Caroline Ottomeyer

Gender Differences in Acute Ischemic Stroke: Etiology, Stroke Patterns and Response to Thrombolysis

Background and Purpose— Differences between women and men in relation to stroke are increasingly being recognized. Methods— From July 2004 until June 2007, 237 acute ischemic stroke (AIS) patients were treated with recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of women were compared to those of men. Results— Of 237 AIS patients (mean age 70.7 years), 111 (46.8%) were women and 126 (53.2%) were men. Women were older (P=0.001), but history of hyperlipidemia (P=0.03), smoking (P=0.03), and coronary heart disease (P<0.001) was less frequent than in men. Internal carotid artery disease occurred more often in men (P=0.02), whereas atrial fibrillation was observed more often in women (P=0.002). In men borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%), whereas women showed a higher percentage of large territorial stroke (72.8 versus 60.3%, P=0.09). Baseline National Institute of Health Stroke Scale scores (12.5 versus 11.3), NIHSS score at discharge (11.0 versus 9.5), 3-month-outcome modified Rankin Scale score, thrombolysis-related (17.1% versus 13.5%) or independent complications (32.4% versus 30.2%), and mortality after 3 months (13.5% versus 9.5%) were similar. Conclusion— Differences of stroke lesion patterns in genders are paralleled by differences in etiology and risk factor profiles (women, cardioembolism; men, large and small vessel disease). Baseline characteristics, rates of rtPA-related and independent complications, as well as clinical outcomes were not different between women and men with AIS.

Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET

Sirs, Non-paraneoplastic limbic encephalitis (NPLE) often results in an unfavorable clinical course with progressive neuropsychological deficits and epileptic seizures despite treatment [1–3]. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDGPET) and antibodies against voltage-gated potassium channels (VGKC-Ab) are helpful in monitoring the course of the disease [3–5]. We present a follow-up of a NPLE patient over a 3-year period with successive affection of bilateral temporomesial structures. A 67-year-old man with no relevant medical history presented with recurrent episodes of visual hallucinations, memory impairment, disorientation and myoclonic jerks. Neurological examination was unremarkable; however neuropsychological testing revealed severe verbal (shortterm) memory, speech fluency and visual recognition deficits. EEG showed an intermittent theta-focus as well as intermittent right temporal ictal rhythmic activity. On MRI hyperintensity and diffuse swelling of the right hippocampus on T2and diffusion-weighted (DWI) images was found. FDG-PET revealed right temporomesial hypermetabolism and bilateral hypometabolism in the temporal lobes (Fig. 2a). There were no signs of tumor in the wholebody PET examination. CSF (including virological analysis) was normal except for elevated VGKC-Ab levels ([9085 pM, controls \100 pM). Thyroid function and autoantibodies tests were negative. The diagnosis of NPLE was made and methylprednisolone (MP; 4000 mg i.v. over 5 days) as well as gabapentin treatment was initiated. Figure 1 shows the course of the disease, examination results and therapeutic management. Three months later, the patient presented with a deterioration of symptoms. MRI showed an atrophy of the right hippocampus, with mild residual T2-hyperintensity. FDGPET showed left temporal hypermetabolism and a right temporomesial ‘‘cold’’ lesion (Fig. 2b). VGKC-Ab were still elevated ([8067 pM). Treatment with MP (5000 mg i.v. over 5 days) was started again. Six months later he was re-admitted with progressive memory impairment, confirmed by neuropsychological examination. Now on MRI, left hippocampal edema was found and FDG-PET demonstrated severe hypometabolism in both temporomesial regions. After 2 months of stable condition, there was once again neuropsychological deterioration. There were no significant changes on MRI compared to the previous examinations and the FDG-PET showed left temporomesial hypometabolism. IV immunoglobulin therapy (150 g over 3 days) was applied. Two and 4 months later MRI and FDG-PET findings remained unchanged. VGCK-Ab levels were almost normal. Memory impairment had temporarily deteriorated before improving again, this time under immunosuppressive treatment with azathioprine (100 mg/ d). At the last two visits (after 2 and 3.5 years) the patient was seizure-free under gabapentin and showed an improvement of his cognitive functions under azathioprine treatment. MRI showed left hippocampal atrophy and FDG-PET hypometabolism in both temporomesial areas (Fig. 2c). A neoplasm was excluded by repeated wholebody PET examinations. In NPLE, neuropsychological deficits often remain or deteriorate even if seizures are controlled and immunosuppressive treatment is applied. In our case, disease A. Chatzikonstantinou (&) K. Szabo C. Ottomeyer R. Kern M. G. Hennerici Department of Neurology, Universitatsklinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail: chatziko@neuro.ma.uni-heidelberg.de

[Orolingual angioedema under systemic thrombolysis with rt-PA: an underestimated side effect].

