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Intravenous thrombolysis (IVT) is the evidence-based treatment of acute ischemic stroke in the first 3 h after symptom onset (IVT 3-4.5 h: off-label use with informed consent of the patient). However, intra-arterial thrombolysis (IAT) results in higher recanalization rates of the middle cerebral artery compared to IVT. Therefore it seems reasonable to apply IAT in addition or instead of IVT up to 6 h after symptom onset.

Imaging has become increasingly important for diagnosis and treatment of disorders in neurology and neurosurgery. Often, however, physicians are uncertain which imaging modality to chose for diagnosis and which techniques can be used to help for treatment. To answer a specific question clinicians have to rely on history and clinical findings. According to a cardinal clinical symptom or sign the imaging technique with the highest sensitivity and specificity for the given problem is chosen. In this review imaging techniques for the most common cardinal symptoms and signs in neurology and neurosurgery which need imaging for management are discussed.

We report a case of a 52-year-old female patient with known cerebral cavernomas and acute headache. A cranial CT scan excluded an intracranial bleeding. Cavernomas are rare vascular malformations of the venous blood system (synon. cavernous angiomas) with a slow blood flow. Clinical manifestation is presented between an age of 30-50 years with mostly unspecific neurological symptoms like headache, nausea, vomiting and dizziness, but also epileptic seizures and bleedings may occur. In general, therapy is symptomatic. In cases of seizures, however, anticonvulsive treatment is indicated. Operation can be discussed for peripheral localized cavernomas with bleeding or for refractory seizures. If antiplatelet or anticoagulation therapy is necessary due to other diseases (coronary heart disease, atrial fibrillation, thrombosis, pulmonary embolism), cerebral cavernomas are not considered as an absolute contraindication. The risk for an ischemic stroke under atrial fibrillation (5-20%), for example, is higher than the risk for bleeding of a cerebral cavernoma under anticoagulation therapy.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. The inflammation causes focal demyelination and loss of axons, neurons and glial cells. Typical symptoms and signs are monocular blurred vision, double vision, sensory symptoms and motor weakness, and eventually also cognitive deficits and a disturbed micturition. In younger patients the neurological deficits tend to be present for a limited time and then to improve and disappear, only to be followed by new and different deficits later on. Each relapse may leave neurological deficits which in a later course tend to progress slowly, uninterrupted by remissions. When older patients present for the first time with MS, they tend to present with primary progressive spasticity. Important ancillary tests and findings to confirm the diagnosis are multiple focal lesions on MR images, oligoclonal bands in the cerebrospinal fluid, and slowed evoked potentials. Relapses are treated with corticosteroids. Immunomodulation with beta-interferons or glatiramer acetate reduce the number and severity of relapses and long-term disability. Very active forms can be treated with immunosuppression using mitoxantrone. Individual manifestations such as urinary tract infections or paroxysmal phenomena should be treated accordingly with medication.

Consciousness and wakefulness require normal functioning of the cerebral cortex, as well as of the midbrain reticular formation and its ascending projections. Bilateral structural lesions or functional disturbances of these brain areas can impair consciousness and can produce coma. The bodily posture and brainstem reflexes of the comatose patient provide clues as to whether the lesion lies in the brainstem or in the cerebral hemispheres. Brainstem reflexes are usually preserved in coma due to bilateral hemispheric dysfunction, including metabolic, anoxic, and toxic coma. Ancillary tests are used to answer specific diagnostic questions. The treatment of coma depends on its etiology.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF is 0.4% in the general population and increases with age up to 6-8% in octogenarians. In Switzerland, approximately 68,000 persons are in atrial fibrillation, and in the EU countries 3.5 millions. Atrial fibrillation disturbs synchronous mechanical atrial activity and impairs the haemodynamics. This can give rise to thrombus formation, mostly in the left atrial appendage, and embolism to the systemic circulation. Clinical manifestations are most often neurological such as transient ischaemic attacks or ischaemic strokes, on average 5% per year. Of all strokes, one in every six occurs in patients with AF. Antiarrhythmic therapy is useful to improve cardiac rate and function in AF. However, to reduce first or recurrent emboli, antithrombotic therapy is of paramount importance. Adjusted-dose warfarin reduces first or recurrent strokes by about 60%. When patients with non-valvular AF are anticoagulated, the odds against ischaemic stroke and intracranial bleeding favour an INR between 2.0 and 3.0. Acetylsalicylic acid is less efficacious than warfarin in AF patients, reducing the risk of stroke by about 20%. Therefore, anticoagulation is the current treatment modality in AF patients at high or intermediate risk, i.e. patients with history of transient ischaemic attack or stroke, those aged > 65 years, those with a history of hypertension, diabetes, heart failure or structural heart disease, valvular disease or significant systolic dysfunction. Antiplatelet agents should be used only for young (< 65 years) AF patients at low risk.

