Complete Remission in Paralytic Late Tick-Borne Neurological Disease Comprising Mixed Involvement of Borrelia, Babesia, Anaplasma, and Bartonella: Use of Long-Term Treatments with Antibiotics and Antiparasitics in a Series of 10 Cases.

This study aimed to demonstrate that severe neurological motor deficits in the context of late tick-borne disease with mixed microorganism involvement are eligible for long-term combined antibiotic/antiparasitic treatments. The inclusion criteria were: 1. neurological limb paralysis with a disability score >4 according to the EDSS Kurtzke disability scale; 2. serological tests pointing to an involvement of the main tick-borne microorganisms Borrelia burgdorferi s.l., Babesia, Anaplasma, and Bartonella; 3. a general disease for more than 6 months with fatigue, pain and subjective cognitive deficit. The patients were administered long-term treatments with repeated cycles (at least three) of 35-day IV ceftriaxone and repeated oral regimens of azithromycin-doxycycline and azithromycin-doxycycline-rifampicin. For Babesia, repeated courses of atovaquone-azithromycin were administered. Ten patients had intractable or severe motor deficits before treatment in the context of Borrelia (two cases) Borrelia-Babesia (four cases), Borrelia-Babesia-Anaplasma (two cases), Borrelia-Babesia-Anaplasma-Bartonella (one case) and Babesia-Anaplasma (one case). For several months, five had been in wheelchairs, and four had been walking with sticks. Seven patients out of 10 (70%) showed complete remission after a mean active treatment duration of 20.1 + 6.6 months, with a mean number of 4 ceftriaxone cycles. Three patients showed an initial remission but suffered secondary antibiotic/antiparasitic-resistant motor recurrences. Among the nine patients with Borrelia serologic positivity, treatments obtained complete remission in seven cases (77%). The findings of this ten-case series suggest the usefulness of long-term antibiotic/antiparasitic treatments in patients with severe late tick-borne neurological deficits with highly significant elements of tick-borne involvement.

Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis.

BACKGROUND AND PURPOSE: The purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). METHODS: In 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d-Dimers were measured at baseline, 2 and 24h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). RESULTS: Of 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2h: high FDP (p=0.01), high Log FDP (p=0.01), low fibrinogen (p=0.01), and low Log fibrinogen (p=0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p=0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p=0.01). The decrease in fibrinogen less than 2g/L multiplies the odds of early PH by a factor 12.82. CONCLUSION: An early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma.

Post-thrombolysis haemostasis changes after rt-PA treatment in acute cerebral infarct. Correlations with cardioembolic aetiology and outcome.

BACKGROUND: Little is known, in man, in the post-thrombolytic molecular dynamics of haemostasis, particularly the effect of rt-PA on antifibrinolytic components such as alpha2 anti-plasmin and Factor XIII. AIMS AND HYPOTHESIS: The purpose of this study was to systematically determine changes in coagulation and fibrinolytic parameters after thrombolysis with rt-PA during 24h. We also aimed to correlate these parameters with different acute ischemic stroke subtypes and global outcome. METHODS: Eighty consecutive patients with cerebral infarcts treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers measured at baseline (h0), 2 (h2) and 24h (h24) after initiation of thrombolysis. Correlations between the variations of these components were statistically studied, using the Spearman rank test or the Pearson test. These haemostatic parameters were also compared with cardioembolic and non cardioembolic patients, as well as between poor and favourable outcome patients. RESULTS: Between h0 and h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII was observed, while an increase in FDP and D-Dimers took place. These values returned to the initial levels at h24. At 2h, the decrease in fibrinogen was significantly correlated with that of plasminogen (0.48, p=0.01), alpha2-antiplasmin (0.48, p=0.004), and factor XIII (0.44, p=0.01); the decrease in plasminogen was significantly correlated with those of antifibrinolytic components, factor XIII (0.47, p=0.02) and alpha2-antiplasmin (r=0.77, p<0.001). These variations were independent of NIHSS. Cardioembolic infarcts showed a statistically significant greater h0-h2 decrease in plasminogen (p=0.04) and an h0-h2 increase in FDP (p=0.02). Poor outcome was linked to low plasminogen values at 2 and 24h. CONCLUSIONS: Supposed to be fibrin-specific, rt-PA induces a decrease in circulating fibrinogen, significantly linked to a decrease in plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII and alpha2-antiplasmin is also observed. At 2h, a significant decrease in plasminogen and a significant increase in fibrin(ogen) degradation products (FDP) are observed in cardioembolic infarcts, and appear as early independent predictors of this aetiology. A low plasminogen value at 2h is potentially predictive of poor prognosis at 3months.

