Diffusion tensor pyramidal tractography in patients with anterior choroidal artery infarcts.

BACKGROUND AND PURPOSE: Anterior choroidal artery (AchoA) stroke often evolves into undulating hemipareses, which sometimes progress to high-grade hemiparesis or hemiplegia but may also completely regress. Spatial relationships of AchoA infarcts to corticospinal tracts (CSTs) and CST integrity were investigated with diffusion tensor imaging (DTI) to identify prognostic parameters related to diffusion anisotropy changes in AchoA stroke. MATERIALS AND METHODS: Twenty-five AchoA stroke patients were prospectively examined with 3T DTI and diffusion tensor tractography (DTT) within a 3-day mean interval after onset. Analysis included the following: 1) stroke size on diffusion-weighted imaging; 2) fractional anisotropy (FA) and apparent diffusion coefficients at the largest stroke extents versus contralateral homologous structures; 3) lesion location related to CST ("involvement"); 4) amount of fiber trajectories of affected versus nonaffected CST ("fiber ratio"); and 5) presence of ipsilateral fiber disruption. Imaging findings were related to clinical status 3 months after symptom onset with respect to favorable, moderate, or unfavorable motor outcome. RESULTS: FA differences (due to FA reduction in the affected versus nonaffected hemisphere) were significantly higher for patients with unfavorable outcome (P=.03). Patients with favorable outcome had nearly symmetrical FA. CSTs were involved in ischemic lesions in all but 2 patients (complete involvement, n=3; partial, n=20). Two CSTs were completely disrupted, and both patients were hemiplegic (no disruption, n=14; partial disruption, n=9). Fiber disruption and CST involvement correlated negatively with motor score after AchoA stroke (P < .01), whereas infarct size did not. CONCLUSION: DTT may explain resulting motor dysfunction in patients with AchoA infarcts with more notably decreased FA being an indicator for unfavorable outcome.

[Duplex ultrasound of external carotid artery branches for the detection of dural arteriovenous fistulae]. / Duplexsonographie von A.-carotis-externa-Asten zum Nachweis duraler AV-Fisteln.

PURPOSE: To evaluate duplex ultrasonography of external carotid artery branches for the non-invasive diagnosis of dural AV fistulae (DAVFs). MATERIALS AND METHODS: A total of 126 patients suffering from pulsatile tinnitus underwent duplex ultrasonography of the cervicocephalic vasculature including external carotid artery branches. DAVFs were identified by increased flow velocity and reduced pulsatility. Patients with ultrasound findings of DAVFs were considered for selective angiography. RESULTS: Of the 23 patients that fulfilled the ultrasound criteria of AV fistula, 5 did not undergo angiography and were excluded from the study. The ultrasound findings of AV fistula were confirmed in all remaining patients (17 DAVFs, 1 extracranial AV fistula). Duplex ultrasound detected a DAVF of the common carotid artery in 29 %, of the external carotid artery in 65 % and of the external carotid artery branches in 100 % of the cases. CONCLUSION: Duplex ultrasonography of external carotid artery branches improves the non-invasive detection of DAVFs. For the evaluation of the venous drainage, however, selective angiography is necessary.

Clinical applications of MAO-inhibitors.

Monoamine oxidase inhibitors (MAO-I) have been useful in the treatment of both psychiatric and neurological disorders over centuries. Here we focus on the development of this drug treatment. Focus is given on the use of irreversible MAO-I's as well as on reversible ones. Benefit and side effects are reported for Parkinson's disease, Alzheimer's dementia, depression syndrome and panic disorders. The preclinical and clinical effects of selegiline with regard to neuroprotection are highlightened and the conclusion is drawn that there is good evidence for a clinical neuroprotective capacity based on the assumption that the 50 percent recovery of MAO-B is obtained already after a 10 days withdrawal of selegiline. There is also a focus on selegilines metabolism to amphetamine and metamphetamine. In order to avoid any such effects of metabolic compounds on the cardiovascular system Zydis Selegiline, a melt-tablet avoid of major metabolism to amphetamine and metamphetamine is described in detail. Developments in MAO-I research are discussed in detail as there are moclobemide, lacabemide, rasagiline. Interactions of MAO-I' with tricyclics and serotonin selective reuptake inhibitors (SSRI's) are described as there is mentioning of interactions of MAO-I's with other compounds in general. Tables and figures report on clinical studies and on pharmacological properties of MAO-I's.

