[Spontaneous craniocervical dissection]. / Spontane Dissektionen der hirnversorgenden Arterien.

Spontaneous craniocervical dissection is one of the main causes of stroke in juvenile and middle-aged patients. It is caused by intramural hematoma which may result in stenosis or even occlusion of the artery. Clinical manifestation varies from local pain to ischemic complications. The imaging modality of choice is magnetic resonance imaging (MRI) which is able to detect all characteristic signs of dissection. Intramural hematoma is detected with thin slice fat-saturated 3D black-blood images. However, with the use of special imaging techniques, questionable findings can be clarified and especially the more difficult to detect intradural dissection can be accurately diagnosed. Acute treatment depends on the severity of neurological symptoms and their duration. Factors like the location of the dissection, cerebral infarction or hemorrhage influence the choice of medication for primary and secondary prophylaxis. Resorption of the intramural hematoma often leads to spontaneous recanalization within a few months.

[Time is brain : Time management in acute stroke treatment]. / "Time is brain" : Zeitmanagement in der akuten Schlaganfallversorgung.

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rt-PA) and interventional thrombectomy are evidence-based causative therapies in acute stroke; however, the clinical benefit for the patient has been proven to be highly time-dependent. METHODS: A review of critical time intervals in acute stroke management and possibilities for modification is presented. RESULTS: Both prehospital and in-hospital times can be reduced with proven clinical benefits. The means to achieve time reductions are diverse and require clear workflow guidelines and continuous training. CONCLUSION: Optimization of time management during the complete acute diagnostics and treatment procedure by avoiding specific delays and streamlining universal workflow is of utmost importance regarding the efficiency and safety of treatment.

Substantia nigra hyperechogenicity is related to decline in verbal memory in healthy elderly adults.

BACKGROUND AND PURPOSE: Deficits in cognition have been reported in Parkinson's disease (PD) already in the early and even in the pre-motor stages. Whilst substantia nigra hyperechogenicity measured by transcranial B-mode sonography (TCS) represents a strong PD marker and is associated with an increased risk for PD in still healthy individuals, its association with cognitive performance in prodromal PD stages is not well established. METHODS: Two different cohorts of healthy elderly individuals were assessed by TCS and two different neuropsychological test batteries covering executive functions, verbal memory, language, visuo-constructional function and attention. Cognitive performance was compared between individuals with hyperechogenicity (SN+) and without hyperechogenicity (SN-). RESULTS: In both cohorts, SN+ individuals performed significantly worse than the SN- group in tests assessing verbal memory (word list delayed recall P = 0.05, logical memory II P < 0.017). Significant differences in Mini-Mental State Examination score (cohort 1, P = 0.02) and executive function tests (cohort 2, Stroop Color-Word Reading, P = 0.004) could only be shown in one of the two cohorts. No between-group effects were found in other cognitive tests and domains. CONCLUSIONS: These results indicate that individuals with the PD risk marker SN+ perform worse in verbal memory compared to SN- independent of the assessment battery. Memory performance should be assessed in detail in individuals at risk for PD.

Peri-interventional Subarachnoid Hemorrhage During Mechanical Thrombectomy with stent retrievers in Acute Stroke: A Retrospective Case-Control Study.

BACKGROUND: Mechanical thrombectomy with stent retrievers in acute stroke has emerged as a promising new technique with the highest recanalization rate of the therapeutic procedures available so far. However, endovascular treatment is also associated with the risk of specific complications. One of those is the occurrence of peri-interventional subarachnoid hemorrhage (SAH), which has been reported in 5-16 % of the cases. Interestingly, this rate is higher than that of angiographically detectable perforations (0-3 %), leaving the majority of peri-interventional SAH to be due to angiographically occult perforations. Little is known about the influence of this finding on clinical outcome. The purpose of this study was to investigate the clinical relevance of SAH due to occult perforations during thrombectomy with stent retrievers. METHODS: Postinterventional computed tomography (CT) scans of 217 consecutive patients with acute occlusions of intracerebral arteries who were treated with stent retrievers in our department between October 2009 and October 2012 were retrospectively analyzed. RESULTS: SAH was found on postinterventional CT scans in 5.5 % of the cases. Seven cases were included for further analysis and matched to controls by the following characteristics: (1) site of occlusion, (2) result of the recanalization procedure according to the modified thrombolysis in cerebral infarction score, (3) administration of intravenous recombinant tissue plasminogen activator, (4) presence of proximal extracranial occlusion, (5) age, and (6) sex. Comparison of the angiographic data of the two cohorts showed no significant difference in the length of the procedures or the number of maneuvers needed for recanalization, nor were there significant differences in clinical outcomes as measured by NIHSS and mRS scores. Secondary symptomatic ICH occurred in one case in either cohort and led to death in both cases. The rate of asymptomatic ICH within the first 24 h after recanalization was significantly higher in the group with peri-interventional SAH (57 vs. 0 %, P = 0.018). CONCLUSIONS: This small retrospective case-control study did not reveal a significant influence of peri-interventional SAH due to angiographically occult perforations on neurologic outcome of patients treated with stent retrievers.