Lack of association between air pollutant exposure and short-term risk of ischaemic stroke in Lyon, France.

BACKGROUND: Some observational and experimental studies have suggested a short-term relationship between air pollutants and ischaemic stroke; however, the results conflict. AIMS: The objective of this study was to investigate the association between particulate matter less than 2·5 and 10 microns in aerodynamic diameter, nitrogen dioxide, sulphur dioxide and ozone, and short-term risk of ischaemic stroke in Lyon, France. METHODS: The AVC69 study was a multicenter cohort study in which all consecutive adult patients admitted to one of the emergency or neurological departments of the Rhône area for suspicion of stroke were included during a seven-month period. Only patients with ischaemic stroke living within the study area, composed of Lyon and 18 neighbouring communities with homogenous air pollutants exposure, formed the basis of our study. We adopted a time-stratified case-crossover design to analyse the short-term effect (up to two-days) of air pollutants on ischaemic stroke incidence. Models were adjusted for temperature, variation of atmospheric pressure, minimal relative humidity, influenza epidemics, pollen count, and holidays. Stratified analyses by gender and class age were performed. Different lag times were analysed. RESULTS: 376 patients were included. Mean age was 76·6 years (± 13·7). 53·7% were women. No association was observed between air pollutants and short-term risk of ischaemic stroke after adjustment for main confounding factors. Results remained unchanged whatever the gender or age. CONCLUSIONS: These results suggest a lack of association between air pollutant exposure and short-term risk of ischaemic stroke in a French urban area.

Combined intravenous recombinant-tissular plasminogen activator and endovascular treatment of spontaneous occlusive internal carotid dissection with tandem intracranial artery occlusion.

Internal carotid artery (ICA) dissection with tandem internal carotid and middle cerebral artery occlusion may carry a poor prognosis even if intravenous recombinant-tissular plasminogen activator is administered. A better outcome may be expected with the combination of intravenous thrombolysis and endovascular methods (stenting and thromboaspiration). This procedure was performed in 3 patients who had concurrent ICA dissection and intracerebral occlusion. Endovascular treatment was feasible and safe. All our patients had a good clinical outcome. This potential effective approach may need further validation.

Symptomatic Moyamoya disease: clinical features and outcome after indirect bypass surgery in four French adults.

BACKGROUND: There are a few reports of moyamoya disease (MMD) in the European Caucasian adult population. We present the clinical manifestations, the neuroradiological aspects, the treatment, and the outcome after surgical revascularization of four French patients with MMD. PATIENTS AND METHODS: We identified four adults (age >18 years; three women and one man) with MMD who underwent digital subtraction catheter angiography at our institution from 1997 through 2006. The median age at symptom onset was 35 years (range, 22 to 41 years). The initial clinical presentation was intracerebral hemorrhage in three patients and ischemic stroke in one patient. RESULTS: Three patients underwent bilateral surgical revascularization and one patient underwent unilateral surgical revascularization. All patients underwent the same surgical revascularization procedure (encephalo-duro-arterio-myo-synangiosis). The mean (+/-SD) period of follow-up after diagnosis of MMD was 6 years and 9 months (+/-3 years and 5 months). No patient experienced any recurrent hemorrhagic or ischemic stroke. No perioperative stroke occurred. No patient was severely disabled or unable to walk. Three patients out of four were employed. CONCLUSION: Our data suggest safety and a potential benefit of surgical revascularization (indirect bypass surgery) in European adult patients with symptomatic MMD. Further long-term prospective multicenter studies are needed. The establishment of a registry would be useful in order to accumulate data in large numbers of European patients with this uncommon disease.

Nocturnal urine melatonin and 6-sulphatoxymelatonin excretion at the acute stage of ischaemic stroke.

Melatonin's neuroprotective action has been demonstrated in experimental models of brain ischaemia. The relationship between stroke and melatonin levels has been based on scarce and small sample size studies. In addition, the changes have not been correlated with the age of patients. We compared levels of nocturnal urinary melatonin and its metabolite, 6-sulfatoxymelatonin (aMT6S) in a large series of acute ischaemic stroke patients and healthy volunteers. Consecutive ischaemic stroke patients with a first episode of anterior circulation stroke were recruited. Urine samples were collected in 127 patients on day 1 poststroke and in a control population including 216 healthy volunteers, from 20:00 to 08:00 hr. Melatonin and aMT6S were measured by radioimmunoassay. Differences in melatonin and aMT6S levels between ischaemic stroke patients and healthy volunteers were assessed by gender and age categories, using the Student's t-test. Melatonin excretion was decreased in stroke patients compared with healthy volunteers (74.1 +/- 13.9 versus 211.9 +/- 31.0 ng/hr; P = 0.0004), whereas aMT6S level was not significantly reduced (6371 +/- 1028 versus 4469 +/- 508 ng/hr; P = 0.10). Conversely, the stratification by age showed a significant reduction of both melatonin and aMT6S levels among ischaemic stroke patients over 70 yr (P = 0.001 and P = 0.03 respectively). The impact of melatonin at the acute stage of stroke on clinical severity and lesion size needs further assessment, as melatonin may have potential neuroprotective effects.

