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

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.

rtPA intravenous thrombolysis in anterior choroidal artery territory stroke.

OBJECTIVE: To study the possible specific response to recombinant tissue plasminogen activator (rtPA) thrombolysis of anterior choroidal artery (AChA) stroke. BACKGROUND: Outcome and response after rtPA thrombolysis are possibly better in small-vessel infarcts, but a specific study of AChA stroke has not yet been performed. METHODS: The authors proposed an open trial of IV rtPA within 7 hours in patients age 20 and 81 years with all types of internal carotid artery territory stroke if the baseline Scandinavian Stroke Scale (SSS) score was less than 48. A dose of rtPA 0.8 mg/kg was infused over 90 minutes. Of 114 consecutive patients, 9 patients (7.9%) exhibited hypodensity in the AChA territory on day 1 brain CT. RESULTS: Seven of nine patients with AChA infarct had a primary early recovery within 6 hours after the initiation of rtPA infusion. In addition, recovery was complete in five patients and partial in two patients. No intracerebral hematoma was observed. Three patients had a "reinfarct syndrome" at 12, 25, and 48 hours respectively. However, in the two latter patients treated with IV heparin, the deficit disappeared again with the increase of heparin dose in one patient and disappeared spontaneously in the other patient. The overall outcome at day 90 was six total recoveries in nine patients (66%). Patients with a final good outcome had a slight "unstructured" hypodensity in the AChA territory on day 1 brain CT, whereas patients with a bad outcome had the classic "structured" hypodensity of AChA territory stroke. CONCLUSION: These data support a specific quick response of AChA territory stroke to IV rtPA thrombolysis, probably due to the small size of the artery and of the "clot." The high frequency of the reinfarct syndrome is a clinical fact that is difficult to explain. Efficient heparin treatment after 24 hours may control the reinfarct syndrome in some patients.

Thrombolysis with intravenous rtPA in a series of 100 cases of acute carotid territory stroke: determination of etiological, topographic, and radiological outcome factors.

BACKGROUND AND PURPOSE: Although new, large, double-blind, randomized studies are needed to establish the efficiency of intravenous thrombolysis, open trials of sufficient size may also provide novel data concerning specific outcomes after thrombolysis. METHODS: An open study of intravenous rtPA in 100 patients with internal carotid artery (ICA) territory strokes between 20 and 81 years of age, with a baseline Scandinavian Stroke Scale (SSS) score of <48 at entry was conducted. Inclusion time was within 7 hours after stroke onset. rtPA (0.8 mg/kg) was infused for 90 minutes, with an initial 10% bolus. Heparin was given according to 3 consecutive protocols. The SSS evaluation was done on days 0, 1, 7, 30, and 90. CT scan was performed before treatment, on days 1 and 7. Etiological investigations included echocardiography and carotid Doppler sonography and/or angiography. Outcome at 1 year was documented by SSS score, the modified Rankin Scale (mRS) score, and a 10-point invalidity scale. Multivariate logistic regression was used to identify predictors of poor versus good outcome. RESULTS: At day 90, 45 patients (45%) had a good result, defined as complete regression or slight neurological sequelae (mRS score of 0-1), 18 patients had a moderate outcome (mRS 2-3), and 31 patients had serious neurological sequelae (mRS 4-5). Six patients died, 2 with intracerebral hematoma after immediate heparin. Five of 11 patients (45.5%) treated between 6 and 7 hours had a good result. The overall intracerebral hematoma rate was 7%. Higher values of fibrin degradation products at 2 hours were observed in the subgroup with intracerebral hematomas. Significant predictors of poor outcome on multivariate logistic regression analysis were baseline SSS score of <15 (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.07 to 10. 74; P=0.04), indistinction between white and gray matter on CT scan (OR, 6.59; 95% CI, 2.19 to 19.79; P=0.0008), and proximal internal carotid thrombosis (OR, 3.29; 95% CI, 0.99 to 10.95; P=0.05). CONCLUSIONS: Our study confirms the safety of intravenous rtPA at a dose of 0.8 mg/kg and suggests efficacy for this drug even within 7 hours. Outcome and hematoma rates were at least as favorable as for trials of therapy with a 3-hour time window. Subgroups with a poor prognosis include low baseline neurological score, baseline CT changes, and proximal ICA thrombosis. However, approximately 30% of patients with each of these characteristics show a good outcome, so their inclusion in future routine rtPA protocols is still justified.

Open trial of intravenous tissue plasminogen activator in acute carotid territory stroke. Correlations of outcome with clinical and radiological data.

