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The concept of vascular dementia greatly evolved since Hachinski's description of multi-infarct dementia. Vascular dementias are reviewed with emphasis on current diagnostic criteria, elusive natural history, neuroradiological aspects, difficult epidemiological features and intriguing links with Alzheimer's disease. The recent proposed shift from vascular dementias to a broader definition of "vascular cognitive disorders", including non demented subjects with "vascular cognitive impairment", is described, followed by a brief review of current treatments.

Unlabelled: MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the standard imaging technique to assess the individual brain pathophysiological status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than DWI abnormality is thought to reflect the presence of tissue at-risk of infarction, i.e., penumbra. However, there has been no detailed study of the quantitative relationships between perfusion and diffusion changes in stroke patients. According to the experimental concept of penumbra, the ADC would be expected to remain unchanged despite decreasing perfusion until a critical threshold is reached. We have tested this hypothesis directly in man., Methods: DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs were positioned within the ADC lesion (D), the mismatch area (M), and the normal appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected ratios for ADC and rCBF were computed for each ROI., Results: The mean (+/-1 SD) ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N, respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and 0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A threshold for decline in ADC was apparent around 0.50 rCBF ratio., Comment: These results directly document in man that the ADC declines only after hypoperfusion has reached a certain degree (about 50%), consistent with the concept of the ischaemic penumbra.

When combined with cognitive investigations, functional neuroimaging methods such as positron emission tomography allow to depict the neural substrates that underlie the neuropsychological alterations in Alzheimer's disease. Capitalising on the variance in both cognitive performances and resting cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's disease, it is possible to correlate these two quantitative variables on a pixel-by-pixel basis and to generate maps showing the significant correlations in stereotaxic space. Some examples using this approach in the domain of memory disorders are presented in this brief review. We notably show that the localisation of the significant correlations differs from one memory system to another, as evaluated by clinical memory tasks. This approach also unravels the compensatory mechanisms that take place with evolution of the disease. Over and above its interest in clinical neuropsychology, this method constitutes a new source of inferences complementary to the classic activation paradigm in normal subjects, as the latter identifies the cerebral structures that are involved with, but not necessarily indispensable for, the normal execution of the task. This approach highlights the interest of combining functional neuroimaging and neuropsychology to better understand the neural substrates of cognitive deficits in both patients with memory disorders and elderly normal subjects.

Over the last 20 years, functional neuroimaging has led to major advances in the understanding of the pathophysiology of migraine. The migraine aura is characterized by the occurrence of an hypoperfusion of moderate intensity which is peculiar by its initial appearance in the posterior cortex and its anterior spread at a speed of about 2 to 3mm per minute, congruent with the migrainous march of neurologic deficit and reminiscent of the phenomenon of cortical spreading depression described in the laboratory animal after various neuronal aggressions. The hypoperfusion is followed by a phase of long-lasting hyperperfusion temporally dissociated from the headache, which seems rather to result from vasodilatation and inflammation of the extra-cerebral large vessels. Although this sequence of hypoperfusion followed by hyperperfusion would be consistent with an ischemic process, there is presently no formal argument in favour of such a process being operational in migraine aura. It is however possible that migrainous subjects are genetically susceptible to the development of some unknown process at the borderline between spreading depression and classic ischemia. In migraine without aura, the data indicate only rare and mild changes in brain perfusion, although there also exist isolated observations of pauci-symptomatic spreading bilateral hypoperfusion. Physiologic imaging has also documented the occurrence during migraine without aura of a dorsal mesencephalic activation in the vicinity of the raphé and the locus coeruleus, independent of the pain itself and which might represent the long sought-after "migraine generator". It remains unknown if this phenomenon is also present in migraine with aura. The main prevalent hypotheses attempting a synthesis of all the available data are briefly presented in the conclusion.