Ipsilateral ptosis as main feature of tuberothalamic artery infarction.

Tuberothalamic artery infarction (TTAI) results mainly in a myriad of neuropsychological symptoms such as memory impairment, euphoria, apathy, verbal perseverations, constructional apraxia and lack of spontaneity. Language disturbances, acalculia, buccofacial and limb apraxia occur prominently after left TTAI while visual spatial processing deficits and hemispatial neglect occur prominently after the right one. Some cases of TTAI causing Horner's syndrome in addition of these wide-ranging neurobehavioral symptoms have been reported. Here, we report a case of TTAI with an ipsilateral ptosis as main clinical manifestation. This finding suggests that a Horner's syndrome can be the main feature of TTAI when neuropsychological manifestations are inconspicuous.

Stenting of symptomatic basilar and vertebral artery stenosis in patients resistant to optimal medical prevention: the lyon stroke unit experience.

UNLABELLED: Intracranial angioplasty stenting may be an efficient therapy in patients with intracranial atherosclerotic symptomatic vertebrobasilar artery stenosis unresponsive to optimal medical therapy. We present our experience in this setting. RESULTS: The study included 12 cases (8 men, 4 women), with an age range of 43-78 years (mean 62.6 years). Intracranial stenosis that resulted in qualifying stroke or transient ischemic attack involved the vertebral artery (n = 4), lower basilar artery (n = 1) and mid basilar artery (n = 5). Tandem stenosis included the intracranial vertebral artery and basilar artery (n = 1) and both intracranial vertebral arteries (n = 1). The degree of stenosis ranged between 70 and 90% in the basilar and vertebral arteries. Angioplasty + stenting was performed in all lesions. A successful procedure resulting in 30% of residual stenosis was found in 14 vessels. A periprocedural adverse event occurred in 1 case and was related to a brain hemorrhage. The mean patient follow-up was 15 +/- 3 months; 10 patients remained symptom free. All patients underwent a percutaneous endovascular balloon angioplasty and stent placement. CONCLUSIONS: This study supports the safety and the potential efficiency of stent-assisted angioplasty in patients resistant to optimal prevention. Randomized larger prospective trials are needed to confirm the benefit of this approach.

Recurrent cerebral venous thrombosis revealing paraneoplastic angiitis in Hodgkin's lymphoma.

Recurrent cerebral venous thrombosis (CVT), as a manifestation of paraneoplastic angiitis and revealing of nodular lymphocyte predominant Hodgkin's disease (NLPHD), is an extremely rare condition. We herein report a 55-year-old man who developed recurrent CVT despite efficacious anticoagulant therapy and subsequent stenting of the superior longitudinal sinus. Progressive neurological deterioration ensued and a body scan revealed axillary lymph nodes. Pathological analysis led to a diagnosis of NLPHD. Conventional angiography showed CVT and multiple arterial narrowings. A paraneoplastic primary cerebral angiitis with prominent venous structure involvement was suspected. Immunotherapy using rituximab and steroids provided a dramatic recovery. This case of CVT due to paraneoplastic cerebral angiitis is a rare condition and represents a new, very rare manifestation of nodular lymphocyte predominant Hodgkin's disease.

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.

Sinus venosus-type atrial septal defect: a rare curable cause of recurrent transient neurological deficits.

BACKGROUND AND PURPOSE: Sinus venosus defect is a rare cardiac abnormality, provoking an interatrial shunting outside the interatrial septum. Echographic diagnosis is difficult and may require examination by a specialized cardiologist. SUMMARY OF CASE: We report the case of a young woman who presented with repeated episodes of hemiparesis. CONCLUSIONS: Surgical correction of sinus venosus defect led to disappearance of neurological symptoms.

Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke.

