Philippe Lyrer

Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection

Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defined by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass effect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be difficult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confirm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissections

Background Cervical artery dissection (CAD) is a frequent cause of ischemic stroke, and occasionally death, in young adults. Several lines of evidence suggest a genetic predisposition to CAD. However, previous genetic studies have been inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact. Our aim is to identify genetic variants associated with an increased risk of CAD and possibly gene-environment interactions. Methods We organized a multinational European network, Cervical Artery Dissection and Ischemic Stroke Patients (CADISP), which aims at increasing our knowledge of the pathophysiological mechanisms of this disease in a large group of patients. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, DNA from approximately 1100 patients with CAD, and 2000 healthy controls is being collected. In addition, detailed clinical, laboratory, diagnostic, therapeutic, and outcome data are being collected from all participants applying predefined criteria and definitions in a standardized way. We are expecting to reach the above numbers of subjects by early 2009. Conclusions We present the strategy of a collaborative project searching for the genetic risk factors of CAD. The CADISP network will provide detailed and novel data on environmental risk factors and genetic susceptibility to CAD.

Outcome of Intravenous Thrombolysis in Stroke Patients Weighing over 100 kg

Background: Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. Methods: Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0–2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. Results: Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). Conclusion: Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.

Vertebral artery dissection presenting with fifth cervical root (C5) radiculopathy

Sirs: Peripheral motor deficits in the upper limb are rare manifestations of vertebral artery dissection (VAD) [1–6]. In cervical spine MRI signs of VAD may remain unrecognised. The case reported here highlights the need to exclude VAD in otherwise unexplained radiculopathies of the upper cervical cord. A white 52-year-old waiter presented with severe proximal weakness of the left arm. Three weeks prior to presentation he had sustained minor trauma with bruises to the right chest and ten days later developed left-sided neck pain without radiation to the arms. Three days before presentation he noticed difficulties at work when serving his guests, because he could neither elevate nor rotate the left shoulder. His past medical history was significant only for vaccinations (polio, hepatitis A and tetanus) three months before. He has no family history of neuromuscular diseases. On admission severe weakness of the following muscles was observed on the left: deltoid (2/5), supraspinatus (2/5), infraspinatus (2/5) and biceps (3/5). Biceps and brachioradialis reflexes were absent and no sensory deficit was detected. The remainder of the neurological and physical exam was unremarkable. A C5 radiculopathy was suspected on clinical grounds, probably due to a disc herniation. Since there was neither radiating pain nor a sensory deficit infectious radiculopathy and idiopathic plexus neuritis were considered in the differential diagnosis. In the CSF, however, cell count and protein were within normal limits and the Lyme serology was negative. Cervical MRI (Fig. 1 A and B) showed no relevant discopathy, but revealed a dissection of the left vertebral artery from C7 to C2 indicated by an intramural haematoma (open and thin arrows) in close relationship to the nerve root (filled arrows). MRangiography (Fig. 1 C) demonstrated a narrowed lumen of the extracranial left vertebral artery. Neurosonography revealed enlarged vessel diameter and narrowed vessel lumen of the V2segment of the left vertebral artery without intimal flap or haemodynamic changes. Diagnosis of left subadventitial extracranial VAD compressing the C5 nerve root was made. Electromyography confirmed an isolated acute denervation process of the C5 innervated muscles of the left arm. Therapy with acetylsalicylic acid (100 mg) was started [7]. The weakness resolved within four weeks. We found eight other published cases of VAD with severe weakness of C5 and C6 innervated muscles as the only presenting symptom [1–6]. Patients were young (mean age 35.4 years), the delay between initial pain and occurrence of weakness ranged from three to ten days (mean 7.2 days). Neck pain was reported in eight patients, local pain in the shoulder or arm in four. Weakness was most prominent in the deltoid muscle in all cases, slight numbness in the upper arm occurred in five. All had a full recovery after one to five months. None suffered from stroke or TIA during followup. Cases of VAD presenting only with peripheral motor deficits may be underdiagnosed due to a more benign clinical course and the difficulties in establishing the diagnosis. MRI is the preferred technique for spine imaging, but subtle signs of VAD may be missed in the first few days, because the hyperintensity of the intramural haematoma on T1 weighted images is not visible until the formation of methaemoglobin [8, 9]. Here, neurosonography may provide useful information about altered vertebrobasilar perfusion and nonatherosclerotic arterial wall alterations. The close anatomical relationship between the vertebral artery in the intraforaminal part and the anterior motor part of the nerve roots suggests a compressive aetiology due to mural haematoma in the vessel wall [1, 2, 5]. Alternatively, VAD may compromise the perfusion in the vasa nervorum and result in nerve root ischaemia. The C5 root seems to be the most susceptible root. M. Hardmeier (&) AE A. Steck AE P. Lyrer S. Engelter AE S. Renaud Dept. of Neurology University Hospital Basel Petersgraben 4 4031 Basel, Switzerland Tel.: +41-61/265-4151 Fax: +41-61/265-4100 E-Mail: mhardmeier@uhbs.ch