[Factors influencing duration of hospitalization after stroke in Germany]. / Einflussfaktoren auf die stationäre Liegezeit nach Schlaganfall in Deutschland.

BACKGROUND: In Germany up-to-date data within community settings about factors influencing length of stay in acute hospitals are lacking. We, therefore, identified predictors for length of stay in acute hospital after ischemic stroke in a pooled analysis of large German stroke registers. METHODS: Ischemic stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000 and December 31, 2000 were analysed. The influence of patients' demographic and clinical characteristics as well as the characteristics of the treating hospitals on length of stay were analysed by multivariate linear regression. RESULTS: Overall, 13 440 patients after ischemic stroke were included in the analyses. Their mean age was 70 years, 53 % were men. Median length of stay in acute hospitals was 12 days. In multivariate analyses younger age, an increasing number of co-morbidities, and an increasing number of neurological deficits were identified as predictors of prolonged stay in hospital. Patients were more likely to stay longer in an acute hospital if they were to be discharged to a rehabilitation unit or to a nursing home. Length of stay was independently decreased for patients treated in hospitals providing acute stroke unit services and for hospitals treating more than 250 stroke patients per year. CONCLUSION: In addition to patients' demographic and clinical characteristics, length of stay in hospital was influenced by the hospitals' characteristics. Especially the volume of treated patients and the organisation of services within the hospital may play the key role.

Restless legs syndrome--new insights into clinical characteristics, pathophysiology, and treatment options.

We summarize recent advances in the clinical definition of restless legs syndrome (RLS), in understanding the basic mechanisms, and the successful treatments of RLS. New diagnostic instruments and severity scales have been developed for better phenotyping of the individual patient. Iron metabolism related components and the dopaminergic system have been extensively investigated in respect to the pathophysiology of RLS. The presence of mechanical hyperalgesia to pin-prick points towards an involvement of the nociceptive system. Genetic research has reported loci on chromosome 12q and 14q to play a role in the vulnerability to RLS. Placebo-controlled large-scale phase II and III treatment trials have shown that dopamine agonists are safe and efficacious agents for the treatment of this disorder.

Serotonin neurotoxins--past and present.

Autoxidation pathways and redox reactions of dihydroxytryptamines (5,6- and 5,7-DHT) and of 6-hydroxydopamine (6-OH-DA) are illustrated, and their potential role in aminergic neurotoxicity is discussed. It is proposed that certain aspects of the cytotoxicity of 6-OH-DA and of the DHTs, namely redox cycling of their quinone- and quinoneimine-intermediates as a source of free radicals, may also apply to quinoidal reactive intermediates and to glutathionyl- or cysteinyl conjugates ("thioether adducts") of o-dihydroxylated (catechol-like) metabolites of certain substituted amphetamines (of methylenedioxymethamphetamine (MDMA) and of methylenedioxyamphetamine (MDA)). Despite similarities in their primary interaction with the plasmalemmal (serotonergic transporter/dopamine transporter, SERT/DAT) and vesicular monoamine transporters (VMAT2), MDMA and fenfluramine (N-ethyl-meta-trifluoromethamphetamine, Fen) differ substantially in many aspects of their metabolism, pharmacokinetics, pharmacology, and neurotoxicology profile; the consequences of these differences for neuronal response patterns and long-term survival prospects are not yet fully understood. However, sustained hyperthermia appears to be a critical factor in these differences. Methodological requirements for adequate detection and description of pre- and postsynaptic forms of drug-induced neurotoxicity are exemplified using recently published accounts. The inclusion of microglial markers into research strategies has widened contemporary pathogenetic concepts on methamphetamine (MA)-induced neurotoxicity as an example of inflammatory neurodegeneration, thus complementing the traditional ROS and RNS-dependent stress models. Amphetamine-type neurotoxicity studies may assist in elaborating of preventive strategies for human neurodegenerative disorders.

