M. Hermier

Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study

BACKGROUND Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause of disability in children and in adults, and responds poorly to medical treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. Our aim was to test the effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP. METHODS We did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI. The primary endpoint was change in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as assessed with the Burke-Fahn-Marsden dystonia rating scale. The accuracy of surgical targeting to the GPi was assessed masked to the results of neurostimulation. Analysis was by intention to treat. FINDINGS The mean Burke-Fahn-Marsden dystonia rating scale movement score improved from 44.2 (SD 21.1) before surgery to 34.7 (21.9) at 1 year post-operatively (p=0.009; mean improvement 24.4 [21.1]%, 95% CI 11.6-37.1). Functional disability, pain, and mental health-related quality of life were significantly improved. There was no worsening of cognition or mood. Adverse events were related to stimulation (arrest of the stimulator in one patient, and an adjustment to the current intensity in four patients). The optimum therapeutic target was the posterolateroventral region of the GPi. Little improvement was seen when the neurostimulation diffused to adjacent structures (mainly to the globus pallidus externus [GPe]). INTERPRETATION Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome. FUNDING National PHRC; Cerebral Palsy Foundation: Fondation Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

Contribution of Susceptibility-Weighted Imaging to Acute Stroke Assessment

Background— Susceptibility-weighted (SW) MRI provides insight into the pathophysiology of acute stroke. We report on the use of SW imaging (SWI) sequences in clinical practice and highlight the future applications. Summary of Review— SWI exploits the magnetic susceptibility effects generated by local inhomogeneities of the magnetic field. The paramagnetic properties of deoxyhemoglobin support signal changes related to acute hemorrhage and the intravascular spontaneous blood oxygen level dependent (BOLD) effect. SWI allows the early detection of acute hemorrhage within 6 hours after symptom onset. SWI may also identify previous microbleeds in acute ischemia; however, the impact of these findings on thrombolytic therapy safety has not been definitely established. The diagnosis of arterial occlusion is usually performed by magnetic resonance angiography. SWI allows intravascular clot detection at the acute stage. Substantial experimental data suggest that spontaneous BOLD contrast may improve tissue viability assessment. The ratio of oxyhemoglobin to deoxyhemoglobin, measured by MRI in the capillary and venous compartments, reflects the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen. The combination of magnetic resonance (MR)-measured OEF and cerebral blood flow, via perfusion studies, may provide information about tissue viability. Conclusions— SWI offers a spectrum of current clinical applications and may improve our knowledge of the pathophysiology of acute stroke.

Thrombolysis for Ischemic Stroke in Patients with Old Microbleeds on Pretreatment MRI

Background: Old asymptomatic microbleeds (MBs) visualized on T2-weighted MRI are indicative of microangiopathy. They may be a marker of increased risk of intracerebral hemorrhage (ICH) following thrombolysis. However, data regarding this potential risk are limited. Methods: A retrospective analysis of pretreatment T2-weighted MRI was performed in consecutive stroke patients who received intravenous tissue plasminogen activator (tPA). We aimed to assess the impact of MBs on the risk of cerebral bleeding. The frequency and location of MBs were assessed and compared with the location of ICH after thrombolysis. Results: Forty-four patients were studied. MBs were present on pretreatment MRI in 8 cases (18.2%). At day 1, symptomatic ICH occurred in none of 8 patients with MBs versus 1 of 36 patients without (NS). At day 1, ICH occurred in 3 of 8 patients with MBs versus 10 of 36 patients without (NS). At day 7, symptomatic ICH occurred in 1 of 8 patients with MBs versus 2 of 36 patients without (NS). At day 7, ICH occurred in 5 of 8 patients with MBs versus 12 of 36 patients without (NS). No ICH occurred at the site of an MB. ICH occurred within the ischemic area in all patients who bled. Conclusions: Our study suggests that stroke patients with a small number of MBs on pretreatment MRI could be treated safely with thrombolysis. Larger prospective studies are needed to address the predictive value of detection of MBs with regard to the risk of tPA-induced ICH.