Physiologic imaging has recently allowed major new insights into the pathophysiology of acute ischemic stroke in man. The main observation concerns the major heterogeneity in pathophysiological patterns, with three situations being encountered: 1) cortical ischemic penumbra persisting up till 16 hrs post onset, which would represent an ideal therapeutic target; 2) early spontaneous reperfusion, predictive of favourable clinical and tissular outcome, and a priori requiring no specific therapy; and 3) early extensive necrosis, predictive of malignant hemispheric infarction. Physiologic imaging should soon become a fundamental tool in the evaluation of the individual pathophysiologic situation before a therapeutic decision about entry into trials is made.

In dementias and memory impairments of neurodegenerative origin, imaging of brain metabolism and perfusion by means of positron or single-photon emission tomography or functional MRI has utility in the following domains: 1) pathophysiology, by revealing the topography and severity of synaptic damage even at the earliest stages of the disease, at a time when structural imaging is of little or no help; 2) diagnosis, by showing profiles of abnormalities characteristic to each disorder, even though such profiles are neither specific to, nor constantly present in each disorder; 3) pharmacology, by providing a surrogate marker to evaluate objectively the effect of the drug being tested; and 4) neuropsychology, by mapping both the brain structures that underlie each subtype of memory impairment, and the reorganisation of large-scale networks that subserve task performance despite established synaptic lesions.

The investigation by means of functional neuroimaging techniques, notably positron emission tomography, of the neural networks involved in perceptual processes is presently carried out according to two different though complementary approaches. In one of them, the relationships between impairments in perceptual processes and alterations in resting brain metabolism are studied in brain-damaged subjects, according to the classic paradigm of neuropsychology, but here the metabolic alterations reflect the functional disruption of neural networks directly or indirectly affected by the focal brain lesion. In the other approach, one records the changes in local synaptic activity in response to a given stimulation or task, as compared to a reference condition; thus far this second approach has been mainly applied to the normal human subject. Though different, both approaches highlight the neural networks involved in a given perceptual or cognitive task, which appear as a set of brain areas more extensive than that revealed by classic neuropsychology as necessary to perform the task. PET activation studies in the healthy subject have allowed to investigate, within each domain of perception, the successive "bottom-up" steps of information processing, from the most elementary ones carried out passively, to the most complex ones involving e.g., the semantic representations. The attentional aspects of perception have also been extensively investigated, notably selective "top-down" attention (which modulates the response of those brain areas that process the given perceptual attribute), sustained vigilance (which activates a parieto-prefrontal network in the non-dominant hemisphere), and mental imagery (which activates in a "top-down" fashion the entire perceptual network, including the primary cortices). The wide-scale application of this approach to brain-damaged subjects will seemingly soon provide important clues regarding the neural mechanisms of impaired perception and recovery therefrom.

A 49-year old man without relevant prior neurological disorder but with overweight, dyslipidaemia and mild glucose dysregulation, noticed on awakening a spontaneous, left-sided and painless numb chin, attributed to isolated mental neuropathy, which regressed entirely within a few weeks. The clinical condition was stable at 1-year follow-up. Ancillary investigations (including electromyography) did not disclose any cause to this episode, notably there was no underlying malignancy or systemic disease. A thorough literature review revealed another similar case which too remained unexplained. The hypothesis of a microvascular neuropathy in relation to vascular risk factors is cautiously raised; such a mechanism has been inferred previously in exceptional cases of regressive mental neuropathy in the context of sickle-cell crisis or systemic vasculitis. Thus, at variance with classical notions, the outlook of the numb chin syndrome is occasionally benign.