Vascular diseases including stroke increase with advancing age. Their occurrence reflects the lifestyle and eating habits of a society. In industrialized countries stroke causes a significant loss of DALYs. Each year, approximately 150 persons per 100,000 inhabitants suffer a stroke. Half a year after the stroke, two of three stroke victims are dead or dependent, and all stroke survivors are at risk to suffer recurrent strokes. Stroke is due to a focal ischemia. In the core of the ischemia blood flow is reduced substantially, mostly to a level below the infarction threshold. In the borderzone collaterals can still provide sufficient blood to preserve the neurons though the reduced blood flow does not suffice for neuronal functioning. This state below functional and above infarction threshold is called penumbra. When the stroke signs are recognized early and the occluded vessel is recanalized with thrombolytics or mechanically the brain tissue in the penumbra can be preserved and the fate of the stroke victim is improved compared to spontaneous course. Before administration of thrombolytics neurological examination and imaging of the brain using CT or MRI are necessary. After stroke, survivors will benefit significantly from secondary prevention. In order to perform an individually tailored prevention, additional investigations such as neurovascular and cardiac ultrasound, cardiac monitoring and blood examinations are necessary to define the cause of the stroke. In addition, recognition and modification of individual vascular risk factors are of paramount importance.

Aspirin is the drug of choice in most patients with acute stroke, if thrombolysis is contraindicated. Heparin is only used in acute stroke due to cerebral venous thrombosis, extracranial carotid or vertebral artery dissection and cardiac emboli with high risk of recurrence. In the prevention of recurrent stroke in patients with a noncardioembolic ischemic stroke antiplatelet agents are used. Aspirin is the first-line agent. Clopidogrel or a combination aspirin/dipyridamol are recommended for patients with several risk factors or recurrent cerebrovascular events. Warfarin has demonstrated a clear efficacy in stroke prevention in patients with atrial fibrillation, cerebral venous thrombosis and antiphospholipid antibody syndrome. Other, less well established possible indications for warfarin in the secondary prevention of stroke are symptomatic intracranial artery stenosis, large aortic atheroma, extracranial carotid or vertebral artery dissection and patent foramen ovale.

Randomised trials provide the best evidence on the effects of treatment on a particular disease. They can also provide valuable data on outcome. In the present article, data from 1631 Swiss patients randomised in the International Stroke Trial (IST) are presented. Baseline characteristics and outcome in the Swiss patients were compared with the 17,804 patients randomised in other countries. On average, compared with other countries, Swiss patients were: 2.5 years older (CI: 1.9-3.1; p < 0.001); more likely to have presented with total anterior circulation infarcts (28 vs 23%); less likely to have lacunar strokes (16 vs 25%; p < 0.00001); more likely to be randomised and treated early (within 3 hours, 7 vs 4%, and within 6 hours, 25 vs 15%; p < 0.00001). However, Swiss patients were more likely to be dead or dependent 6 months after the stroke (66.9 vs 62.2%; p < 0.00001). The difference in death or dependency was almost entirely explained by the difference in age and baseline severity of strokes. These data highlight the difficulties inherent in between-country comparisons of outcome after stroke. They also emphasise the need for international multicentre trials to use methods of randomisation (either stratification or minimisation), as IST did, to ensure balance of prognostic factors within each participating country; to do otherwise might confound the assessment of the effect of treatment.

