Prediction of malignant middle cerebral artery infarction by diffusion-weighted imaging.

BACKGROUND AND PURPOSE: This study was designed to analyze whether early diffusion-weighted imaging (DWI) provides reliable quantitative information for the prediction of stroke patients at risk of malignant brain infarct. METHODS: We selected 28 patients with a middle cerebral artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MRI angiography performed within 14 hours after onset (mean 6.5+/-3.5 hours, median 5.2 hours). Of these, 10 patients developed malignant MCA infarct, whereas 18 did not. For the 2 groups, we compared the National Institutes of Health Stroke Scale (NIHSS) score at admission, site of arterial occlusion, standardized visual analysis of DWI abnormalities, quantitative volume measurement of DWI abnormalities (volume(DWI)), and apparent diffusion coefficient values. Univariate and multivariate discriminant analysis was used to determine the most accurate predictors of malignant MCA infarct. RESULTS: Univariate analysis showed that an admission NIHSS score >20, total versus partial MCA infarct, and volume(DWI) >145 cm(3) were highly significant predictors of malignant infarct. The best predictor was volume(DWI) >145 cm(3), which achieved 100% sensitivity and 94% specificity. Prediction was further improved by bivariate models combining volume(DWI) and apparent diffusion coefficient measurements, which reached 100% sensitivity and specificity in this series of patients. CONCLUSIONS: Quantitative measurement of infarct volume on DWI is an accurate method for the prediction of malignant MCA infarct in patients with persistent arterial occlusion imaged within 14 hours of onset. This may be of importance for early management of severe stroke patients.

Myelin basic protein in CSF and blood. Relationship between its presence and the occurrence of a destructive process in the brains of encephalitic patients.

Serum and CSF levels of myelin basic protein (MBP) were measured in 50 patients with encephalitis of various origins and severity. In nearly 50%, the CSF samples were found to display immunoreactivity of MBP. Positivity was found to be correlated with the severity of the clinical signs. More precisely, it corresponded to cases with suspected extensive brain destruction. No relationship could be observed with the cause of disease. Positive tests of sera were infrequent, even from patients whose CSF was rich in MBP. Longitudinal studies performed on 20 patients who were serially investigated during periods ranging from three weeks to 18 months demonstrated that after an attack, MBP liberation into the CSF persists for one to three weeks. The MBP assay should serve as an index for destruction of nervous tissue.

Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions.

OBJECTIVE/BACKGROUND: Case studies suggest a dissociation between cognitive functions that have been impaired after damage to the dorsolateral prefrontal cortex and social skills disturbed when the ventromedial prefrontal areas are affected. Because this dissociation had not been confirmed in a clinical setting, clinicometabolic correlations were sought in 13 patients with various lesions of the prefrontal cortex. DESIGN/METHODS: The clinical assessment included extensive testing of executive functions and evaluation of behavioral abnormalities based on an informant questionnaire. Regional cerebral glucose metabolism (rCMRGlu) was measured with [l8F] fluorodeoxyglucose ([18F] FDG) and 31-slide high-resolution PET. RESULTS: Executive-function test performance was significantly correlated with rCMRGlu in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9, 45, 46, and 47) and anterior cingulate cortex (Brodmann's areas 24 and 32). Behavioral scores were significantly correlated with rCMRGlu in the frontopolar (Brodmann's area 10) and orbitofrontal cortex (Brodmann's areas 11, 12, 13, and 14). CONCLUSION: These results show that impaired executive functions and serial skill deficits are associated with distinct metabolic patterns in patients with frontal lobe pathology. In agreement with activation studies in normal subjects, our data suggest the existence of a modular organization of the frontal cortex in humans, as previously reported in nonhuman primates.

The phenotype of "pure" autosomal dominant spastic paraplegia.

We studied 23 families with "pure" autosomal dominant spastic paraplegia. Examination of 142 at-risk individuals allowed identification of 70 patients, including 12 who were clinically affected but unaware of symptoms. The frequency of lower limb muscle weakness, decreased vibration sense, hyperreflexia in the upper limbs, and sphincter disturbances increased with the disease duration. The distribution of age at onset was unimodal, with a mean onset of 29 years (range, 1 to 68). The clinical manifestations of "early-onset" (< 29 years) and "late-onset" (> 29 years) patients were not significantly different. Age at onset varied as much within families as among families; anticipation and imprinting did not occur. No clinical criteria allowed differentiation among the families studied. Only linkage studies can provide accurate classification of this disease.