A 72 year-old right handed woman had a right sided anterior choroidal artery infarction. She presented the triad of hemiplegia, hemianaesthesia, and homonymous hemianopsia, as well as complete non-determinant hemisphere syndrome that combined: disorientation for place and time, anosognosia, hemiasomatognosia, left spatial neglect, constructional apraxia and spatial fabulation concerning both the present time and the weeks that preceded the vascular event. Language and verbal memory were normal. Spatial memory could not be studied because of the severity of the neglect. The clinical course was poor: when tested one and a half year post-onset, the hemiplegia, the hemianaesthesia, and the hemianopsia as well as left spatial neglect remained severe. Vestibular caloric stimulation, carried out with left ear cold water irrigation, resulted in brief but clear-cut alleviation of the spatial neglect. An MRI with both axial and coronal slices showed a right-sided infarct affecting the whole posterior limb of the internal capsule including the genu, the posterior part of the globus pallidus, the anterior third of the cerebral peduncle and the amygdala but sparing the thalamus and the corona radiata. This crescent-shaped lesion transected entirely the thalamo-cortical connection fibers which resulted in a "thalamic exclusion". The measurement of brain glucose utilisation with (18F)-Fluoro-2-Deoxy-D-Glucose and positron emission tomography performed in the chronic phase (3 months post-onset) showed an exceptionally severe and widespread hypometabolism of the right hemisphere, relative to the left hemisphere, which correlated with both the unusual, severe and protracted non-dominant hemisphere syndrome. All the brain regions on the right side were hypometabolic relative to the left including the temporal region (mostly medial temporal), the left cerebellar lobe, the frontal lobe (mostly prefrontal region), the occipital region and the thalamus. The hypometabolism of the basal ganglia, the sensorimotor area and the parietal cortex was less severe. This most uncommon clinical-metabolic presentation presumably reflects a global thalamo-cortical disconnection inducing a diffuse dysfunction of the whole hemisphere.

This brief overview summarises the literature regarding the effects of lesions of the basal ganglia (BG) on brain metabolism-an index of integrated synaptic activity. Interest in this field is because to show such effects may reveal the implication of neuron networks, damaged at the level of the BG, in the neuropsychological and behavioural expression of BG lesions. As an illustration of this, a parallel is drawn between the loss of psychic self-activation (also named "psychic akinesia" or "athymhormia") that follows bilateral lesions at variable sites of the prefrontal-striatal-pallidal-thalamic loop on one hand, and the mild prefrontal hypometabolism consistently observed in such cases. This paper also reviews the changes in brain metabolism found in progressive supranuclear palsy, Huntington's disease, Parkinson's disease, Wilson's disease and striato-nigral degeneration.

Immediately following a scream of fear, a sixty-year old woman complained of severe bilateral headache which relapsed several times over the following month during exercise. There was no history of sympathomimetic drug intake. The work-up was normal save for minimal subarachnoid bleeding and the angiogram showed a disseminated "sausage-string" appearance over all cerebral arterial territories, without aneurysm. The unusual triggering event in this case and the subsequent recurrence of headache in relation to exercise lead us to discuss possible links between the clinical entity of "Isolated benign cerebral angiopathy" and exertional headache.

Four right-handed patients (69, 58 and 68 year-old men; 85 year-old woman) complained of motor difficulties with their left hand (3 cases), or both hands predominant on the left side (1 case). Continuous (1 case) or intermittent (2 cases) myoclonus was noted in the left arm. These disorders gradually progressed for 3 to 10 years. Clinical examination disclosed absence of motor, sensory (except in 1 case), or visual deficit. There were no cerebellar signs, no parkinsonian features (except for mild rigidity in 1 case), and no oculomotor abnormality. On the other hand, neuropsychological examination showed evidence of visuo-constructive apraxia in all cases, dressing apraxia in 3/4 cases and writing impairment in 3/4 cases. There was no amnesia, no aphasia and no intellectual impairment. MRI showed atrophy of the parietal areas, predominant on the right side. A positron emission tomography study was performed in all cases, and twice in 1 case. Cortical energy metabolism was measured using either 18 F-fluorodeoxyglucose or 15 O-Oxygen, to calculate the cerebral metabolic rate of glucose (CMRglu) or oxygen (CMRO2) respectively. Cortical metabolism was significantly decreased in the whole cortex of the right hemisphere in 3 cases, and was also reduced in the cortex of the left hemisphere, significantly in 1/3 studied planes. Moreover, regional metabolic indices (CMRO2 or CMRglu/cortex) showed a significant decrease in both the right and left posterior associative areas (temporo-parieto-occipital cortex), predominantly marked on the right side in 3 cases, indicating bilateral cortical dysfunction. At follow-up, one patient became progressively demented, another had visuo-spatial disorders indicating a lesion of both parietal areas. The relationships of our cases with the slowly progressive apraxia syndrome and with corticobasal degeneration are discussed.