The PRIPS study: screening battery for subjects at risk for Parkinson's disease.

BACKGROUND AND PURPOSE: Screening batteries to narrow down a target-at-risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinson's disease (PD). METHODS: The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD-free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity (SN+). RESULTS: After 3 years follow-up 11 subjects had developed PD. In this analysis of the secondary outcome parameters, sensitivity and specificity of baseline markers for incident PD were calculated in 1352 subjects with complete datasets (10 PD patients). The best approach for prediction of incident PD comprised three steps: (i) prescreening for age, (ii) primary screening for positive family history and/or hyposmia, and (iii) secondary screening for SN+. CONCLUSION: With this approach, one out of 16 positively screened participants developed PD compared to one out of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a specificity of 90.6% and a positive predictive value of 6.1%. These values are higher than for any single screening instrument but still too low for a feasible and cost-effective screening strategy which might require longer follow-up intervals and application of additional instruments.

Relation of risk factors and putative premotor markers for Parkinson's disease.

As both risk and premotor markers are increasingly discussed to play a key role in the pre-diagnostic phase of Parkinson's disease (PD) the aim of this study was to determine the relation between the risk factors hyperechogenicity of the substantia nigra (SN+) and/or positive family history of PD (faPD+) and putative premotor markers for PD. In a cross-sectional analysis of data of the PRIPS cohort, 1,149 volunteers older than 50 years free of PD were included. In addition to the risk factors SN+ and faPD+, olfactory dysfunction was tested using the Sniffin' sticks test and motor examination was performed. History of depression and constipation was evaluated by a semi-structured interview. Of all 1,149 individuals, 880 had none of the risk markers (76.6%), 143 persons (12.4%) had SN+, 84 (7.3%) were classified as faPD+ and 42 (3.7%) persons had both risk factors. Volunteers with SN+ showed olfactory dysfunction and mild motor impairment (p ≤ 0.001) more often. Depression was more prominent in individuals having two risk factors (p = 0.05). An accumulation of premotor markers was seen in the SN+ group with or without concomitant faPD+, but not in persons with faPD+ only. The profile of premotor markers seems to differ in participants having SN+ and/or faPD+, with SN+ showing the overall highest association with most premotor markers, which implies that SN+ might be a strong indicator for a neurodegenerative process.

Stent-assisted mechanical recanalization for treatment of acute intracerebral artery occlusions.

BACKGROUND AND PURPOSE: The purpose of this study was to demonstrate a new approach to the use of a self-expanding stent in the treatment of acute ischemic stroke. METHODS: Twenty-two consecutive patients with acute intracerebral artery occlusions were treated with a self-expandable intracranial stent, which was withdrawn in its unfolded state. For this technique, we used the Solitaire AB/FR, which is the only intracranial stent that is fully recoverable. Eight patients had an occlusion of the basilar artery, 12 had a middle cerebral artery occlusion, and 2 had terminal carotid artery occlusions; 6 of these had to be treated first for an acute occlusion originating in the internal carotid artery. Recanalization results were assessed by follow-up angiography immediately after the procedure. Neurologic status was evaluated before and after treatment (90-day follow-up) according to the National Institutes of Health Stroke Scale and modified Rankin scale. RESULTS: Successful revascularization was achieved in 20 of 22 (90.9%) patients (thrombolysis in cerebral infarction [TICI] 2a/b and 3), a TICI 3 state was accomplished in 12 patients, and partial recanalization or slow distal branch filling with filling of more than two-thirds of the vessel territory was achieved in 8 patients (TICI 2b). There was immediate flow restoration in 21 of 22 (95.4%) cases after deployment of the device. The stent was removed in its unfolded state in all patients. The mean time from stroke symptom onset to recanalization was 277 minutes, with a standard deviation of 118 minutes. Mean National Institutes of Health Stroke Scale score on admission was 19.4, with a standard deviation of 5.7. Almost two-thirds of the patients (63.6%) improved by > 10 points on the National Institutes of Health Stroke Scale at discharge, and 50% showed a modified Rankin scale score of ≤ 2 at 90 days (59% with a modified Rankin scale ≤ 3). Mortality was 18.1%. In 1 case, an asymptomatic intracranial hemorrhage was detected on control computed tomography, and 2 patients had a symptomatic intracranial hemorrhage. CONCLUSIONS: Withdrawal of an unfolded, fully recoverable, intracranial stent yielded very promising angiographic and clinical results. It combines the advantages of prompt flow restoration and mechanical thrombectomy.