[Quantifying stenosis of the internal carotid artery: which ultrasound criteria are relevant?]. / Quantifizierung von A. carotis interna-Stenosen: Welche Ultraschallkriterien sind geeignet?

UNLABELLED: Therapeutic decisions in cases of arteriosclerotic stenosis of the internal carotid artery usually depend mainly on the degree of stenosis. However, the recommendations with regard to suitable ultrasonographic criteria are so controversial that even authors of repute describe "confusion" and "chaos in methodology". AIM: The aim of this study is to assess which of the most frequently recommended sonographic criteria for stenosis best fulfill the requirements of an exact quantification of stenoses of the internal carotid artery. METHOD: In 42 consecutive cases the preoperative ultrasound findings were compared with the degree of stenosis in surgically removed specimens. The sonographic technique employed consisted of the analysis of 2 direct and 3 indirect hemodynamic criteria of stenosis. In 34 of these cases planimetry was performed, too. The specimens were obtained by eversion thrombendarteriectomy or arteriotomy; for determination of the degree of stenosis a Paladur molded cylinder was prepared and measured. RESULTS: Quantification of the haemodynamic criteria carries provided well with the endarterectomy specimens. Only in two cases there was a deviation of more than 10 %; however, in these two cases a change with time in the degree of stenosis was probably responsible for the discrepancy. In contrast, planimetry usually underestimated the degree of stenosis: In 61 % of the findings the ultrasonographic results differed by more than 10 % from the reference standard. CONCLUSION: Quantification of stenosis of the internal carotid artery should be made using a combination of direct and indirect haemodynamic ultrasonographic criteria.

Differential diagnosis of parkinsonian syndromes: dynamics of time courses are essential.

Differential diagnosis of parkinsonian syndromes encloses idiopathic Parkinson's disease, other primary neurodegenerative diseases (atypical parkinsonism), symptomatic cases, pseudoparkinsonism and inherited forms. Clinical diagnostic criteria are not safe when applied only at disease onset. Diagnostic accuracy can be intensified by recognition of distinct patterns of signs and symptoms and by focussing attention on the time course of the disease.

Which factors influence therapeutic decisions in Parkinson's disease?

Development of dyskinesia is a common phenomenon during the long-term course of Parkinson's disease. During the last few years, some but not all pathogenetic mechanisms causing dyskinesias in PD have become better understood. Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors. Most concepts underline the significance of pulsatile D1-receptor stimulation for the development of dyskinesias. The interactions between D1- and D2-mediated STR-Gpi pathways and colocalized neuropeptides are important but not fully understood. Glutamatergic overactivity might also be a significant pathogenetic factor. According to these pathophysiological concepts, therapeutic strategies focus mainly on continuous postsynaptic DA-receptor stimulation by long-acting DA-agonists or highly selective D2-agonists. Another strategy is the use of NMDA antagonists.

Molecular genetic alterations on chromosomes 11 and 22 in ependymomas.

Ependymomas arise from the ependymal cells at different locations throughout the brain and spinal cord. These tumors have a broad age distribution with a range from less than 1 year to more than 80 years. In some intramedullary spinal ependymomas, mutations in the neurofibromatosis 2 (NF2) gene and loss of heterozygosity (LOH) on chromosome arm 22q have been described. Cytogenetic studies have also identified alterations involving chromosome arm 11q, including rearrangements at 11q13, in ependymomas. We analyzed 21 intramedullary spinal, 14 ventricular, 11 filum terminale and 6 intracerebral ependymomas for mutations in the MEN1 gene, which is located at 11q13, and mutations in the NF2 gene, which is located at 22q12, as well as for LOH on 11q and 22q. NF2 mutations were found in 6 tumors, all of which were intramedullary spinal and all of which displayed LOH 22q. Allelic loss on 22q was found in 20 cases and was significantly more frequent in intramedullary spinal ependymomas than in tumors in other locations. LOH 11q was found in 7 patients and exhibited a highly significant inverse association with LOH 22q (p<0.001). A hemizygous MEN1 mutation was identified in 3 tumors, all of which were recurrences from the same patient. Interestingly, the initial tumor corresponded to WHO grade II and displayed LOH 11q but not yet a MEN1 mutation. In 2 subsequent recurrences, the tumor had progressed to anaplastic ependymoma (WHO grade III) and exhibited a nonsense mutation in exon 10 of MEN1 (W471X) in conjunction with LOH 11q. This suggests that loss of wild-type MEN1 may be involved in the malignant progression of a subset of ependymomas. To conclude, our findings provide evidence for different genetic pathways involved in ependymoma formation and progression, which may allow to define genetically and clinically distinct tumor entities.