Transverse axial tomographic imaging of regional cerebral blood flow (rCBF) and regional oxygen extraction fraction (rOEF) were obtained in 13 patients hospitalizedfor ischemic strokes (eleven middle cerebral artery territory infarcts, one capsular or pontine lacune, one transient hemispheric attack) by continuous inhalation of 15O2 and C15O2 to equilibrium and exclusive detection of the gamma rays emitted in coincidence by means of a tomograph for positron emitting agents. In the transient ischemic attack and in the case of lacune the rCBF and the rOEF images were found to be normal, and they were abnormal in all cases of middle cerebral artery territory infarcts. In recent infarcts, rOEF was always strikingly decreased in the clinically suspected area, whilst the rCBF was either decreased, normal or increased. In infarcts older than 30 days rCBF was always clearly decreased over the clinically suspected area whilst rOEF was in most cases normal or only slightly decreased. These results are briefly discussed. Some practical and theoretical limitations of this method are mentioned. The potential of the present technique appears great however, since it is possible to simultaneously visualize in tomographic fashion the blood flow and the oxygen metabolism in areas of the brain that are of small volume, and however deep they are. A quantification of these parameters is presently under investigation, as well as the verification of the theoretical model on which such method is based. The non-invasiveness of the present method, the feasibility of repeating it at regular intervals of time, and the possibility of measuring the immediate effects of a given therapeutic mode on the regional metabolism of brain all constitute further advantages whose action apply preeminently in the field of the cerebral ischemic diseases.

A 59-year-old hypertensive patient presented with dysesthesias and a pure sensory deficit involving face, arm and leg on the left side of the body. CT scan and MRI showed a small hematoma in the posterior and lateral part of the right thalamus.

The visualisation of the lower urinary tract by the mean of a fiberscope makes an advance when compared to rigid endoscopy mainly in male patient. Technical features of the fiberscopes suitable for urology thus basic technique of the examination are described. Main advantages are painfree and total visual scanning of the mucosa. Disadvantages are very low.

A young man with a left hemifacial hemangioma had during a six months period about forty left hemispheric neurologic attacks suggestive of classic migraine. The neurologic examination was normal during the attack-free period. The CT scan (fig. 1) and the M.R.I. study (fig. 2) only showed a moderate interhemispheric asymmetry. The left internal carotid angiogram showed subtle anomalies of the venous system (fig. 3). All the neurologic manifestations ceased as soon as therapy by aspirin was initiated. A Positron Emission Tomography (PET) study with the oxygen 15 continuous inhalation technique was performed 7 months after the last attack in order to measure the regional Cerebral Blood Flow (rCBF), Oxygen Extraction Fraction (rOEF) and Oxygen Consumption (rCMRO2). Striking, statistically significant, alterations were observed in the left temporo-parieto-occipital area (fig. 4) consisting of a "misery perfusion" syndrome (rCBF = 28-38 ml/100 g/mn; rOEF = 0.64-0.80), without alteration in the rCMRO2 (Table). A repeated PET study 12 months later was unchanged. The association of local chronic oligemia and ipsilateral facial hemangioma, ipsilateral cerebral hypotrophy and venous anomalies suggested the diagnosis of atypical leptomeningeal angiomatosis of the Sturge-Weber type. The importance and persistence of the hemodynamic alterations suggest that chronic oligemia and, hence, tissue hypoxia may participate in the pathogenesis of the migraine-like attacks. Moreover, local circulatory stasis with thrombotic events may be implicated, as suggested by the apparent efficacy of aspirin.

