[Online survey of the organizational structures of emergency neurology in Germany]. / Onlineumfrage zur Struktur der Notfallneurologie in Deutschland 2016.

In 2007, the first poll among neurologists provided some insight into the organizational structures of emergency neurology in Germany. Given that emergency neurology as well as emergency medicine in general have undergone substantial changes during the last decade, the subcommittee Neurological Emergency Medicine of the German Neurological Society conducted a follow-up study to explore current structures supporting neurological emergency medicine in German neurological hospitals. Between July and September 2016, an online questionnaire was e­mailed to 675 neurologists in institutions participating in in-patient neurological care. Of these, some 32% (university hospitals 49%) answered. Neurological patients represent 12-16% and hence a significant proportion of emergency patients. The fraction of in-patients admitted to hospitals via emergency departments amounted to 78% (median) in general hospitals and 52% in university hospitals. Most emergency departments are organized as an interdisciplinary structure combining conservative with surgical disciplines frequently led by an independent department head. Neurology departments employ rather diverse strategies to organize neurological emergency care. Also, the way emergency patients are assigned to different disciplines varied largely. Currently, neurological patients represent a rather growing fraction of patients in emergency departments. An increasing proportion of neurology in-patients enter the hospital via emergency departments. Neurology departments in Germany face increasing challenges to cope with large numbers of neurological emergency patients. While most of the participating neurologists indicated suffering predominantly from scarce personal resources both in neurology and neuroradiology, an independent neurological emergency department was not considered an option.

[The course of early neurological rehabilitation in a patient with severe posterior reversible encephalopathy syndrome]. / Verlauf der neurologischen Frührehabilitation bei einem Patienten mit ausgeprägtem Posteriorem Reversiblem Enzephalopathiesyndrom.

Posterior reversible encephalopathy syndrome (PRES) is widely held to be a benign and potentially reversible disease. However, severe cases have been described in the literature. Data on the long-term outcome of these severe cases are scarce. Furthermore, there are no data focusing on potential benefits of neurological early rehabilitation in these patients. Here we present the clinical picture, neuroimaging features, rehabilitative course and long-term outcome of a patient with severe PRES who underwent early neurological rehabilitation.

Time-of-flight angiography: a viable alternative to contrast-enhanced MR angiography and fat-suppressed T1w images for the diagnosis of cervical artery dissection?

OBJECTIVES: To compare the use of an unenhanced high-resolution time-of-flight MR angiography sequence (Hr-TOF MRA) with fat-suppressed axial/coronal T1-weighted images and contrast-enhanced angiography (standard MRI) for the diagnosis of cervical artery dissection (cDISS). METHODS: Twenty consecutive patients (9 women, 11 men, aged 24-66 years) with proven cDISS on standard MRI underwent Hr-TOF MRA at 3.0 T using dedicated surface coils. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV), Cohen's kappa (к) and accuracy of Hr-TOF MRA were calculated using the standard protocol as the gold standard. Image quality and diagnostic confidence were assessed on a four-point scale. RESULTS: Image quality was rated better for standard MRI (P = 0.02), whereas diagnostic confidence did not differ significantly (P = 0.27). There was good agreement between Hr-TOF images and the standard protocol for the presence/absence of cDISS, with к = 0.95 for reader 1 and к = 0.89 for reader 2 (P < 0.001). This resulted in SE, SP, PPV, NPV and accuracy of 97 %, 98 %, 97 %, 98 % and 97 % for reader 1 and 93 %, 96 %, 93 %, 96 % and 95 % for reader 2. CONCLUSIONS: Hr-TOF MRA can be used to diagnose cDISS with excellent agreement compared with the standard protocol. This might be useful in patients with renal insufficiency or if contrast-enhanced MR angiography is of insufficient image quality. KEY POINTS: • New magnetic resonance angiography sequences are increasingly used for vertebral artery assessment. • A high-resolution time-of-flight sequence allows the diagnosis of cervical artery dissection. • This technique allows the diagnosis without intravenous contrast medium. • It could help in renal insufficiency or when contrast-enhanced MRA fails.

[Current registry studies of acute ischemic stroke]. / Aktuelle Registerstudien beim akuten ischämischen Schlaganfall.

Study registries offer the opportunity to evaluate the effects of new therapies or to observe the consequences of new treatments in clinical practice. The SITS-MOST registry confirmed the validity of findings from randomized trials on intravenous thrombolysis concerning safety and efficacy in the clinical routine. Current study registries concerning new interventional thrombectomy techniques suggest a high recanalization rate; however, the clinical benefit can only be evaluated in randomized, controlled trials. Similarly, the experiences of the BASICS registry on basilar artery occlusion have led to the initiation of a controlled trial. The benefit of hemicraniectomy in malignant middle cerebral artery infarction has been demonstrated by the pooled analysis of three randomized trials. Numerous relevant aspects are currently documented in the DESTINY-R registry. Finally, the recently started RASUNOA registry examines diagnostic and therapeutic aspects of ischemic and hemorrhagic stroke occurring during therapy with new oral anticoagulants.

