Search PubMed⌕ Search

Biomedical subjects

Julien Bogousslavsky

Publications and source records attributed to Julien Bogousslavsky.

At least 19 recordsLinked to original sources

A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia.

Neuronal death in cerebral ischemia is largely due to excitotoxic mechanisms, which are known to activate the c-Jun N-terminal kinase (JNK) pathway. We have evaluated the neuroprotective power of a cell-penetrating, protease-resistant peptide that blocks the access of JNK to many of its targets. We obtained strong protection in two models of middle cerebral artery occlusion (MCAO): transient occlusion in adult mice and permanent occlusion in 14-d-old rat pups. In the first model, intraventricular administration as late as 6 h after occlusion reduced the lesion volume by more than 90% for at least 14 d and prevented behavioral consequences. In the second model, systemic delivery reduced the lesion by 78% and 49% at 6 and 12 h after ischemia, respectively. Protection correlated with prevention of an increase in c-Jun activation and c-Fos transcription. In view of its potency and long therapeutic window, this protease-resistant peptide is a promising neuroprotective agent for stroke.

Adaptor Proteins, Signal Transducing↗

Central Horner's syndrome with contralateral ataxic hemiparesis: a diencephalic alternate syndrome.

OBJECTIVE: To assess whether thalamic strokes presenting with a central Horner's syndrome (HS) show specific clinicoanatomic patterns. METHODS: From the Lausanne Stroke Registry (period 1993 to spring 2002), the authors selected all patients with thalamic stroke presenting with ipsilateral HS. Patients with complete infarction of the posterior cerebral artery territory, with involvement of middle cerebral artery territory or bilateral lesions, were excluded. Lesions on brain MRI were correlated with standard neuroanatomic templates. RESULTS: Nine patients with thalamic infarction presenting with central HS were found; all showed contralateral ataxic hemiparesis (AH). Lesions involved the anterior or paramedian thalamus and extended to the hypothalamic or rostral paramedian mesencephalic area in all but one subject. Associated clinical signs included dysphasia (two patients), somnolence (six), vertical gaze paresis (two), asterixis (two), and hemihypesthesia (three). CONCLUSION: The alternate clinical pattern of central HS with contralateral AH is a stroke syndrome of the diencephalic-mesencephalic junction, resulting from the involvement of the common arterial supply to the paramedian/anterior thalamus, the posterior hypothalamus and the rostral paramedian midbrain.

Adult↗

Phenotypic expression of a Pro 87 to Leu mutation in the connexin 32 gene in a large Swiss family with Charcot-Marie-Tooth neuropathy.

BACKGROUND: The clinical manifestations of CMTX have been well described but the natural history has not yet been studied in detail. We studied phenotype variability in a family with a Pro 87 to Leu mutation of the connexin 32 (Cx32) gene. METHODS: A total of 32 family members, of which 19 patients were affected, underwent clinical, electrophysiological, and genetic studies. RESULTS: Onset was in the second decade. Clinical features were similar in both sexes when quantitative scores were compared, but more males had a steppage gait and skeletal deformities. All adult patients had a predominant involvement of the thenar muscles. The median values of nerve conduction velocities (NCVs) were not statistically different in men and in women. The correlation coefficients were low between motor NCVs within the same extremities, indicating nonuniform slowing between nerves, the ulnar nerve being the least affected. When disability was rated, a strong correlation was seen in male patients between severity of motor axonal loss and duration of the disease. The main pathological features were axonal loss, clusters of regenerating fibers and paranodal demyelination, the hallmark of a Schwann cell pathology. CONCLUSIONS: Our data support the hypothesis that clinical disability in CMTX is caused by loss of large myelinated axons in men. Furthermore, this study shows that the nerves are not uniformly affected in terms of axonal loss. Preventing axonal degeneration and promoting axonal regeneration in the most affected nerves might be the best therapeutic approaches to ameliorate disability in CMTX.

Adolescent↗

Acute stroke increases QT dispersion in patients without known cardiac diseases.

