arteries in hypertensive patients.

Vigabatrin in complex partial seizures: a long-term study.

The efficacy and safety of oral vigabatrin (VGB) as add-on therapy in the long-term treatment of poorly controlled epilepsy were evaluated in 19 patients with complex partial seizures, either with or without secondary generalization. The study was run with a single-blind, placebo-controlled, crossover design, and included 2 months of placebo and 13-15 months of treatment with VGB, at doses ranging from 1 to 4 g/day. Of the 14 patients who completed the trial, 2 were seizure free, in 5 seizure frequency dropped by more than 75% and in another 5 by more than 50% with respect to baseline. The decrease in seizure frequency in the group as a whole was significant at all observation points of the trial. Three patients were not entered into the long-term phase due to lack of improvement (an increase in seizure frequency was observed in one of them), and 2 were excluded later because improvement disappeared leading to unauthorized changes in comedication. Side effects were mild and never caused discontinuation of treatment. In conclusion, VGB showed a remarkable efficacy and safety in the long-term treatment of complex partial seizures.

Abnormal tau‐reactive filaments in olfactory mucosa in biopsy specimens of patients with probable Alzheimer's disease

We immunocytochemically analyzed pieces of olfactory mucosa removed by biopsy in 8 patients with probable Alzheimers disease (AD) and 6 age-matched controls, with tau and ubiquitin antisera. There were tau-reactive and, partially, ubiquitin-reactive dystrophic neurites in the lamina propria of olfactory mucosa in all AD cases. The tau-reactive neurites contained abnormal straight filaments, 15 to 18 nm in diameter, morphologically identical to those found in AD cerebral brain tissue obtained at autopsy. Tau and ubiquitin immunoreactivity were absent in controls. If these neuritic alterations are confirmed in a larger number of cases, analysis of olfactory mucosa may increase the current reliability of clinical diagnosis of AD.

Electroencephalographic changes during the state of coma

Abstract This study is based upon 25 selected comatose subjects investigated from the clinical, EEG, and anatomical standpoint. 1. 1. For practical purpose the different degrees of coma were subdivided using as parameters signs and symptoms commonly found in comatose patients, as follows: 1. (a) impairment of consciousness (C 1): 2 cases; 2. (b) moderate coma (C 2): 14 cases; 3. (c) deep coma (C 3): 9 cases. 1. 2. The type of EEG activity found was grouped under the following three headings: 1. (a) generalized EEG changes: 15 cases; 2. (b) unilateral EEG changes: 7 cases; 3. (c) focal EEG changes: 3 cases. 1. 3. The site of cerebral lesion was reconstructed on the basis of macro and microscopic sections. Electroclinical results show that a generalized slow organized activity is not necessarily the bioelectric expression of the majority of comatose patients. No definite relationships are found between degree of coma and type of electroencephalographic changes. Moreover the possibility of eliciting a bioelectric response to stimuli does not appear to be related to the depth of coma. Some interpretational problems posed by the EEG findings are discussed.

Liposome-entrapped GABA modifies behavioral and electrographic changes of penicillin-induced epileptic activity.

We studied Sprague-Dawley rats with spike activity and myoclonus after intraperitoneal injections of penicillin. Twenty minutes after penicillin injection, one group received a random crossover treatment by intraperitoneal GABA (gamma-aminobutyric acid) or liposome-entrapped GABA (LEG) or phosphatidylserine alone. The other group received GABA, LEG, or phosphatidylserine followed 15 minutes later by the injection of penicillin. LEG decreased or prevented the epileptic activity, whereas no significant changes were seen with either GABA or phosphatidylserine given alone. LEG may enhance penetration of GABA across the blood-brain barrier because of the carrier action of the liposomes.