Intra-arterial application of nimodipine in reversible cerebral vasoconstriction syndrome: a diagnostic tool in select cases?

INTRODUCTION: Differential diagnoses of the reversible cerebral vasoconstriction syndrome (RCVS) include all forms of intracranial stenotic disease, such as primary or secondary vasculitis of the central nervous system. Here, we tested the hypothesis that angiographic response to intra-arterial nimodipine application may be helpful in differentiating between RCVS and other entities. METHODS: A digital subtraction angiographic (DSA) series of nine consecutive patients with suspected RCVS that were treated by intra-arterial nimodipine due to clinical worsening were retrospectively analyzed. Pre- and post-therapeutic DSA findings of patients with later-confirmed RCVS were compared to those in which another diagnosis was finally made. RESULTS: Intra-arterial nimodipine resulted in a normalization of both the diameter of the main trunks of the cerebral vessels and the caliber of the peripheral vessels in all RCVS patients. This was not the case in the non-RCVS patients, in whom only a slight general vasodilatation was observed. DISCUSSION: Our preliminary results indicate that angiographic response to intra-arterial application might be a helpful differential diagnostic tool in select patients with suspected RCVS.

Polyneuropathy associated with cholesterol crystal embolism.

INTRODUCTION: Cholesterol crystal embolism complicating arterial catheterization usually presents as a multiorgan disease with renal failure, abdominal problems, and skin manifestations. METHODS: We present a patient with hypertension and generalized arteriosclerosis who presented with muscle weakness, diffuse pain in the extremities, and renal failure 3 weeks after coronary catheterization and angioplasty of the right coronary artery. Muscle weakness progressed during the following months. RESULTS: Nerve conduction studies and nerve biopsy showed severe axonal nerve injury. Biopsy of the kidney revealed the diagnosis of cholesterol crystal embolism. CONCLUSION: The clinical presentation indicates a direct association of cholesterol crystal embolism and polyneuropathy. Although cholesterol crystal embolism represents a rare cause of polyneuropathy, it should be considered in patients with acute onset polyneuropathy and sudden onset multiorgan disease after arterial catheterization.

[New aspects of MRI for diagnostics of large vessel vasculitis and primary angiitis of the central nervous system]. / Neue Aspekte der MRT-Bildgebung zur Diagnostik der Großgefäßvaskulitiden sowie der primären Angiitis des zentralen Nervensystems.

Vasculitis is a rare disease and clinical symptoms are often unspecific. Accurate and early diagnosis is mandatory in order to prevent complications, such as loss of vision or stroke. Imaging techniques can contribute to establishing a definite diagnosis and to evaluate disease activity and the extent of the disease in various vascular regions. Conventional imaging methods, such as computed tomography (CT) and magnetic resonance (MR) angiography, as well as digital subtraction angiography allow the vessel lumen but not the vessel wall to be depicted. However, vasculitis is a disease which primarily affects the vessel wall, therefore conventional imaging modalities often fail to make a definite diagnosis. Recently black-blood high resolution MR in vivo imaging has been used to visualize cervical and intracranial vasculitis. This review article presents imaging protocols for intracranial and cervical black-blood MR imaging and clinical cases with large vessel vasculitis and vasculitis of the central nervous system. Furthermore the current literature, examples of the most common differential diagnoses of cervical and cranial arteriopathy and the potential of other imaging modalities, such as PET/CT and ultrasound will be discussed.

Mimicking of cerebral herniation through gamma-hydroxybutyric acid therapy.

Besides being a treatment option for narcolepsy, gamma-hydroxybutyrate is used as an adjuvant during anesthesia in Europe. In addition, it is illegally used as a recreational drug. Fixed and dilated, asymmetric pupils developed in 2 patients during continuous therapy with intravenous gamma-hydroxybutyrate, which was added to the long-term anesthetics fentanyl and midazolam. Cerebral herniation as an alternative cause for the pupillary changes was ruled out by using continuous intracranial pressure monitoring and computed tomography. In both patients, the pupillary abnormalities resolved after discontinuation of gamma-hydroxybutyrate. Thus, fixed and dilated pupils that are asymmetric seem to be an important side effect of gamma-hydroxybutyrate therapy that may mimic cerebral herniation in deeply anesthetized patients.