Fatal familial insomnia: clinical and pathologic study of five new cases.

In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

Recovery from nonfluent aphasia after melodic intonation therapy: a PET study.

We examined mechanisms of recovery from aphasia in seven nonfluent aphasic patients, who were successfully treated with melodic intonation therapy (MIT) after a lengthy absence of spontaneous recovery. We measured changes in relative cerebral blood flow (CBF) with positron emission tomography (PET) during hearing and repetition of simple words, and during repetition of MIT-loaded words. Without MIT, language tasks abnormally activated right hemisphere regions, homotopic to those activated in the normal subject, and deactivated left hemisphere language zones. In contrast, repeating words with MIT reactivated Broca's area and the left prefrontal cortex, while deactivating the counterpart of Wernicke's area in the right hemisphere. The recovery process induced by MIT in these patients probably coincides with this reactivation of left prefrontal structures. In contrast, the right hemisphere regions abnormally activated during simple language tasks seem to be associated with the initial persistence of the aphasia. This study supports the idea that abnormal activation patterns in the lesioned brain are not necessarily related to the recovery process.

Somatosensory cortical activations are suppressed in patients with tactile extinction: a PET study.

OBJECTIVE: To investigate whether tactile extinction alters the cortical somatosensory activations induced by hand vibration. BACKGROUND: Tactile extinction occurs mainly after right-brain lesions and consists of the inability to perceive a contralesional cutaneous stimulation when a similar stimulus is applied to the mirror region of the ipsilesional hemibody. The pathophysiology of tactile extinction is poorly understood, but it is considered to be a deficit of selective attention of somatosensory stimuli. Although other theories have been proposed, our understanding of the pathophysiology of tactile extinction may benefit from functional imaging studies. METHODS: We selected three patients with pure tactile extinction and a mainly subcortical right-brain lesion that spared the primary sensorimotor cortex (SM1). We used PET to investigate the responses to unilateral and bilateral hand vibration in SM1 and the secondary somatosensory cortical area (SII). RESULTS: During bilateral hand vibration, activation was normal in the left SM1, suppressed in the right SM1, and markedly decreased in both SII, which was consistent with the extinction of the left-hand stimulus. During unilateral left-hand vibration, the activation of the right SM1 was still markedly impaired, but the activation of both SII was normal. CONCLUSIONS: We found marked changes in the activation of cortical somatosensory areas induced by hand vibration in patients with tactile extinction. The role of selective attention in cortical activation is also examined.

Post-stroke changes in cortical 5-HT2 serotonergic receptors.

UNLABELLED: Fluorine-18-setoperone PET imaging was used to investigate serotonergic 5-HT2-specific binding in unlesioned cerebral cortex in stroke patients. METHODS: Seventeen stroke patients (mean age 50 +/- 31 yr) with right (n = 9) or left (n = 8) chronic stroke (middle or anterior cerebral artery territory) underwent [18F]setoperone PET and MR imaging. The distribution volume of the 5-HT2-specific binding at equilibrium (DVSe) was determined in the unlesioned cortical regions. The results were compared with those obtained in 14 age-matched controls. In addition, we investigated the effect of the side of the stroke, lesion volume and its localization. RESULTS: After removing the age effect by covariance analysis, we found a significant DVSe decrease in the temporal (p < 0.05) and frontal (p < 0.05) unlesioned cortices ipsilateral to the stroke. The changes were similar in patients with left and right stroke and did not correlate with the volume of the stroke. However, the localization of the stroke affected the topography of DVSe abnormalities. When the lesion did not extend more medially than the internal capsule, DVSe was significantly reduced in the temporal lobe (-30%, p < 0.05) but not in the frontal lobe (-21%, p = ns). Conversely, when the lesion extended subcortically in the anteromedial region, close to the midline, DVSe was reduced in both temporal (-40%, p < 0.05) and frontal (- 49%, p < 0.05) lobes. CONCLUSION: This study confirms that stroke may alter 5-HT2 receptors in large unlesioned cortical areas and that the changes depend on the subcortical extent of the lesion.