BACKGROUND AND PURPOSE: Brain hemorrhage after ischemic stroke is a serious complication of treatment; however, its pathology is poorly understood. A classification based on brain imaging may help to better understand and avoid causal factors. METHODS: Review of the results of controlled randomized trials and the available literature. RESULTS: Hemorrhagic infarctions have no impact on clinical outcome and are probably not associated with the thrombolytic itself and the type of reperfusion strategy. They are associated with the extent of ischemic damage and most probably to an ischemic vasculopathy. Parenchymal hematomas are often clinically relevant. Their incidence is affected by the thrombolytic itself, the type, and probably the time point of reperfusion strategy. The loss of hemostatic control seems important in their pathogenesis. Extraischemic hematomas (remote from the infarct), unique or multiple, suggest pre-existing brain pathology, especially cerebral amyloid angiopathy. CONCLUSIONS: The radiological description of 3 different types of brain hemorrhage is useful to better understand the specific pathology and the impact on clinical outcome. It may help to avoid clinically relevant brain hemorrhages.

Anti-GAD antibodies and periodic alternating nystagmus.

BACKGROUND: Autoantibodies directed against glutamic acid decarboxylase (GAD-Ab) have recently been described in a few patients with progressive cerebellar ataxia, suggesting an autoimmune physiopathologic mechanism. OBJECTIVE: To determine the exact role of GAD-Ab and gamma-aminobutyric acid (GABA)-ergic neurotransmission in the pathogenesis of cerebellar ataxia. DESIGN: Case report. SETTING: University neurological hospital. PATIENT: We report the case of a patient with subacute cerebellar ataxia associated with GAD-Ab showing periodic alternating nystagmus (PAN). INTERVENTION: Baclofen, a GABAergic medication, was given to the patient. MAIN OUTCOME MEASURES: Eye movement recording of spontaneous nystagmus and postrotatory vestibular responses. RESULTS: Baclofen was effective in suppressing PAN and improving postrotatory vestibular responses but not for improving cerebellar ataxia. CONCLUSION: The presence of PAN and the response to baclofen provide a unique opportunity to suggest a direct role of GAD-Ab in cerebellar dysfunction in this patient.

Potential role of anti-GAD antibodies in abnormal eye movements.

Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid to gamma-aminobutyric acid (GABA). Autoantibodies directed against GAD (antiGAD-Ab) have been described in patients with insulin-dependent diabetes mellitus, stiff-man syndrome, and in a few patients with progressive cerebellar ataxia. The presence of these autoantibodies suggests an autoimmune pathophysiological mechanism for the neurological manifestations in these disorders. However, the exact role of antiGAD-Ab and GABAergic neurotransmission in the pathogenesis of the neurological manifestations, particularly in progressive cerebellar ataxia, is not fully understood. The cases of two patients with subacute cerebellar ataxia associated with antiGAD-Ab presenting with abnormal eye movements are reported. One patient presented a periodic alternating nystagmus (PAN), whereas the other presented a downbeat nystagmus (DBN) and slow vertical saccades. The potential role of antiGAD-Ab and the resultant GABAergic neurotransmission deficit in oculomotor manifestations is discussed.

Ethical issues of informed consent in acute stroke. Analysis of the modalities of consent in 56 patients enrolled in urgent therapeutic trials.

BACKGROUND: Many patients may be mentally incompetent or physically unable to give informed consent at the acute stage of stroke. Accordingly, we aimed to investigate the modalities of informed consent in urgent therapeutic stroke trials, the awareness of patients and relatives regarding stroke clinical trials and the impact of decision making on patients and relatives. METHODS: We present a study of 56 acute ischemic stroke patients who were randomized in 4 trials (2 trials testing neuroprotective agents, 1 testing thrombolysis and 1 testing antithrombotic agents). A standardized questionnaire was used to assess the modalities of informed consent in this setting. RESULTS: The mean age was 67.1 (SD 12.6) years. The mean baseline Scandinavian Stroke Scale (SSS) score was 23.8 (SD 10.5). Only 13 patients (23% of cases) gave consent while relatives gave consent for 43 patients (77%). The main reason for not getting consent from the patient was aphasia in 29 patients (67.4%). Multiple logistic regression analysis showed that the two independent factors influencing the ability to give consent are age and baseline neurological deficit as assessed by the SSS score. Concerning the psychological impact of consent, none of the 10 patients who answered our questionnaire declared feeling uncomfortable when giving consent, while 7 out of the 13 relatives who could be reached declared they felt uncomfortable, mainly because of the psychological stress induced by urgent decision making. CONCLUSIONS: Our study emphasizes the specific ethical difficulties of informed consent in the setting of acute stroke research. Only a minority of patients are able to give consent at the acute stage. Increasing age and neurological deficit are independent predictors of inability to give consent. Thus, the responsibility for consent usually relies on relatives with potential inaccuracy of decision concerning the patient's wish or even conflict of interest. Further evaluation of the psychological impact of decision on relatives is needed in this setting of acute stroke.

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.