BACKGROUND Orolingual angioedema (OA) is an unappreciated complication of acute stroke treatment with recombinant tissue plasminogen activator (rt-PA). It has been described in 2% of patients receiving thrombolysis, and it seems that patients taking angiotensin-converting enzyme inhibitors are especially at risk. Even though the presentation is generally unilateral and limited to lips and tongue, an extension of edema to the oropharynx may lead to life-threatening upper airway obstruction. MATERIAL AND METHODS In a retrospective analysis of clinical data of 407 patients treated with systemic rt-PA thrombolysis between January 2006 and October 2008 in our department, we describe the occurrence and clinical presentation of OA. RESULTS Nine of 407 patients (2.2%) showed clinical signs of OA. Typical presentations of OA are illustrated in case reports describing two of these patients and are completed by an overview of the current literature. DISCUSSION Besides prophylactic inspection of the oral cavity during and after thrombolysis, therapeutic options in case of OA include early intravenous antihistaminergic therapy and protective intubation.

Raising Awareness of Orolingual Angioedema as a Complication of Thrombolysis in Acute Stroke Patients

1 Sundt TM, Sharbrough FW, Piepgras DG, Kearns TP, Messick JM, O’Fallon WM: Correlation of cerebral blood flow and electroencephalographic changes during carotid endarterectomy. Mayo Clin Proc 1981; 56: 533–543. 2 van Mook W, Rennenberg R, Schurink G, et al: Cerebral hyperperfusion syndrome. Lancet Neurol 2005; 4: 877–888. 3 Russell DA, Gough MJ: Intracerebral haemorrhage following carotid endarterectomy. Eur J Vasc Endovasc Surg 2004; 28: 115–123. 4 Abou-Chebl A, Yadav JS, Reginelli JP, Bajzer C, Bhatt D, Krieger DW: Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting: risk factors, prevention, and treatment. J Am Coll Cardiol 2004; 43: 1596–1601. 5 Doelken M, Lanz S, Rennert J, Alibek S, Richter G, Doerfler A: Differentiation of cytotoxic and vasogenic edema in a patient with reversible posterior leukoencephalopathy syndrome using diffusion-weighted MRI. Diagn Interv Radiol 2007; 13: 125–128. 6 Tsukimori K, Ochi H, Yumoto Y, et al: Reversible posterior encephalopathy syndrome followed by MR angiography-documented cerebral vasospasm in preeclampsia-eclampsia: report of 2 cases. Cerebrovasc Dis 2008; 25: 377–380. 7 Toh CH, Wong HF, Lin TK, Ng SH: Abnormal enhancement on imaging studies preceding hyperperfusion syndrome. Case illustration. J Neurosurg 2006; 105: 932. 8 Karapanayiotides T, Meuli R, Devuyst G, et al: Postcarotid endarterectomy hyperperfusion or reperfusion syndrome. Stroke 2005; 36: 21–26. 9 Oehm E, Hetzel A, Els T, et al: Cerebral hemodynamics and autoregulation in reversible posterior leukencephalopathy syndrome caused by pre-/eclampsia. Cerebrovasc Dis 2006; 22: 204–208. 10 Suga Y, Ogasawara K, Saito H, et al: Preoperative cerebral hemodynamic impairment and reactive oxygen species produced during carotid endarterectomy correlate with development of postoperative cerebral hyperperfusion. Stroke 2007; 38: 2712–2717.