This article reviews new drugs and recent knowledge or indications for old drugs for the treatment of neurological disorders. Drugs for disorders such as migraine, epilepsy, Parkinson's disease, Alzheimer's disease, ischemic stroke, amyotrophic lateral sclerosis and multiple sclerosis are considered.

Magnetic resonance imaging represents today the most important tool in neuroradiology for both clinical practice and research. MRI allows imaging of the human body in 2 or 3 dimensions with variable tissue contrast. The natural diffusion of tissue protons can now be used as a supplementary contrast mechanism. Different MRI techniques can be used to obtain clinically useful diffusion-weighted images. These techniques all require the use of strong gradient pulses in order to obtain the diffusion contrast. In the current article, the most important physical principles of diffusion measurement are presented. After a short introduction into the basic physical principles, we will present the prerequisites and limitations of clinically relevant applications today. Finally a few select examples of clinical use of these techniques in the acute diagnosis of stroke will be presented.

In the acute stage of stroke, fibrinolytics are beneficial for up to 3, and in some patients up to 6, hours. If fibrinolytics are contraindicated, aspirin should be given. Heparin is dangerous due to the threat of intra- and extracranial hemorrhage. For secondary prevention, anticoagulants are indicated. When hypercholesterolemia is present, statins should be given.

Two large randomized studies - NINDS and ECASS - have shown that fibrinolytics, when given early enough, reduce morbidity and mortality in acute stroke. The treatment has to be initiated within three hours after onset of symptoms. In middle cerebral artery stroke, fibrinolysis can be performed within six hours from onset, guided by computed tomography criteria. Thereafter, s.c. low-molecular-weight heparin can still improve the fate of the patient. Currently, the potential benefit or harm of unfractionated heparin and aspirin is not yet known. However, large-scale studies using standard heparin, aspirin of low-molecular-weight heparin are in progress with results expected soon. After the acute stage of stroke, risk factors have to be eliminated or modified, and anticoagulants, platelet inhibitors and, in selected cases, carotid endarterectomy are useful in preventing recurrent stroke or other vascular events.

The outcome of stroke improves significantly, when recognized and treated within 3 hours and in certain cases not later than 6 hours. In addition, secondary preventive measures potentially ameliorate the fate of the patient as well, especially when the cause of stroke is known. In this first article we outline the practical diagnosis and evaluation of stroke, both in the acute stage and thereafter. The differential diagnosis is also considered.

Unlabelled: Transcranial color-coded duplex sonography (TCCD) represents an improvement in ultrasound technology for study of the intracranial circulation. This new method was applied in 33 healthy volunteers and 63 neurological patients in order to study the following questions: (1.) how often can non-occluded intracranial arteries be delineated; (2.) reliability of pathological TCCD findings in comparison with cerebral angiography; (3.) reference blood flow velocity data., Results: 99% of vertebral (VA), 98% of basilar (BA), 96% of middle (MCA) and posterior cerebral (PCA), 95% of internal carotid (ICA; siphon and terminal segment), 93% of anterior cerebral (ACA), and 86% of posterior inferior cerebellar (PICA) arteries were delineated. In conjunction with the findings of extracranial color-coded duplex sonography (ECCD), 4 stenoses (2 MCA, 1 ICA and PCA each), 8 occlusions (4 ICA, 1 ACA, MCA, BA and VA each; differential diagnosis: subtotal stenosis), 9 collateral circulations (anterior and posterior communicating arteries in 4 cases each, occipital artery-intracranial VA in one), 4 cerebral arteriovenous malformations, and 2 giant aneurysms of the terminal ICA were suspected and confirmed by angiography. However, 2 hypoplastic VA's and ipsilateral PICA's were missed. (3.) Maximal +/- SD values were 83 +/- 27, 110 +/- 18, 67 +/- 12, 64 +/- 13, 53 +/- 13, and 51 +/- 12 cm/sec for systolic, and 36 +/- 9, 49 +/- 9, 30 +/- 7, 29 +/- 8, 24 +/- 7, and 25 +/- 7 cm/sec for end-diastolic velocity in the ACA, MCA, PCA, BA, VA, and PICA.