Cerebral Blood Flow (CBF), Oxygen Extraction Fraction, and Oxygen utilization (CMRO2) have been studied in 15 patients before and After Extra-Intracranial Arterial bypass (EIAB), using PET and 150 steady-State Inhalation technique. Fourteen patients had carotid artery obstructive lesions and the last one a middle cerebral artery occlusion. In the whole group of patients, both CBF and CMRO2 increased significantly on both cerebral hemispheres after the EIAB. This effect was more marked in patients with extensive occlusive disease of neck vessels. This metabolic improvement afforded by EIAB in our patients suggests that long-standing hemodynamic failure may induce a metabolic depression that's still potentially reversible by surgical revascularization. On the other hand, improvement of focal CBF abnormalities depends, in our patients, upon the preoperative coupling of CBF-CMRO2 (mainly misery perfusion syndrome) as reported earlier.

This review first brings justification to performing controlled therapeutic trials in migraine. It then describes the organisation of a prophylactic trial; the criteria for inclusion and exclusion, the various possible protocols, and the data analysis are discussed, while the many difficulties and pitfalls brought about by the natural characteristics of the disease are stressed. Some limitations inherent to prophylactic trials and to migraine when interpreting the results are emphasized. The findings of the prophylactic trials published to date are briefly summarized in three tables; the results indicate both the usefulness and the validity of this methodological approach in migraine. The main features and specific difficulties of the controlled trials of drugs the treatment of migraine attacks are briefly commented, and the literature review is broadly tabulated. Lastly, a brief account of the problems involved in controlled trials of non-chemical migraine therapy is given. Despite their numerous limitations, the controlled trials have considerably clarified the therapeutic approach of migraine.

The oxygen 15 non invasive continuous inhalation technique coupled with positron emission tomography (P.E.T.) allows the local study of cerebral blood flow and oxygen metabolism. Recent P.E.T. studies have demonstrated the frequent occurrence of widespread metabolic depression remote from the site of middle cerebral artery territory infarct per se, especially over the cortical mantle and thalamus ipsilaterally, and over the cerebellar hemisphere contralaterally. These phenomena have been taken as indicative of transneural depression (i.e. diaschisis). We thought it interesting to study the possible occurrence of such abnormalities in patients with lacunar syndromes. We have applied the (15)0 technique to six patients (2 with pure motor hemiplegia, 4 with ataxic hemiparesis) for whom no large causal ischemic lesion could be demonstrated on CT scans; in only one patient was a lacunar lesion, presumably responsible for the clinical deficit demonstrated. Compared to a set of 19 patients without brain disease, the semi-quantitative results (analyzed in terms of asymmetry indices between homologous brain regions) in our patients did not disclose any pathophysiologically significant abnormality. More specifically, no evidence of physiological dysfunction similar to that reported in internal carotid artery territory infarcts, was detected over the cerebral or cerebellar cortices. These findings are commented upon in view of the presumably small size and the uncertain topography of the causal lesion.