Cerebellar dysfunctions of temporal processing in the seconds range in humans.

The roles of the basal ganglia and cerebellum in timing remain subject to debate. It has been suggested that temporal range may dissociate them, since cerebellar research has focused on intervals of < 1 s, compared with many seconds used in much basal ganglia research. Here we show increased but scalar variability of time estimates in patients with focal lesions of the lateral cerebellar cortex and nuclei when trained to remember durations in the seconds range, compared with patients with lesions of the mesial cerebellum and vermis. This distortion is discussed on the basis of previously reported cerebellar deficits in different time ranges and contrasted to distortions occurring in patients with basal ganglia lesions performing similar tasks over similar time ranges.

Aphasia and infarction of the posterior cerebral artery territory.

Spoken language disorders are rarely mentioned in superficial infarction of the posterior cerebral (PCA) territory. Two clinical types have been reported: transcortical sensory and amnesic aphasia. Between 1979 and 1990, we studied retrospectively 76 patients suffering from an occipitotemporal infarction located in the superficial territory of the posterior cerebral artery, all well documented by CT. Aphasia was one of the first and prominent signs in 18 cases. Middle cerebral artery concomitant infarction could have been the cause of language impairment in 10. In 8 patients aphasia was only explained by a PCA territory infarct. Three patients showed features of transcortical sensory aphasia. CT localization showed internal lobe and thalamic involvement of the dominant hemisphere. Five patients exhibited word finding impairment with various degrees of amnestic syndrome. The dominant internal temporal lobe was always affected. Dominant thalamus involvement was found in one case only. Some correlations between clinical features and anatomical support (vascular supply and anatomical structure) might be suggested in our 8 cases of aphasic disorders due to PCA infarcts. They are discussed and compared with data in the literature.

Absence of aluminium in Alzheimer's disease brain tissue: electron microprobe and ion microprobe studies.

Brain tissue from the frontal cortex and hippocampal formation, taken at autopsy or biopsy from 7 patients with Alzheimer's disease, was studied by two methods of microanalysis. One case of Down's syndrome was also studied. Electron probe microanalysis of the frontal cortex and Ammon's horn of the hippocampus showed no aluminium in the various cell organelles, especially in the lysosomes, although some aluminium was found in a few contaminating dusts. Ion microscopy, a method of extremely high sensitivity, also showed the absence of an aluminium signal.

False-negative diffusion-weighted MR findings in acute ischemic stroke.

BACKGROUND AND PURPOSE: Lesions associated with acute stroke are often missed by diffusion-weighted imaging (DWI), suggesting that the sensitivity of this technique for detecting acute ischemic stroke may not be as high as initially thought. Our aim was to estimate the rate of false-negative DWI studies in patients with persistent neurologic deficit due to an ischemic stroke and to identify which stroke lesions are most likely to be missed by DWI. METHODS: We reviewed MR images obtained within 48 hours after stroke onset in 139 patients admitted for symptoms consistent with ischemic stroke in whom the deficit lasted more than 24 hours. Cases of negative initial DWI findings with an ischemic lesion visible on follow-up MR studies and a final diagnosis of arterial ischemic stroke were analyzed in terms of delay between onset of symptoms and initial DWI (MR latency), size and vascular distribution of the lesions, and relationship to findings in patients with positive initial DWI results. RESULTS: We found eight cases (5.8%) of false-negative initial DWI studies, of which four were positive on initial fluid-attenuated inversion recovery (FLAIR) imaging. Follow-up FLAIR/DWI showed a hyperintensity matching clinical presentation in all eight patients. The mean size of the lesion was 0.19 +/- 0.16 cm3. False-negative studies occurred more often in cases of stroke in the posterior (19%) than in the anterior (2%) circulation or when DWI was obtained within 24 hours after symptom onset. Of the six false-negative vertebrobasilar stroke lesions, five were located in the brain stem. In all, 31% of patients with vertebrobasilar ischemic stroke had a false-negative initial DWI study during the first 24 hours. CONCLUSION: A false-negative DWI study is not uncommon during the first 24 hours of ischemic stroke. Vertebrobasilar stroke should therefore not be ruled out on the basis of early negative DWI, especially when symptoms persist and are suggestive of this diagnosis.