Dynamic Susceptibility Contrast Perfusion MRI Identifies Persistent Vessel Pathology in Acute Pontine Stroke

Background: In large territorial stroke of the anterior and the posterior circulation, the extent of affected tissue can be characterized by the demonstration of vessel occlusion on MR angiography (MRA), while the extent of hypoperfusion can be shown on dynamic susceptibility contrast perfusion-weighted MRI (PWI). The ability of MRA and conventional MRI sequences to demonstrate branches of the basilar artery (BA) is very limited. This study analyzes the value of the combined use of diffusion-weighted MRI (DWI), MRA and PWI in acute pontine stroke. Methods: A series of 24 consecutive patients with acute pontine stroke received an extensive MRI stroke workup including DWI, PWI and MRA. Results: In 11/24 patients visual analysis of PWI demonstrated persisting hypoperfusion, and in 1/24 patients indication of hyperperfusion was found. Vessel abnormalities were seen in 19/24 patients (15/24 hypoplastic vertebral artery, 9/24 stenosis or occlusion of the BA, 1/20 ectatic BA). Persistent pontine hypoperfusion was more frequently associated with BA pathology (9/11 vs. 1/13, p = 0.001), large-vessel disease (8/11 vs. 1/13; p = 0.001) and a more pronounced clinical deficit (NIHSS score on day 1: 7 vs. 3, p = 0.01). Conclusions: In pontine ischemia areas of hypoperfusion can be identified due to the strong contrast induced by ischemia on PWI and can be easily related to DWI lesion size. This is of use particularly as small vessels are frequently missed by MRA and occlusion of the BA can be better characterized with the help of PWI.

Cerebral network disruption as a possible mechanism for impaired recovery after acute pontine stroke.

Background: Recovery from stroke is presumed to be a function of a widespread cerebral network. Chronic white matter lesions (WML) have been proposed to be a predictor of poor outcome after acute stroke. We tested the hypothesis that the extent of WML has an effect on functional recovery in acute pontine stroke by disrupting the integrity of the supratentorial cerebral network. Methods: Seventeen patients with acute unilateral pontine stroke who had received a standardized stroke workup and additional diffusion tensor imaging (DTI) were studied. After grading the extent of WML according to the Fazekas scale and semiautomated lesion volume calculation, we compared patients with acute pontine infarction and advanced WML to those with absent or minimal WML regarding baseline characteristics, stroke subtype and clinical outcome. In addition, we used tract-based spatial statistics for voxel-wise analysis of the DTI-derived parameter fractional anisotropy in the white matter tracts. Results: The volume of WML ranged between 0.1 and 42.1 cm3 (mean = 15.9) and was graded as follows: 0 in 5.9%, 1 in 35.3%, 2 in 41.2% and 3 in 17.6%. Both patients with Fazekas grades 2–3 (p = 0.014) as well as those with larger WML volumes (p = 0.037) had severer functional deficits at the 3-month follow-up. White matter tracts displaying a significant decrease in fractional anisotropy values were the corpus callosum, the anterior thalamic radiation and the inferior fronto-occipital fasciculus. Conclusions: Chronic WML contribute to a less favorable clinical outcome after pontine stroke depending on (1) the extent of pre-existing WML and (2) the degree of disruption of cerebral connectivity as indicated by reduced tissue integrity in the white matter not affected by WML as detected by DTI and tract-based spatial statistics.

Orolinguales Angioödem unter systemischer Thrombolyse mit rt-PA

BACKGROUND Orolingual angioedema (OA) is an unappreciated complication of acute stroke treatment with recombinant tissue plasminogen activator (rt-PA). It has been described in 2% of patients receiving thrombolysis, and it seems that patients taking angiotensin-converting enzyme inhibitors are especially at risk. Even though the presentation is generally unilateral and limited to lips and tongue, an extension of edema to the oropharynx may lead to life-threatening upper airway obstruction. MATERIAL AND METHODS In a retrospective analysis of clinical data of 407 patients treated with systemic rt-PA thrombolysis between January 2006 and October 2008 in our department, we describe the occurrence and clinical presentation of OA. RESULTS Nine of 407 patients (2.2%) showed clinical signs of OA. Typical presentations of OA are illustrated in case reports describing two of these patients and are completed by an overview of the current literature. DISCUSSION Besides prophylactic inspection of the oral cavity during and after thrombolysis, therapeutic options in case of OA include early intravenous antihistaminergic therapy and protective intubation.