In an attempt to characterize in vivo the central serotonergic (5-HT2) receptors in humans with positron emission tomography (PET), we have used 11C-labeled-ketanserin, a seratonergic antagonist that has high affinity and selectivity for the 5-HT2 receptors in vitro. Earlier in vivo studies in rats had demonstrated a preferential accumulation of 3H-ketanserin in the frontal cortex relative to cerebellum, in accordance with known differences in density of 5-HT2 receptor in these two brain structures (5-HT2 receptors are dense in frontal cortex and sparse or absent in cerebellum). In rats, tracer accumulation in frontal cortex represented specific binding of 3H-ketanserin to 5-HT2 receptors in vivo as demonstrated by inhibition, saturation, and displacement studies. In 5 control subjects, we found a statistically significant retention of 11C-ketanserin in frontal cortex relative to cerebellum after intravenous injection of a tracer dose of the radioligand, suggesting specific in vivo binding of 11C-ketanserin to frontal cortex. To substantiate this hypothesis, we studied 4 subjects administered unlabeled chlorpromazine (CPZ) intramuscularly in therapeutic amounts (75 mg) two hours before the PET study. Pretreatment with CPZ decreased significantly the retention of 11C-ketanserin by the frontal cortex, indicating that almost total occupation of the ketanserin receptors by CPZ had been achieved prior to the injection of the radioligand. Despite these positive results, both the duration and the magnitude of tracer retention by frontal cortex in control subjects were much smaller than was reported in rats, presumably indicating lower specific binding, higher nonspecific binding, and faster drug metabolism in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Using positron emission tomography and the 15O continuous inhalation technique, we have measured the regional cerebral blood flow (rCBF) oxygen extraction fraction (rOEF) and oxygen consumption (rCMRO2) of non-infarcted tissue in six patients with either tight stenosis (N = 3) or occlusion (N = 3) of the trunk of the middle cerebral artery (MCA); these arterial lesions were shown to be persistent on late and/or repeated angiograms. The patients were studied 1 to 6 months after their last cerebral ischemic event. The data were analyzed in 4 cm2 regions of interest (fig. 1) and were compared to age-matched control values. Regional right/left ratios were tested for significance individually by comparison to 95 p. 100 confidence limits found in control subjects. We found a significant reduction in mean rCBF in the affected MCA territory; concomitantly, there was a lesser decrease in rCMRO2 significant only in the peri-sylvian area; this was associated with a moderate but significant increase in rOEF in the same areas (Table II, fig. 2 and 3). Individually, the reduction in rCBF and the increased rOEF were significant in 5/6 and 2/6 patients, respectively (Table III). These data indicate that rCBF is decreased distal to persistent hemodynamic MCA obstruction in most patients. This hypoperfusion appears due in part to a mild degree of cerebral ischemia (as demonstrated by the occurrence of "misery perfusion"), indicating inadequate perfusion pressure distal to the MCA obstruction. This was associated with a metabolic depression of the cortex possibly resulting from either neuronal loss, or deactivation (diaschisis), or long-standing hemodynamic local failure or any combination of the three.(ABSTRACT TRUNCATED AT 250 WORDS)

We used positron emission tomography to study the effects of unilateral vascular thalamic lesions on cortical oxygen or glucose utilisation in 10 patients. There was a significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting diffusely the whole cortical mantle. The only patient spared was free of neuropsychological deficit at time of PET study. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at follow-up PET study, together with improved neuropsychological function. When plotted altogether, the 14 studies showed a significant tendency for the hypometabolism to improve with time elapsed since clinical onset. On the whole, these data suggest that the ipsilateral cortical hypometabolism reflects an essentially functional alteration an not only a degenerating process. This most likely indicates a cortical deafferentation due to loss of non-specific thalamo-cortical connections, i.e. a phenomenon akin to "diaschisis". However, a causal relationship between cortical hypometabolism and neuropsychological deficit cannot be firmly established from the present data.

Another case of obsessive behaviour as the consequence of lentiform nuclei lesions is reported. All the aspects of an obsessive neurosis were present: irresistible compulsiveness, acute anxiety in case of non accomplishment, magic-like clues. The symptoms appeared after a carbon monoxide poisoning, in a 31-years-old woman who had previously a pathological personality, of the psychopathic type, but without obsessive features. The onset of compulsions was paralleled by frontal-like psychological changes, but there was no reduction of intellectual or mnesic functions. A previous depressive state continued after the poisoning, so that the patient did not show an empty mind as did the other patients; the loss of "self-psychic activation" was only partial. All these case-reports emphasize the fact that the neuropsychological testing must not be limited to the behaviour and must investigate the "mental content" as well. They also lead us to emphasize similitudes between psychic disorders related to lenticular lesions and those related to frontal lobe lesions, including obsessive-like activities. Such case-reports provide a model in which some components of the obsessive neurosis, hebephrenia and depression are the consequence of an identified brain damage. It can be suggested that the neural circuits involving frontal lobes and parts of the neostriatum and of the pallidum are implicated in the mechanisms of these three types of psychoses.

The case, including pathological description, of a 65 year old man is presented. Severe disturbances in respiratory rhythm and consciousness occurring during wakefulness and sleep, progressing by acute exacerbations, developed after the disease had been present for 4 years and resulted in death after three months. Small degenerative lesions of the pontine nucleus, the locus coerulus, the intermedio-lateral column and the substantia nigra were seen.