Clinical and imaging predictors of intracerebral haemorrhage in stroke patients treated with intravenous tissue plasminogen activator

Objective: To evaluate clinical, biological, and pretreatment imaging variables for predictors of tissue plasminogen activator (tPA) related intracerebral haemorrhage (ICH) in stroke patients. Methods: 48 consecutive patients with hemispheric stroke were given intravenous tPA within seven hours of symptom onset, after computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Baseline diffusion weighted (DWI) and perfusion weighted (PWI) imaging volumes, time to peak, mean transit time, regional cerebral blood flow index, and regional cerebral blood volume were evaluated. The distribution of apparent diffusion coefficient (ADC) values was determined within each DWI lesion. Results: The symptomatic ICH rate was 8.3% (four of 48); the rate for any ICH was 43.8% (21 of 48). Univariate analysis showed that age, weight, history of hyperlipidaemia, baseline NIHSS score, glucose level, red blood cell count, and lacunar state on MRI were associated with ICH. However, mean 24 hour systolic blood pressure and a hyperdense artery sign on pretreatment CT were the only independent predictors of ICH. Patients with a hyperdense artery sign had larger pretreatment PWI and DWI lesion volumes and a higher NIHSS score. Analysis of the distribution of ADC values within DWI lesions showed that a greater percentage of pixels had lower ADCs (<400×10−6 mm2/s) in patients who experienced ICH than in those who did not. Conclusion: Key clinical and biological variables, pretreatment CT signs, and MRI indices are associated with tPA related intracerebral haemorrhage.

Central nervous system cavernomas in the pediatric age group.

Abstract Pediatric CNS cavernomas still are diagnostically and therapeutically challenging lesions. With the help of magnetic resonance imaging, the natural history of cavernomas now guiding therapeutic strategies is well documented in adults but remains poorly known in the pediatric age group, since most previous studies dealt with adult and pediatric patients together. This paper focuses on clinical, imaging, and therapeutic features and differential diagnosis of CNS cavernomas with an emphasis on their specificities in the pediatric age group. It is based upon a critical review of the literature and our single-center experience with 36 children (35 with cerebral cavernomas and one with spinal cord cavernoma) operated on during the period of 1985–1999 as well as with seven additional unoperated pediatric cases. Our experience resembles that of other authors regarding the high hemorrhagic risk in children compared to adults. These angiographically occult vascular malformations are often revealed by the sudden onset of intracerebral hematoma with acute focal neurologic deficits, concomitant manifestations, and/or signs of raised intracranial pressure. True epilepsy is less common and may be related to chronic or recurrent microbleeding. Evocative imaging findings are also somewhat different in the two age groups, and we propose here an imaging classification of cerebral cavernomas based on both morphological and signal characteristics that is applicable to the pediatric age group. A sharply demarcated spherical intracerebral hematoma or heterogeneous lesion should always make one consider the hypothesis of a cavernoma. For symptomatic lesions and most rapidly growing asymptomatic lesions, the treatment of choice is complete microsurgical excision preceded by careful anatomical and functional evaluation. Improvements in surgical techniques and anesthesiology over recent years have brought good results in most operated children. The limited role of radiosurgery in the management of pediatric cerebral cavernomas is discussed. There is still a need for well-conducted specific evaluation of the natural history of these lesions in the pediatric age group to aid in systematic research, follow-up, and therapeutic strategies for asymptomatic cavernomas.

Intravenous tPA in acute ischemic stroke related to internal carotid artery dissection

Article abstract The authors describe the outcomes in 11 patients who had acute ischemic stroke related to internal carotid artery (ICA) dissection and were treated with IV tissue plasminogen activator (tPA). One symptomatic intracerebral hemorrhage occurred 36 hours after tPA was given. The mean day 90 modified Rankin Scale (m-RS) score was 2.4 (±1.6). No death was observed at 3 months. Four patients of 11 (36.4%) made an excellent recovery (day 90 m-RS score: 0 to 1). This study demonstrates the feasibility of IV thrombolysis with tPA (0.8 mg/kg) in ischemic stroke related to ICA dissection within the first 7 hours.

Inflammatory Response After Ischemic Stroke A USPIO-Enhanced MRI Study in Patients

Background and Purpose— The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume. Methods— We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests. Results— The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test (P=0.39) or Spearman test (P=0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement. Conclusions— USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.