Strokes are classified according to their time course, involved vascular territory and etiology. For this purpose the important clinical symptoms and signs are reviewed and a rational use of the diagnostic tools is suggested. Mostly depending on the etiology of a stroke, decisions for treatment and prophylaxis are made. Treatment consists in general medical management and in most cases use of anticoagulants and aspirin, which have proved efficacious in prevention of recurrent stroke. Two studies have also proved the prophylactic value of carotid endarterectomy after stroke.

Aortic diseases in particular aneurysms may be accompanied by spinal ischemia occurring either spontaneously or as complications of surgical interventions. Surgery of the abdominal or thoraco-abdominal aorta is followed in 5 to 15% by ischemia of the spinal cord, in exclusively abdominal interventions in 1.5%. Clinical manifestation depends largely on anatomy of the spinal vessels. If complete transverse myelopathy does not occur, presentation as anterior or posterior arterial ischemic syndrome is common. Other forms of myelopathy are rare. Perfusion deficits through intercostal and lumbar arteries are important in pathogenesis. The great radicular artery is particularly important. Ischemia occurs after hypotensive episodes (ruptured aneurysm) intraoperative clamping of the suprarenal aorta or by occlusion (thrombotic, arterio-arterial embolism). Careful surgical techniques are important for prevention of these neurologic complications. Possibilities for treatment and chances for spontaneous recovery of established spinal-cord lesions are poor.

In only a few years magnetic resonance angiography has evolved to a clinically useful tool. In many situations it can resolve questions which used to be addressed by conventional contrast angiography, such as carotid stenoses, aneurysms, arteriovenous malformations, and venous and sinus disorders. In addition, selective magnetic resonance angiography provides information on direction and origin of flow and circulation in vessels serving as collaterals.

MR angiography (MRA) combined with selective saturation techniques has proved to be a reliable method for the determination of flow direction and vascular supply at the level of the circle of Willis. We describe its application to the vertebrobasilar system (VBS) in ten volunteers and five patients with abnormal findings. In one patient with postsurgical stenosis of the brachiocephalic artery, reverse flow of the vertebral artery (VA) was demonstrated. Collateral blood flow from the anterior circulation over the posterior communicating arteries was shown in three patients with bilateral vertebral or proximal basilar artery occlusion. Due to increase of pressure during contrast injection into the contralateral VA, DSA showed reverse flow of a dissected VA in one patient. MR flow determination as well as TCD proved antegrade flow. All results correlated with both DSA and transcranial Doppler (TCD). The technique is little time consuming and is a promising add-on examination to conventional and MRA imaging of the VBS.

A Turbo FLASH sequence consisting of an initial non-selective 180 degree inversion pulse followed by an ultrafast FLASH sequence with very short repetition and echo times (TR = 7 ms, TE = 4 ms) was used to study 20 patients with focal liver lesions. The results were compared to T1-weighted gradient-echo (108/5/80 for TR/TE/flip angle) and T2-weighted spin-echo sequences (TR/TE/excitations = 2500 ms/40 ms, 90 ms, 140 ms/2). Liver-spleen contrast of the fast scans was superior to T1- and T2-weighted images for TI = 300 ms (0.59 +/- 0.12 vs 0.33 +/- 0.07 and 0.42 +/- 0.14 respectively). Liver-lesion contrast of the fast scans for TI = 300-700 ms was superior to the T1-weighted gradient echo sequence (0.49 +/- 0.21 vs 0.23 +/- 0.09), equal to the T2-weighted spin echo sequence for TE = 90 ms (0.54 +/- 0.17) but inferior to the 140 ms echo (0.63 +/- 0.18). On Turbo FLASH scans, there were no flow or motion artifacts and lesions borders and structures were better delineated than on the spin-echo images. Imaging time for the whole liver is less than a minute.