Diffusion-weighted imaging patterns of brain damage associated with cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Apart from cases studies, little is known regarding diffusion-weighted imaging of brain lesions associated with human cerebral venous thrombosis (CVT). Our aim was to describe the initial diffusion-weighted imaging patterns observed in brain areas with MR signal changes associated with CVT and to compare them with those of follow-up imaging. METHODS: The cases of nine patients with brain lesions associated with CVT who underwent CT and diffusion-weighted imaging 3 hours to 4 days after sudden neurologic onset were retrospectively reviewed. The apparent diffusion coefficient (ADC) in abnormal brain was compared with that of contralateral normal regions using z score analysis. MR images obtained during 3 to 6 months of follow-up were available for seven patients. RESULTS: All patients had nonhemorrhagic T2-hyperintense brain regions. These were associated with partially hemorrhagic areas on the CT scans of four patients. In nonhemorrhagic edematous areas, ADC was heterogeneous (coexistence of increased, normal, or decreased ADC) in five patients and homogeneous in four. In the latter four patients, ADC values were within normal range in three, whereas a large homogeneous hyperintensity with decreased ADC values (0.3-0.4 10(-3)mm2/s, <-3 z scores) was observed in one. When available, follow-up images always showed hemorrhagic sequelae in initially hemorrhagic areas. Nonhemorrhagic edematous areas with initially increased ADC values returned to normal. Initially normal or decreased ADC values were predictive of reversibility, although imaging sequelae were rarely observed. CONCLUSION: The diffusion-weighted imaging/ADC pattern of venous stroke is more heterogeneous than previously thought. Large brain regions of reduced ADC values that are not predictive of ultimate infarction in cases of CVT can be observed.

Percutaneous transluminal angioplasty and stenting of the proximal vertebral artery for symptomatic stenosis.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty (PTA) for significant stenosis involving the origin of the vertebral artery is now a well established treatment for selected patients when posterior cerebral arterial circulation is compromised. Arterial spasm, dissection, and restenosis may occur in some instances, with subsequent hemodynamic compromise. To prevent these potential complications, we combined PTA of the vertebral artery with primary stenting, using coronary stents, in seven patients. We herein present our short- and intermediate-term results. METHODS: A total of seven lesions affecting the origin of the vertebral artery were treated by primary trans-stenotic coronary stent placement. All patients were symptomatic, fulfilling the general criteria for vertebral artery angioplasty. Patients were followed for up to 36 months after treatment. RESULTS: All seven lesions were successfully dilated. Residual stenosis was never greater than 20% in diameter. No perioperative complications occurred. Clinical follow-up showed immediate resolution or improvement of symptoms in all patients. One patient's condition deteriorated 15 months after stent placement because of atheromatous stenosis of the prevertebral segment in the ipsilateral subclavian artery. CONCLUSION: Stent placement to treat significant stenosis involving the origin of the vertebral artery is safe and effective for alleviating symptoms and improving blood flow to the posterior cerebral circulation. Coronary stent design seems to be particularly well suited to cover atherosclerotic lesions of the origin of the vertebral artery. The stent mesh probably prevents elastic recoil and early restenosis after PTA, as it does in coronary arteries.

The neuropathologic diagnostic criteria of frontal lobe dementia revisited. A study of ten consecutive cases.

Ten successive cases from the Neuropathology Laboratory of La Salpêtrière Hospital in Paris, were selected on the presence of: dementia and prominent symptoms and signs of the frontal type; a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions. We propose the following steps to diagnose the degenerative dementia associated with symptoms and signs of the frontal type: 1. If there is severe frontotemporal atrophy, severe neuronal loss and astrogliosis, many ballooned neurons and characteristic inclusions that are both tau and ubiquitin positive, the diagnosis is Pick disease. 2. If signs of motor involvement (sometimes unnoticed by the clinician) are present with mild cortical atrophy and mild spongiosis of layers II-III, the diagnosis of frontal lobe degeneration associated with motor neuron disease is warranted. Ubiquitin positive inclusions are useful, but non specific, markers. 3. When there are neither Pick inclusions nor motor neuron disease, the diagnosis may be frontal lobe atrophy lacking distinctive histology.