BACKGROUND AND PURPOSE: Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized studies are needed, open trials could generate hypotheses concerning (1) the clinical correlations of outcome, (2) the significance of CT scan data during the first week, and (3) the use of adjunctive therapies. METHODS: We performed an open trial of intravenous rTPA on patients referred to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized during 1994 with completed stroke in the internal carotid artery territory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusion time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTPA was infused for 90 minutes. Intravenous heparin was given either immediately at efficient dosage or after 24 hours. Mannitol was used in patients with severe presentation. The Scandinavian Stroke Scale evaluation was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24 +/- 6 hours) and 7. RESULTS: Forty-three consecutive patients met the criteria of the protocol. The mean age at inclusion was 65 +/- 10.4 years, and the mean interval to treatment was 232 +/- 79 minutes. At day 90, 25 patients (58.1%) exhibited a complete regression of symptoms, and 3 had moderate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas. Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated with major neurological improvement at day 1. Intravenous immediate heparin versus delayed heparin after 24 hours improved the ischemic outcome but not the overall outcome. Reinfarction syndromes after major neurological improvement, likely to be rethrombosis syndromes, were observed in 3 patients (6.9%). For the day 1 CT scan, poor outcome was associated with the presence of structured and homogeneous hypodensities likely to represent classic infarcts, as confirmed by day 7 CT scan. Conversely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases and is likely to represent reperfusion images and/or incomplete ischemic damage. CONCLUSIONS: The results obtained in this open, small study suggest safety and effectiveness of rTPA thrombolysis at the dose of 0.8 mg/kg within 7 hours in acute strokes of the carotid territory, including highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during the first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylobar and heterogeneous, which is likely to correspond to reperfusion images.

[Treatment of Wilson's disease with zinc. 5 cases]. / Traitement de la maladie de Wilson par le zinc. Cinq cas.

Zinc treatment of Wilson's disease was introduced by Schouwink en 1961 and is still uncommon in France. We evaluated the effectiveness and safety of zinc in 5 patients with Wilson's disease aged from 19 to 40 years. There were three neurological, one hepatic and one asymptomatic cases. Zinc was administered in doses of 120 to 272 mg/day, alone in 3 cases and combined with D-penicillamine in 2 cases. After 1 to 7 years of zinc therapy, our experience is consistent with data from recent literature and provides further evidence of zinc effectiveness. Zinc may be prescribed as first treatment in most patients, including asymptomatic cases. The only exception concerns patients with severe symptoms in whom it is recommended to combine zinc with D-penicillamine during the early phase of treatment for more rapid effectiveness. Because of its safety, zinc is particularly indicated in cases of intolerance to D-penicillamine and trien.

[Neurological manifestations in the vertebro-basilar system suggesting pregnancy toxemia]. / Manifestations neurologiques en territoire vertébro-basilaire révélatrices d'une toxémie gravidique.

Early CT scan showed a large hypodensity throughout midbrain. Brainstem auditory evoked potential showed initially an abolition of III and V pikes suggesting brainstem injury. Two days later neurologic examination and brain stem auditory evoked potential returned to normal. CT scan performed three weeks after the onset was normal. These finding suggest a vasospasm; in this case betasympathomimetic agents given two weeks before the onset of toxemia for preterm labor could lead to the vasospasm.

[Neurologic manifestations in the vertebro-basilar system revealing pregnancy toxemia]. / Manifestations neurologiques dans le territoire vertebro-basilaire révélatrices d'une toxémie gravidique.

We report a case with focal neurological deficits suggesting vertebro-basilar system ischemia, in the course of pre-eclampsia. An early CT scan showed a large hypodensity throughout the midbrain. Brainstem auditory evoked potentials initially showed an abolition of III and V pikes suggesting brainstem injury. Two days later both neurological examination and brain stem auditory evoked potentials returned to normal. A CT scan performed three weeks after the onset was normal. These findings suggest a vasospasm which may have been due to sympathomimetic agents given two weeks before the onset of toxemia for preterm labor.

[Cerebellar imitation synkineses]. / Syncinésies d'imitation cérébelleuses.