Parkinson's disease and the ability to drive.

Criteria for assessment of the ability to drive in Germany are based on guidelines published by the Gemeinsamer Beirat für Verkehrsmedizin and incorporated into the legislation. Decisions relating to the ability to drive must always be taken on an individual basis. In parkinsonian patients the ability to drive is very often impaired by motor symptoms, psychiatric complications, multimorbidity, increased daytime sleepiness and especially by cognitive disturbances. Increased daytime tiredness is common in Parkinson's disease with additional sedative effects of all dopaminergic agents (e. g., pramipexole, ropinirole). Unwanted falling asleep (e. g., at the wheel) can be avoided if notice is taken of the early signs of tiredness. A recommendation is included how to advise patients with Parkinson's disease treated with a dopamine agonist regarding the ability to drive.

Workshop I: Parkinson's disease and sleep--results of the group discussion.

The group agreed on the facts that unwanted sleep onset has been observed after non-ergot as well as ergot dopamine agonists, that patients on these drugs need to be warned, that patients who have experienced sleepiness already must not drive a car unless the dosage is lowered and sleepiness has vanished, that a genetic predisposition for narcoleptic cataplexy has to be ruled out, that predictors of so-called sleep attacks need to be explored individually with the help of sleepiness scales and collectively in a careful study, respectively.

[1st long-term double-blind study of effectiveness and dyskinesia prevention of ropinirol]. / Erste doppelblinde Langzeitstudie zum Nachweis der Wirksamkeit und Dyskinesieprophylaxe von Ropinirol.

Psychiatric symptoms and motor fluctuations are frequently occurring late sequelae of long-term therapy with L-dopa. Up to 80% of patients on L-dopa therapy suffer from disturbing dyskinesias, with onset during the first few years after beginning treatment. In particular, younger and middle-aged patients with idiopathic parkinsonian syndrome may develop dyskinesias in the early years of L-dopa therapy. We propose that these particular patient groups should initially be treated with a dopamine agonist--if possible in monotherapy but at least in a dopamine agonist-dominated combination therapy with L-dopa. In this paper, we discuss the reasons for these recommendations, which are based on the findings of the first double-blinded study in which L-dopa was compared with ropinirole, a nonergot dopamine agonist, over a 5-year period. The main results of this study are as follows: At least 1/3 of patients in the ropinirole group could be treated with the dopamine agonist in monotherapy over 5 years. Treatment in the ropinirole group was as effective as in the L-dopa group. Despite equal effectiveness of both drugs, the incidence of dyskinesias was considerably lower with ropinirole (5%) than with L-dopa (36%). The long-term experience gained in this 5-year study support our recommendations to use dopamine agonists early and as the preferred drug of choice in the treatment of Parkinson's disease.

[Spontaneous vertebral arteriovenous fistula. Detection and treatment follow-up with color-coded duplex ultrasound]. / Spontane vertebrale arteriovenöse Fistel. Nachweis und Therapiekontrolle mit der farbkodierten Duplexsonographie.

Spontaneous or traumatic arteriovenous fistulae between vertebral artery and the surrounding venous plexus may cause vertebrobasilar hypoperfusion by steal effects. We report on a 71-year-old man presenting with vertigo. Duplex sonography revealed a vertebral arteriovenous fistula at the C4/5 level with the typical perivascular color Doppler artifact and hyperperfusion in the supplying arteries and draining veins. Angiography confirmed the findings; the consequently performed endovascular embolization using platin coils and silicon balloon removed the symptoms immediately. Ultrasonographic follow-up examinations within 5 months demonstrated the success of therapy showing only low-flow fistula yet. This case demonstrates that early detection of a vertebral arteriovenous fistula by duplex sonography is highly beneficial because efficient treatment modalities are available.