Reduced cerebrovascular CO(2) reactivity in CADASIL: A transcranial Doppler sonography study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography. METHODS: Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO(2) reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0+/-2.4 years) and an equal number of age- and sex-matched control subjects. RESULTS: Compared with control subjects, CO(2) reactivity was reduced in CADASIL (33.4+/-2.7% versus 45.3+/-3.0%; P:<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P:<0.05). CO(2) reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5+/-2.7% versus 36.8+/-3.4%; P:<0.05). MCA MFV was reduced in CADASIL (45.6+/-2.2 cm/s versus 54.2+/-2.4 cm/s; P:<0.05) and correlated negatively with age both in affected individuals (r=-0.314; P:<0.05) and control subjects (r=-0.339; P:<0.05). Resistance index was not significantly altered (59.0+/-1.0% versus 57.7+/-1.2%; P:=0.42). CONCLUSIONS: In CADASIL, there is a reduction of both CO(2) reactivity and basal MCA MFV. The reduced CO(2) reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO(2) reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

Plasminogen activation in focal cerebral ischemia and reperfusion.

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2%+/-8.5% and 19.4%+/-30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8%+/-42.2%, P < 0.05) but not in the cortex (43.0%+/-34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury (r = 0.873, P < 0.001). No such correlation was found in the cortex (r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.

Increased intracellular calpain detection in experimental focal cerebral ischemia.

Calpains are intracellular proteinases whose proteolytic activity is directed mainly against the cytoskeleton and regulatory proteins. We studied the presence of calpain by immunohistochemistry in a rat model of reversible focal cerebral ischemia (3 h) at various times of reperfusion. The numbers of calpain-positive cells on the ischemic side were compared with the non-ischemic side. In controls only 2 +/- 1% cells were positive, whereas the cortex of the ischemic vs the non-ischemic side showed 88 +/- 3% vs 13 +/- 4% calpain-positive cells (p < 0.001), and the basal ganglia 47 +/- 3% vs 13 +/- 4% (p < 0.01) after 3 h ischemia and 24 h reperfusion. This is the first demonstration of elevated intracellular levels of calpains in areas of cerebral ischemia. Longer reperfusion resulted in an increase in calpain positivity.

Plasminogen activation in experimental permanent focal cerebral ischemia.

BACKGROUND: Previous experimental work using in situ zymography has shown very early increased plasminogen activation in ischemic regions after 3 h of ischemia with and without reperfusion. The objective of the present study was to evaluate the time course and extent of plasminogen activation in long-term permanent focal cerebral ischemia. MATERIAL AND METHODS: The middle cerebral artery in male Fisher rats was irreversibly occluded by electrocoagulation. Duration of ischemia was 48, 72, and 168 h. Occlusion was controlled in vivo by MRI at day 2. Plasminogen activation was detected by in situ zymography of 10 microm cryosections with an overlay containing plasminogen and the plasmin substrate caseine. Areas of plasminogen activation were compared to structural lesions (immunohistochemical loss of microtubule-associated protein 2; MAP 2). RESULTS: Compared to controls, increased plasminogen activation was observed in the basal ganglia and the cortex of the ischemic hemisphere after 48, 72, and 168 h (affected area of basal ganglia: 44.5+/-21.9, 70.1+/-2.3 and 66.6+/-2.8%, respectively; affected area of cortex: 63.4+/-9.8, 67.7+/-0.7 and 64.0+/-3.7%, respectively). The duration of ischemia had no significant influence on the extent of plasminogen activation. Areas of increased plasminogen activation significantly overlapped with and exceeded areas of MAP 2 loss (P<0.005). DISCUSSION: Permanent focal cerebral ischemia leads to increased plasminogen activation in ischemic regions. This plasminogen activation remains elevated at persistent levels over days. It may contribute to extracellular matrix (ECM) disruption, secondary hemorrhage, and brain edema in subacute stages of ischemic stroke.

Contralateral cerebral blood flow velocity changes after intracarotid amobarbital injection.

BACKGROUND AND PURPOSE: The intracarotid amobarbital procedure (IAP) leads to a prompt decrease in ipsilateral middle cerebral artery (MCA) mean blood flow velocity (MFV). Little is known about contralateral MFV changes. METHODS: The authors investigated bilateral MCA MFV using transcranial Doppler sonography (TCD) in 8 patients with epilepsy undergoing IAP. Measurements were excluded from analysis if angiography revealed any signs of interhemispheric cross-flow. RESULTS: With in 64 seconds after amobarbital injection, ipsilateral MFV decreased to a mean of 44.4% +/- 7.5% of baseline value (P < .01). In the absence of interhemispheric cross-flow and within 68 seconds, contralateral MFV decreased to 83.1% +/- 7.9% (P < .01). CONCLUSIONS: The observed decrease of contralateral MFV was not caused by amobarbital cross-perfusion. A possible underlying mechanism may be interhemispheric deafferentation.

Heparin-mediated extracorporeal LDL/fibrinogen precipitation--H.E.L.P.--in coronary and cerebral ischemia.