[Verbal fluency and EEG coherence in Alzheimer's disease]. / Fluidité verbale et cohérence EEG dans la maladie d'Alzheimer.

EEG coherence of 16 derivations and a verbal fluency test were evaluated on 25 ambulatory patients suffering from Alzheimer's disease (age: 74 +/- 5.7). The aim of the study was to analyze coherence rate variations from different cortical areas in relation to the performance in the test. Coherence rates of each derivation with the other ones were calculated for four frequency bands from 0.5 to 13.5 Hz. Arithmetic averages of these rates were then calculated to obtain scalp averaged coherence rates. The patients were submitted to a verbal fluency test and divided into two groups according to their test score as compared to normative data: impaired (n = 10) and not impaired (n = 15). Results showed that averaged coherence rates of theta and alpha 1 frequency bands were significantly depressed in the impaired group in comparison with those of the not impaired group. Two cortical areas were concerned with this difference, the left temporo-occipital and frontal zones, in an independent way for the same subject. Moreover, we observed that the patients who where impaired in the verbal fluency test, also presented a significantly greater ancientness of the clinical symptoms as compared to the not impaired patients.

[Unilateral benign episodic mydriasis]. / Mydriase épisodique unilatérale bénigne.

Ophthalmoplegic migraine is a rare phenomenon. In this setting, extrinsic as well as intrinsic fibers of the third nerve are involved. We report 2 cases of isolated, unilateral, remitting, mydriasis and describe 23 other cases already published. CT scan, MRI and angiogram were always normal when performed. The pathophysiology of this syndrome is probably related to a migrainous manifestation.

[Bismuth myoclonic encephalopathies. Their course and lasting or definitive late complications]. / Encéphalopathies myocloniques bismuthiques. Formes évolutives, complications tardives durables ou définitives. A propos de 41 cas.

Acute myoclonic encephalopathy related to the ingestion of bismuth salts has been known for 3 years and would appear to be reversible. Of a total of 41 cases, 32 were observed for an average of more than a year. Alongside the commoner benign forms, there coexist severe forms, sometimes fatal, prolonged forms and complicated forms. Permanent deterioration, affecting memory above all, tremor, marked insomnia, headache and disturbed gait are amongst the most durable complications, sometimes definitive, whilst in four cases osteo-arthropathy of the shoulders was associated with permanent invalidism.

[Tomodensitometric aspects of 3 cases of acute bismuth encephalopathy (author's transl)]. / Aspects tomodensitométriques de trois observations d'encéphalopathies bismuthiques aigues.

A study of 3 cases of acute bismuth encephalopathy by C. T. scanner revealed indisputable evidence of abnormal hyperdensity in certain brain regions. These hyperdensities, or rather hyperattenuations, are very typical in case no. 1, where the central grey nuclei, especially the caudate nuclei and cerebral cortex, have an important hyperdence appearance. The images are heterogenous, sometimes granular, and are not modified by the injection of a contrast medium. There are also ventricular and cisternal dilatations which are even more remarkable when the age of the patients (less than 45 years) is considered. Cases Nos. 2 and 3 showed hyperdensity which was mainly in the cortical hemispheres. Blood bismuth levels vary according to the date of bismuth stoppage, lying between 850 and 1.350 microgram p. 1.000 ml. The pathogenesis of these tomodensitometric images are discussed as a function the of atomic number of bismuth metal and its unequal distribution in the cerebral parenchyma and the meninges.

[Amnestic syndromes and confabulation in infarction of the posterior cerebral artery area]. / Syndromes amnésiques et fabulations au cours d'infarctus du territoire de l'artère cérébrale postérieure.

The Posterior Cerebral Artery (PCA) supplies the greatest part of the limbic system. Several authors have reported amnestic syndromes in PCA infarcts. Amongst 76 patients with a CT proven PCA infarct, 21 suffered anterograde amnesia. Confabulations were associated in 5 cases. We studied CT scans according to previously reported templates in the 21 amnestic patients: all patients with confabulations had a paramedian or a tuberothalamic infarct associated with a cortical infarct within the superficial territory of the PCA. None of the 16 remainders had a thalamic lesion. These results emphasize the role of the thalamus especially of the dorsomedial nucleus in the pathogenesis of confabulation. The underlying mechanism could imply fronto-cingular deafferentation.