Cervical carotid artery vasospasms causing cerebral ischemia: detection by immediate vascular ultrasonographic investigation.

BACKGROUND: The etiology of cerebral ischemic accidents in young adults often remains unclarified. CASE DESCRIPTION: A 32-year-old woman presented after multiple episodes of left monocular visual impairment and right-sided focal signs. MRI revealed a low-flow infarction on the left; color-coded duplex sonography (CCDS), however, showed normal vascular findings. During the inpatient rehabilitation, a renewed visual impairment occurred; an immediate CCDS examination now demonstrated a filiform stenosis of the left internal carotid artery (ICA) 4 cm above the origin and indirect signs of a severe stenosis of the right ICA. Results of a follow-up examination 18 hours later were again normal. Six weeks later, on reoccurrence of visual impairment, a reversible stenosis of the left ICA was again demonstrated. A search for possible causes of vasospasm was unsuccessful. After treatment with calcium antagonists the patient was free of complaints (with the exception of 3 very short attacks of visual impairment) during the following 12 months. CONCLUSIONS: Cervical carotid artery vasospasms can apparently occur spontaneously without a mechanical trigger. Because their detection is difficult, vasospasms may go undetected.

[Lateral cranial dural fistula. Detection with Doppler and duplex ultrasound]. / Laterale kraniale Durafistel. Nachweis mit Doppler- und Duplexsonographie.

Cranial dural fistulae are rare; when they occur, it is usually difficult to detect them at an early stage. With a view to the question of possible progress in diagnosis we now report on seven patients with lateral dural fistulae fed by branches of the external carotid artery. The examination was carried out before selective arteriography using cw-Doppler sonography and colour coded duplex sonography in combination. Sonographic criteria for detection of hyperperfusion take account of flow velocity as well as pulsatility. In all cases hyperperfusion of the external carotid artery was detected. In most of these cases pathologic findings were also observed at the occipital artery, and more rarely in the contralateral external carotid artery or the ipsilateral vertebral artery, in addition. A possible source of error arising from confusion of blood vessels was present with the cw-Doppler sonography, but not for colour coded duplex sonography. Therefore, cranial dural fistulae characterized by a high shunt volume can be diagnosed correctly by indirect Doppler sonographic criteria using cw-Doppler and duplex sonography. Direct visualization of the fistula and its nidus requires additional selective arteriography, in the course of which endovascular embolization may be performed.

Blunt trauma lesions of the extracranial internal carotid artery in patients with head injury.

Blunt trauma lesions of the extracranial internal carotid artery (ICA) are rare. In our hospital 18 patients with such an injury were diagnosed. All patients were involved in traffic accidents. Most of them had sustained head injuries with fractures of the skull, mandible or maxilla. The onset of neurological signs, most frequently hemiparesis, was usually delayed. 50 percent had bilateral ICA lesions but the clinical presentation was similar to those with unilateral lesions. Mortality of patients with ICA lesions was substantial (28%).

[Parkinson therapy yesterday, today, tomorrow. Neuroprotection gains in importance]. / Parkinson-Therapie gestern, heute, morgen. Neuroprotektion gewinnt an Bedeutung.

Owing to a lack of knowledge of the pathophysiology and pathochemistry of Parkinson's disease, conservative treatment was long restricted to the treatment of symptoms. In recent decades, as the role of dopamine became better known, progressive improvements in therapy were achieved, which initially meant the administration of the precursor, L-Dopa, of the primarily non-replaceable neurotransmitter, and later augmentation of the activity of dopamine in addition. Amantadine, a highly effective drug with a wide spectrum of action and a high level of tolerability, was successfully introduced in 1969. The recently discovered NMDA antagonism, also in conjunction with a description of the mechanism of action of amantadine, which makes it possible to inhibit the effect of excitatory amino acids--in particular glutamate--in the CNS, led to the principle of neuro-protection, which is now considered the key to the treatment of Parkinson's disease.