Baseline Magnetic Resonance Imaging Parameters and Stroke Outcome in Patients Treated by Intravenous Tissue Plasminogen Activator

Background and Purpose— We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA). Methods— Patients with symptoms of acute hemispheric ischemic stroke were recruited. The National Institutes of Health Stroke Scale (NIHSS) score was assessed at baseline and at days 1, 7, and 60, and the modified Rankin scale (mRS) at day 60, by which outcome was classified in terms of independence (mRS score 0, 1, or 2) or severe disability or death (mRS score 3 through 6), was assigned. Multimodal stroke MRI was performed at presentation and repeated at day 1. MRI procedures included magnetic resonance angiography, T2* gradient-echo sequence, echoplanar imaging, and isotropic diffusion- (DWI) and perfusion-weighted (PWI) imaging. Patients were treated with intravenous rtPA after MRI completion. Results— Twenty-nine patients (16 men and 13 women; mean±SD age, 65±14 years) underwent MRI; the mean time from symptom onset to treatment was 255±62 minutes. Twenty-six patients had a vessel occlusion, and 15 patients experienced a partial (Thrombolysis in Myocardial Infarction [TIMI]-2) or total (TIMI-3) recanalization at day 1, whereas 11 patients had a persistent occlusion. Mean NIHSS scores at day 60 were 5.7±5.4 if recanalization had occurred and 14±2 in cases of persistent occlusion. According to the mRS, 13 patients were independent (mRS 0 through 2), whereas severe disability or death (mRS 3 through 6) was observed in 15 patients. A better outcome was observed when recanalization was achieved (r =−0.68, P =0.0002). PWI volume and time to peak (TTP) within the DWI lesion assessed before therapy were correlated with day-60 NIHSS score (PWI volume:r =0.51, P =0.006, TTP:r =0.35, P =0.07). The day-0 DWI abnormality volume was well correlated with day-60 NIHSS score (r =0.58, P =0.001). Multiple regression linear analysis showed that 2 factors mainly influenced clinical outcome: (1) recanalization, with a high correlation with NIHSS score at day 60 (P =0.0001) and (2) day-0 DWI lesion volume, which is closely associated with day-60 NIHSS score (P =0.03). Conclusions— Baseline DWI volume and recanalization are the main factors influencing clinical outcome after rtPA for ischemic stroke.

Cerebral venous thrombosis: Clinical outcome and systematic screening of prothrombotic factors

The authors studied 16 consecutive cases of cerebral venous thrombosis (CVT). Clinical outcome was good or excellent in 14 patients. Comprehensive hypercoagulable screening was done at least 3 months after the onset of CVT, including evaluation of genetic coagulation disorders and plasma levels of homocysteine and factor VIII. This screening was positive in 12 patients (75%). An acquired prothrombotic factor was identified in 9 of these 12 patients. Elevation of factor VIII plasma level was the most common coagulation disorder (8 patients).

Influence of pretreatment MRI parameters on clinical outcome, recanalization and infarct size in 49 stroke patients treated by intravenous tissue plasminogen activator

We hypothesized that pretreatment magnetic resonance imaging (MRI) parameters might predict clinical outcome, recanalization and final infarct size in acute ischemic stroke patients treated by intravenous recombinant tissue plasminogen activator (rt-PA). MRI was performed prior to thrombolysis and at day 1 with the following sequences: magnetic resonance angiography (MRA), T2*-gradient echo (GE) imaging, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Final infarct size was assessed at day 60 by T2-weighted imaging (T2-WI). The National Institutes of Health Stroke Scale (NIHSS) score was assessed prior to rt-PA therapy and the modified Rankin Scale (m-RS) score was assessed at day 60. A poor outcome was defined as a day 60 m-RS score >2. Univariate and multivariate logistic regression analyses were used to identify the predictors of clinical outcome, recanalization and infarct size. Forty-nine patients fulfilled the inclusion criteria. Baseline NIHSS score was the best independent indicator of clinical outcome (p=0.002). A worse clinical outcome was observed in patients with tandem internal carotid artery (ICA)+middle cerebral artery (MCA) occlusion versus other sites of arterial occlusion (p=0.009), and in patients with larger pretreatment PWI (p=0.001) and DWI (p=0.01) lesion volumes. Two factors predict a low rate of recanalization: a proximal site of arterial occlusion (p=0.02) and a delayed time to peak (TTP) on pretreatment PWI (p=0.05). The final infarct size was correlated with pretreatment DWI lesion volume (p=0.025). Recanalization was associated with a lower final infarct size (p=0.003). In conclusion, a severe baseline NIHSS score, a critical level of pretreatment DWI/PWI parameters and a proximal site of occlusion are predictive of a worse outcome after IV rt-PA for acute ischemic stroke.