Acute infectious disorders of the spinal cord and its roots with gadolinium-DTPA enhancement in magnetic resonance imaging

We studied three patients with myelomeningoradiculitis caused byBorrelia burgdorferi, herpes zoster virus or cytomegalovirus infection. All patients underwent MRI of the spinal cord with gadolinium-DTPA and showed enhancing lesions of the spinal cord or nerve roots that correlated with clinical signs. Gadolinium-DTPA enhancement may visualize lesions that suggest an inflammation associated with blood-brain-barrier alteration and indicate the diagnosis before serological results are available.

Isolated bilateral abducent nerve palsy due to a spontaneous left–side dural carotid cavernous fistula Type Barrow C

Sirs: Carotid cavernous fistulas (CCFs) are commonly associated with congestive orbito-ocular features – in most cases ipsilateral to the fistula side [1, 2]. As a rare entity, we describe a case of isolated bilateral abducent nerve palsy due to a spontaneous left-side CCF, whose presence was proven by magnetic resonance (MR) digital subtraction angiography (DSA). A 63-year old woman developed acute horizontal diplopia associated with nausea, without preceding trauma or illness. The symptoms disappeared within a few hours, reappeared again 10 days later and persisted thereafter. Her medical history included an essential arterial hypertension. Physical examination showed a bilateral, left-dominant abducent nerve palsy and a pulsatile bruit over the left carotid arteries. On request the patient told us about an intermittent, pulsatile left-side tinnitus, which had started about 6 months prior to the occurrence of the diplopia. The funduscopic examination and the visual acuity were normal. Time-of-flight MR angiography of the cerebral vessels and color-coded Doppler sonography were normal. MR DSA [3] showed filling of the cavernous sinus during the early arterial phase (Fig. 1A), proving the presence of a CCF. A second more subtle finding – only detected after further analysis of the MR DSA images – was the presence of small flow voids adjacent to the cavernous segment of the internal carotid artery on T2-weighted MR images of the brain (Fig. 1B). On intra-arterial DSA the fistula was seen to be filled only by branches of the left maxillary artery (Fig. 1C). Cavernous outflow drained into the left superior ophthalmic vein, which showed a focal stenosis in its proximal segment, into the left middle cerebral vein and bilaterally into petrosal veins. The embolization with microparticles of the major feeding branches arising from the maxillary and the middle meningeal arteries resulted in a marked reduction of the fistula flow. A few hours after embolization the pulsatile tinnitus disappeared and within about 10 weeks the bilateral abducent nerve palsy gradually regressed. MR DSA 6 weeks after embolization showed signs of a slight persistent fistula, and intraarterial DSA 18 weeks after embolization disclosed a complete occlusion of the fistula. Our patient presented an isolated left-dominant bilateral abducent nerve palsy due to a spontaneous left-side dural CCF Type Barrow C [4]. Apart from the diplopia the only other clinical symptom was a left-side pulsatile tinnitus, which is a well-known feature of dural arteriovenous fistulas (DAVFs). Abducent nerve palsy is the most common cranial nerve palsy associated with CCF [2], but isolated bilateral abducent nerve palsy due to a unilateral CCF is a rare entity [5]. Isolated abducent nerve LETTER TO THE EDITORS

Fast-track versus long-term hospitalizations for patients with non-disabling acute ischaemic stroke

The aim was to assess the feasibility and safety of fast‐track hospitalizations in a selected cohort of patients with stroke.

Certification of stroke centre and stroke units in Switzerland

In Switzerland, since 2011, a mandatory certification system for stroke units (SUs) and stroke centres has been successfully implemented. Detailed criteria for stroke centres and SUs focusing on leadership, specialized staff, infrastructure, diagnostic procedures, treatment procedures, monitoring, education, research and key data have been defined by the Swiss Federation of Clinical Neurosocieties Swiss Stroke Committee mainly based on recommendations of the Swiss Stroke Society and European Stroke Organisation. During the certifications procedures, a very close and fruitful cooperation between stroke centres and SUs and other hospitals in regional networks could be observed. Improvement in the infrastructure and the quality of stroke care has been achieved during the last years.

Die neuen Antikoagulantien bei Hirnschlagpatienten

The Swiss Registry of New Anticoagulants in Stroke Patients (NOACISP): A national audit and prospective registry