Two patients with autosomal dominant pure cortical cerebellar atrophy, belonging to the same family, exhibited imitation synkineses of hands and feet when the contralateral extremity was moved. The phenomenon was observed particularly when alternate movements of one hand were performed, but it also existed when flexion-extension movements of one foot took place. The induced synkinetic movements were mainly observed on the right side in one patient and exclusively observed on the right side in the other one. At electromyography, the imitation synkinesis took place about 200 milliseconds after the first inducing movement, but tended to be simultaneous with the following ones. Imitation synkinesis appeared to be shared by other cerebellar conditions: 8 cases of sporadic pure cerebellar atrophy and 2 cases of post-surgical injury of the anterior lobe vermis. In the 2 genetic cases, there was no pyramidal sign nor sensitive disturbance, the somesthesic evoked potentials being normal. Thus, the imitation synkinesis was considered as having a cerebellar origin. The cerebellar imitation synkinesis might be provoked by the lack of a physiologic cerebellar inhibition located in the paleo- and/or neo-cerebellum. The predominance of imitation synkineses on the right side suggests that cerebellar inhibition is stronger for the dominant side, in order to liberate it from archaic synkineses.

[Intensive immunosuppression in progressive multiple sclerosis. An open study comparing 3 groups: cyclophosphamide, cyclophosphamide-plasmapheresis and control subjects. Results after 3 years]. / Immunosuppression intensive dans la sclérose en plaques progressive. Etude ouverte comparant trois groupes: cyclophosphamide, cyclophosphamide-plasmaphérèses et témoins. Résultats à trois ans.

Three groups of 10 patients each with multiple sclerosis (MS) in a progressive phase were openly matched on the basis of age and invalidity (DSS Kurtzke). Variance analysis showed no significant difference between them for the main MS features. Group 1 received cyclophosphamide for 3 weeks (mean total dose: 152 mg/kg) with methylprednisolone (mean total dose: 2.77 g). Group 2 had a mean number of 9 plasma exchanges prior to a cyclophosphamide-methylprednisolone regimen similar to Group 1 (mean total dose of cyclophosphamide: 160 mg/kg and of methylprednisolone: 3.16 g). Group 3 was made up of controls. At three years, the proportion of stabilized and improved cases was 6/10 in group 1, 9/10 in Group 2 (statistically significant when compared with Group 1), and 0/10 in Group 3. The study of the variations of invalidity (DSS gains) showed a clear significant benefit in the treated groups when compared to controls, but no difference between the treated groups. Longitudinal studies showed that the mean therapeutic benefit was about 2.5 years. The role of cyclophosphamide and of plasma exchanges in these results is discussed.

Evoked potential studies in Friedreich's ataxia and progressive early onset cerebellar ataxia.

We recorded somatosensory evoked potentials (SEP) in 15 patients affected by Friedreich's ataxia (FA) and in 9 patients with progressive early onset cerebellar ataxia (PEOCA). Brainstem auditory evoked potentials (BAEP) were also recorded in 14 FA patients and in five PEOCA patients. SEP results showed clear differences between groups of FA, evidence of peripheral involvement was seen in all patients, with absence of the N9 potential or a major reduction of its amplitude. In patients in whom central responses could be recorded, conduction velocity was normal or near normal up to the brainstem but was reduced from brainstem to cerebral cortex. Four patients with PEOCA had SEP abnormalities similar to those seen in FA. In the five other patients, the amplitude and latency of N9 were normal but conduction velocity was reduced from brainstem to cerebral cortex. In FA, BAEP were abnormal in all patients with a disease duration of four years or more but were normal in four of the five PEOCA patients. Systematic evoked potential recording is useful in the investigation of hereditary ataxias.

[Rapid modification of the symptomatology of progressive forms of multiple sclerosis by plasma exchange]. / Modification rapide par les échanges plasmatiques de la sémiologie de formes progressives de la sclérose en plaques.

Twelve consecutive patients with a progressive form of multiple sclerosis were submitted to 6 sessions of plasma exchange as single therapy. Results were evaluated by Mac Alpine's, Kurtzke's, a simplified semi-quantitative neurologic validity scale and by determination of 4 totally objective quantitative parameters. A decrease in the disability score, according to Kurtzke, was noted in 4 patients, and comparison of scores of neurologic validity before and after plasma exchange showed a highly significant difference (p less than 0.0001). A significant effect was noted also for two of the quantitative parameters. The effect was predominant on pyramidal and cerebellar disorders. Improvement was rapid but transient and did not persist after 2 months. Theoretically, this improvement after plasma exchange implies the existence of circulating neuro-inhibitory factors and that multiple sclerosis is a disease not limited to the central nervous system. Indications for plasma exchange in the progressive form of multiple sclerosis are discussed.

[Encephalopathy during distomiasis]. / Encéphalopathie au cours d'une distomatose.

A patient with Fascioliasis developed polyradiculoneuritis and encephalopathy. The diagnosis was confirmed by an eosinophilia associated with positive serial serology tests. The disease regressed spontaneously. The immuno-allergic mechanism is discussed.