Cerebral and myocardial infarctions share common aspects of pathobiochemistry. The central problem is the oxygen supply of the infarcted region. To maintain this supply, H.E.L.P.-apheresis (Heparin-mediated Extracorporeal LDL/Fibrinogen Precipitation) has already proven beneficial in the prevention and therapy of myocardial infarction. Since H.E.L.P.-apheresis can lower significantly plasma viscosity and erythrocyte aggregation without reducing the oxygen transport capacity, patients with cerebral infarction (stroke) may also benefit from our experiences in myocardial ischemia. The system is designed to remove selectively plasma fibrinogen, LDL-cholesterol and lipoprotein(a) from blood circulation, simultaneously. The removal of the plasma compounds is achieved by extracorporeal precipitation with heparin at low pH. Excess heparin is completely removed by an adsorber before the plasma is given back to the patient. H.E.L.P.-apheresis has proved to be safe in patients with coronary heart disease and allows a controlled reduction of thrombogenic plasma compounds. It is therefore hoped to be effective also in patients with acute ischemic stroke.

Hyperattenuated intracerebral lesions after mechanical recanalization in acute stroke.

BACKGROUND AND PURPOSE: Following mechanical recanalization of an acute intracranial vessel occlusion, hyperattenuated lesions are frequently found on postinterventional cranial CT. They represent either blood or-more frequently-enhancement of contrast agent. Here, we aimed to evaluate the prognostic value of these hyperattenuated intracerebral lesions. MATERIALS AND METHODS: One hundred one consecutive patients with acute stroke in the anterior circulation who underwent mechanical recanalization were included. Risk factors for hyperattenuated intracerebral lesions were assessed, and lesion volume was compared with the volume of final infarction. Clinical outcome and relative risk of secondary hemorrhage were determined in patients with and without any hyperattenuated lesions and compared. RESULTS: The frequency of hyperattenuated lesions was 84.2%. Risk factors for hyperattenuated lesions were female sex, higher NIHSS score on admission, and higher amount of contrast agent applied. On follow-up, 3 patients showed no infarction; 53 patients, an ischemic infarction; and 45 patients, a hemorrhagic infarction. In all except 1 case, final volume of infarction (median = 92.4 mL) exceeded the volume of hyperattenuated intracerebral lesions (median = 5.6 mL). Patients with hyperattenuated lesions were at a 4 times higher relative risk for hemorrhagic transformation but had no significantly worse clinical outcome. CONCLUSIONS: Our data show that the extent of postinterventional hyperattenuated intracerebral lesions underestimates the volume of final infarction. Although hyperattenuated lesions indicate a higher risk of secondary hemorrhagic transformation, their presence seems not to be of any prognostic value regarding clinical outcome.

The crossed leg sign indicates a favorable outcome after severe stroke.

OBJECTIVE: We investigated whether crossed legs are a prognostic marker in patients with severe stroke. METHODS: In this controlled prospective observational study, we observed patients with severe stroke who crossed their legs during their hospital stay and matched them with randomly selected severe stroke patients who did not cross their legs. The patients were evaluated upon admission, on the day of leg crossing, upon discharge, and at 1 year after discharge. The Glasgow Coma Scale, the NIH Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI) were obtained. RESULTS: Patients who crossed their legs (n = 34) and matched controls (n = 34) did not differ in any scale upon admission. At the time of discharge, the GCS did not differ, but the NIHSS was better in crossed legs patients (6.5 vs 10.6; p = 0.0026), as was the mRS (3.4 vs 5.1, p < 0.001), and the BI (34.0 vs 21.1; p = 0.0073). At 1-year follow-up, mRS (2.9 vs 5.1, p < 0.001) and the BI (71.3 vs 49.2; p = 0.045) were also better in the crossed leg group. The mortality between the groups differed grossly; only 1 patient died in the crossing group compared to 18 in the noncrossing group (p < 0.001). CONCLUSION: Leg crossing is an easily obtained clinical sign and is independent of additional technical examinations. Leg crossing within the first 15 days after severe stroke indicates a favorable outcome which includes less neurologic deficits, better independence in daily life, and lower rates of death.

Progressive encephalomyelitis with rigidity and myoclonus preceding otherwise asymptomatic Hodgkin's lymphoma.

Stiff-person syndrome (SPS), a rare neuroimmunological disorder, is characterized by symmetrical rigidity and muscle stiffness, particularly of axial and proximal limb muscles. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a variant of SPS which includes additional clinical features (e.g. sensory symptoms, brain stem signs and pathological CSF findings). An association of both SPS and PERM with (solid) malignancies has been previously reported. Beyond this, there have been single reports of SPS in the setting of Hodgkin's lymphoma (HL). Here, we present a case of PERM associated with HL, with PERM preceding occurrence of lymphoma by more than seven months. Our observation has obvious implications for the management and, in particular, diagnostic evaluation of patients with PERM.