Aphemia: an isolated disorder of speech associated with an ischemic lesion of the left precentral gyrus

Sirs, Aphemia, also termed apraxia of speech, cortical anarthria or pure word mutism, is an isolated disorder of coordinated speech articulation that results in severe affection of verbal motor output [8, 9]. This rare and possibly underdiagnosed syndrome was first postulated by Paul Broca in 1861 [1]; however, the definition remained imprecise during the course of history. Especially the differentiation between aphemia and aphasia—the latter of which was shortly after described by Armand Trousseau— as well as dysarthria has been in discussion since then. A 61-year-old right-handed dentist with treated hypertension awoke with acute loss of speech and saliva running out of the right corner of his mouth. He wrote ‘‘stroke’’ on a piece of paper for his wife, who called the ambulance. In the emergency room, he was nearly mute due to grossly distorted motor output, but he had full comprehension of speech, could communicate through gestures and intact, fluent writing (Fig. 1a). Speech was very difficult with strangled vowels, severe phonematic paraphasia and abnormal prosody that was not facilitated by singing, reading or repetition. This and the constant effort to correct himself cumulated in visible frustration, whereas, surprisingly, the patient was able to produce—apparently emotionally triggered—short, but intact and fluently articulated commentaries of the situation (e.g., ‘‘It’s not working!’’, ‘‘That’s terrible!’’). There was a mild right facial palsy without further affection of coordinated buccofacial movement (whistling, etc.) or oropharyngeal sensibility (NIHSS 4). Diffusion-weighted MRI performed shortly after presentation to the emergency room showed an acute ischemic lesion of the left precentral gyrus that was not yet visible on T2-weighted FLAIR images. The lesion extended slightly to the medial part of the premotor cortex (Fig. 2). Ultrasound and MRA demonstrated a highgrade stenosis of the left internal carotid artery (ICA). As extensive stroke workup failed to show an alternative source of embolism, symptomatic ICA stenosis was considered the most likely cause of stroke, and the patient was treated with endarterectomy on day 4. Under speech therapy, the symptoms improved gradually, and speech became more and more fluent after day 3. In the beginning, syntax presented incompletely because of the effort of speech, but became intact by day 3. From day 1, repeated dictations and spontaneous essays (see Fig. 1b) could demonstrate the constantly fluent and intact written language. During observation, dysarthric components never occurred. At 1 week, the patient recovered completely, including the right facial palsy. Still not clearly classified as an articulatory or language disorder, aphemia is today understood as an isolated disorder of the planning of motor articulation of speech. These patients, even when mute, can write correctly and have no difficulty in the production of verbal sequences as long as they do not have to articulate them, distinguishing the disorder from motor aphasia. The presentation of abnormal prosody, ‘‘false starts,’’ self corrections and the occurrence of undisturbed ‘‘insulas’’ in speech can help to differentiate it from dysarthria. Often, right-sided hemiparesis, limb apraxia, mild buccofacial apraxia and central right facial palsy are associated symptoms. The lesion of the precentral gyrus corresponds to recent data of the few similar cases published [2, 5, 7]. These case studies have linked the C. Ottomeyer (&) B. Reuter T. Jager C. Rosmanith M. G. Hennerici K. Szabo Department of Neurology, Universitatsklinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail: c.ottomeyer@neuro.ma.uni-heidelberg.de

Orolinguales Angioödem unter systemischer Thrombolyse mit rt-PA@@@Orolingual angioedema under systemic thrombolysis with rt-PA: Eine unterschätzte Nebenwirkung@@@An underestimated side effect

BACKGROUND Orolingual angioedema (OA) is an unappreciated complication of acute stroke treatment with recombinant tissue plasminogen activator (rt-PA). It has been described in 2% of patients receiving thrombolysis, and it seems that patients taking angiotensin-converting enzyme inhibitors are especially at risk. Even though the presentation is generally unilateral and limited to lips and tongue, an extension of edema to the oropharynx may lead to life-threatening upper airway obstruction. MATERIAL AND METHODS In a retrospective analysis of clinical data of 407 patients treated with systemic rt-PA thrombolysis between January 2006 and October 2008 in our department, we describe the occurrence and clinical presentation of OA. RESULTS Nine of 407 patients (2.2%) showed clinical signs of OA. Typical presentations of OA are illustrated in case reports describing two of these patients and are completed by an overview of the current literature. DISCUSSION Besides prophylactic inspection of the oral cavity during and after thrombolysis, therapeutic options in case of OA include early intravenous antihistaminergic therapy and protective intubation.