BACKGROUND: Electrocardiographic changes are well known to appear with acute cerebrovascular events. OBJECTIVE: To investigate if QT dispersion (QTd) is increased in patients who have an acute stroke and if this increase could be related to lesion extent and/or localization. DESIGN: The study group consisted of 36 patients who had an acute stroke and no history or signs of cardiovascular disease. An age-matched control group (n = 19) free of cardiovascular disease was also included. Simultaneous 12-lead electrocardiograms (ECGs) were recorded within the first 24 hours (24h-ECG) and after 72 hours (72h-ECG) from stroke onset. QT dispersion was assessed both manually and automatically with assessors blinded to the clinical data. RESULTS: QT dispersion, corrected QTd, and automated QTd were significantly increased in the 24h-ECG compared with the 72h-ECG (60 [range, 20-80] milliseconds vs 40 [range, 0-80] milliseconds, P<.005; mean [SD], 56 [19] vs 36 [21] milliseconds, P<.001; and 50 [range, 14-94] vs 34 [range, 0-84] milliseconds, P<.005, respectively). However, QTd in the 72h-ECG was similar to QTd in the control group. While in the 24h-ECG corrected QTd was significantly greater in patients with large infarcts and large hemorrhages (mean [SD], 70 [20] vs 51 [20] milliseconds, P<.05), in the 72h-ECG corrected QTd was greater in patients with right vs left-sided lesions (mean [SD], 39 [18] vs 24 [18] milliseconds, P<.05). CONCLUSIONS: QT dispersion is increased in the first 24 hours in patients with acute stroke and no cardiovascular disease compared with the control group. Although this finding seems to be related to the size of the lesion rather than to the localization or type of stroke, after 72 hours specific lesion localization could also influence the QTd.

Acute Disease↗

Acute infarction limited to the lenticular nucleus: clinical, etiologic, and topographic features.

BACKGROUND: Chronic diseases involving the putamen and globus pallidus induce parkinsonism and other movement disorders. Sensory and motor dysfunction from deep middle cerebral artery infarction is usually due to an involvement of the internal capsule. The clinical picture associated with isolated infarction of the lenticular nucleus is less well established. OBJECTIVE: To analyze clinical features, topographic correlations, and cause of purely lenticular ischemic infarction. PATIENTS AND METHODS: We reviewed 820 consecutive patients with deep hemispheral infarct included in the Lausanne Stroke Registry between 1986 and 1998 and selected those with isolated lenticular involvement on computed tomography or magnetic resonance imaging. RESULTS: Thirteen patients had pure lenticular infarction. All had faciobrachiocrural hemisyndrome, while none showed acute or delayed parkinsonism or abnormal movement. Nine patients had a lesion restricted to the putamen. Two of them had ataxic motor hemisyndrome and 7 had sensorimotor hemisyndrome (with ataxia in 4, left hemineglect in 1, and deep pain in the arm and leg in 1). Four patients had a lesion of putamen and globus pallidus externus. Three of them had motor hemisyndrome (with nonfluent aphasia in 2 and ataxia in 1) and 1 had ataxic sensorimotor hemisyndrome. All infarcts were in the territory of the medial perforating branches of the medial cerebral artery. Presumed cause of stroke was small-artery disease in 5, artery-to-artery embolism in 4, cardioembolism in 3 and undetermined in 1. CONCLUSIONS: Acute lenticular infarction induces mainly hemiparesis but no movement disorder. Associated sensory deficits, aphasia, and hemineglect underline clinically the function of the lenticular nucleus in connection with the prefrontal, temporal, and parietal cortices.

Acute Disease↗

Neurogenic pain and abnormal movements contralateral to an anterior parietal artery stroke.

BACKGROUND: Unlike delayed pain syndrome, acute central pain is a very rare symptom in acute stroke. In addition, the incidence of hemiballismus in acute cerebrovascular diseases is less than 1%. To our knowledge, the association of these 2 clinical conditions has not been previously described. PATIENT AND METHODS: After observing one patient with hemiballismus accompanied by ipsilateral acute limb pain at stroke onset, we retrospectively examined more than 4000 patients in the Lausanne Stroke Registry for hemiballismus-hemichorea occurring together with acute ipsilateral pain. RESULTS: Of the 29 subjects with hemiballismus-hemichorea, the observed patient was the only one to have acute pain at the onset of stroke. Magnetic resonance imaging showed acute infarction in the territory of the right anterior parietal artery, whereas the basal ganglia, thalamus, and subthalamic region were intact. CONCLUSIONS: The syndrome of acute limb pain associated with hemiballismus may result from disconnection of the parietal lobe from deeper structures. In contrast with isolated hemiballismus, we suggest that the simultaneous occurrence of this movement disorder with ipsilateral pain is specific for an anterior parietal artery stroke.

Aged↗

Aphasia in hyperacute stroke: language follows brain penumbra dynamics.

During the first few hours after onset, stroke symptoms may evolve rapidly. We studied the correlation between brain perfusion and aphasia changes during the hyperacute phase of stroke using a new technique of perfusion computed tomography (P-CT). Using an aphasia score developed for each language modality, language was evaluated within 6 hours after onset, then sequentially during the first week. Maps of the penumbra and infarct obtained from P-CT images and definite infarct size evaluated using T2 and diffusion-weighted MRI (DWI) on day 3 were rated by a neuroradiologist, blinded to the clinical deficit. Within 6 hours, deficits in all language modalities were present in 13 out of 24 consecutive patients, corresponding to large anterior-posterior perfusion deficits of the left middle cerebral artery (MCA) territory. The aphasia score correlated with a corresponding perfusion deficit in specific areas of the MCA territory, and showed significantly less improvement when the penumbra evolved toward infarction than when at least part of the penumbra was rescued. Our findings suggest a particularly good correlation between the evolution of aphasic symptoms and penumbra dynamics. Further studies on the relevance of penumbra dynamics in function-specific brain areas to decision taking in hyperacute stroke management are required.

Adult↗

Imaging of acute ischemic brain injury: the return of computed tomography.

PURPOSE OF REVIEW: Classical and modern computed tomography imaging techniques, including conventional computed tomography, perfusion-computed tomography and computed tomography-angiography for acute stroke are reviewed. RECENT FINDINGS: Thrombolysis has become an approved therapy for acute stroke. However, many stroke patients do not benefit from such treatment, since the presently used criteria are very restrictive, notably with respect to the accepted time-window. Even so, a significant rate of intracranial hemorrhage still occurs. Conventional cerebral computed tomography has been proposed as a selection tool for acute stroke patients. Recently, more modern computed tomography techniques, referred to as functional computed tomography or perfusion-computed tomography, have been introduced. Such perfusion-computed tomography techniques are competing favorably with diffusion-weighted/perfusion-weighted magnetic resonance imaging in the delineation of the penumbra. They are more easy to perform, because they are readily available and accessible in emergency settings, and less time-consuming. Furthermore, perfusion-computed tomography combined with computed tomography-angiography affords a comprehensive non-invasive survey of acute stroke patients as early as at the time of their emergency admission, with accurate demonstration of the site of arterial occlusion and its hemodynamic and pathophysiological repercussions for the brain parenchyma. SUMMARY: A renewal of computed tomography in the field of stroke has been afforded by the introduction of functional techniques such as perfusion-computed tomography, which provides promising insights into cerebral tissue viability and can be used as a guidance tool for therapy when combined with computed tomography-angiography.

Acute Disease↗

Vertebro-basilar syndromes causing oculo-motor disorders.

PURPOSE OF REVIEW: All functional classes of eye movements require exquisite coordination between cortical, basal ganglia and brainstem centers involved in ocular motor control. Vertebrobasilar stroke may produce a wide spectum of isolated or combined eye-movement disorders. The intent of this article is to summarize the curent knowledge of eye-movement disorders occurring in infarcts involving the different arterial territories of the vertebrobasilar circulation. RECENT FINDINGS: In the last few years there has been an improvement in our understanding of pathophysiological mechanisms that are related mainly to abnormal vergence disorders due to thalamic-subthalamic infarcts, as well as of the peculiar symptoms resulting from otolith pathway involvement occurring in lateral medullary infarcts. Moreover, progress in neuroimaging technology has implicated neurovascular contact of the trochlear nerve in instances of superior oblique myokimia. SUMMARY: Eye-movement disorders commonly occur in vertebrobasilar stroke, although they are often unappreciated. They may make it possible to establish specific anatomical correlates, as well as the probable nature of the underlying pathology.

Basal Ganglia↗

Occlusion due to carotid artery dissection: a more severe disease than previously suggested.

BACKGROUND: Stroke due to internal carotid artery dissection is considered to have a good prognosis. OBJECTIVE: To determine whether the prognosis of internal carotid artery dissection is worse than classically reported by comparing the characteristics of patients who had an acute ischemic stroke admitted to a population-based primary care center with internal carotid artery occlusion due to either dissection (DO) or atherothrombosis (AO). PATIENTS AND METHODS: Among 3502 patients admitted to our population-based primary care center, DO (n = 73) was diagnosed by angiography or magnetic resonance imaging, while AO (n = 81) was diagnosed by angiography. The characteristics of patients with DO or AO were compared using univariate and multivariate analysis. RESULTS: Patients with DO were younger (mean [SD] age, 44.6 [10] vs. 60.1 [10] years, P<.001), had fewer vascular risk factors, and presented more frequently with global middle cerebral artery territory involvement (42% vs. 17%, P<.05) and less frequently with watershed infarcts (3% vs. 19%, P<.05) than patients with AO. Unexpectedly, patients with DO were noted to have more severe clinical impairment, with an increased frequency of decreased consciousness, and a poorer outcome at 1 month. Multivariate analysis showed that the independent factors associated with DO were age younger than 55 years, nonsmoker, no history of hypertension, headache at presentation, and global aphasia. CONCLUSIONS: Patients with DO are younger and are initially seen with fewer risk factors than patients with AO, but their clinical features and prognosis are worse. Large infarcts involving the whole middle cerebral artery territory that may be due to the lack of collateral circulation are responsible for the bad prognosis of patients with DO.

Adult↗

Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients.

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.

Acute Disease↗