Substantia nigra echomorphology and motor cortex excitability.

The aim of our study was to investigate the relation between substantia nigra (SN) echomorphology and indices of motor cortex excitability. Nigral hyperechogenicity in healthy individuals is thought to represent an SN abnormality or predisposition to Parkinson's disease (PD) and its prevalence is greater in the very old. Our study involved 20 old healthy subjects (aged 72-84 years) known to have normal (n=10) or abnormal (n=10) SN echomorphology. All were in good health with no overt neurological signs. SN morphology was assessed with transcranial sonography through the pre-auricular bone window. Motor cortical excitability and intracortical inhibition were assessed with transcranial magnetic stimulation (TMS) over the first dorsal interosseus motor area. Single stimuli were delivered during relaxation and voluntary contraction and paired stimuli were delivered during relaxation. Each cortical hemisphere was analysed separately. The response to single-pulse TMS (in motor cortex ipsilateral to the target SN) did not differ between groups. However, a significant difference between groups was observed in the paired pulse paradigm (conditioning stimulus intensity: 70% resting motor threshold; interstimulus interval: 2 ms). The conditioned motor evoked potential amplitude was significantly larger ipsilateral to the hyperechogenic SN than in controls (P=0.014). Thus, healthy subjects with SN hyperechogenicity exhibit significantly less intracortical inhibition within the motor cortex than subjects with normal echomorphology. Decreased intracortical inhibition is also observed in PD patients. This study provides further evidence that SN hyperechogenicity in healthy individuals is associated with changes characteristic of PD supporting a role for this feature as a vulnerability marker or state marker for subtle nigral dopaminergic dysfunction.

Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET.

Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinson's disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN-) by a magnetic resonance imaging method (MRI; T2 relaxation times) known to reveal tissue inhomogeneity following abnormal iron content and by F-Dopa PET to assess nigrostriatal function.

Cross-sectional study discloses a positive family history for Parkinson's disease and male gender as epidemiological risk factors for substantia nigra hyperechogenicity.

Hyperechogenicity of the substantia nigra (SN) has been proposed to be a typical finding in Parkinson's disease (PD) and a marker of vulnerability to nigrostriatal dysfunction in healthy subjects. This large cross-sectional study including 1120 subjects older than 50 years without any signs of PD was performed to evaluate the association of SN hyperechogenicity and other proposed epidemiological risk factors for PD. Among all variables assessed only family history of PD and male gender proved to be significantly associated with SN hyperechogenicity, indicating a genetic predisposition for the ultrasound marker.

Substantia nigra echomorphology in the healthy very old: Correlation with motor slowing.

Transcranial sonography reveals an increase in echogenicity in the substantia nigra of patients with idiopathic Parkinson's disease. Marked hyperechogenicity has also been described in 9% of the healthy population and is associated with subtle clinical or functional neuroimaging findings suggestive of changes in nigrostriatal function. It has therefore been hypothesised that a hyperechogenic substantia nigra represents an early stage of nigral degeneration or a predisposition for Parkinson's disease. In the present study, we correlated sonographic findings with motor and cognitive deficits in a group of healthy, very elderly subjects. Marked and moderately increased substantia nigra echogenicity was present in 25% and 21% of our healthy, very elderly subjects, respectively, and correlated strongly with the presence of extrapyramidal symptoms in the absence of cognitive deficits. The high incidence of substantia nigra hyperechogenicity measured in our very elderly subjects compared with previous TCS studies suggests that the prevalence of this feature increases with age and is consistent with the higher prevalence of Parkinson's disease in advanced age, as well as the increased frequency of extrapyramidal symptoms. Our results indicate that this simple technique can be used to identify and quantify brain changes associated with subtle motor dysfunction in the very elderly.

Application of transcranial sonography in extrapyramidal disorders: updated recommendations.

Transcranial sonography (TCS) has been proven to be a valuable tool in the diagnosis and differential diagnosis of extrapyramidal disorders, supplementing clinical and pathophysiological information that may be obtained by other neuroimaging techniques. Growing interest and increased application of TCS in extrapyramidal disorders require adherence to standardised principles concerning examination procedure and parameter settings of the ultrasound machine in order to ensure comparable results. This article provides an overview of these principles and typical findings in distinct extrapyramidal disorders.

Differentiation of Parkinson's disease and atypical parkinsonian syndromes by transcranial ultrasound.

Neuroimaging is known to complement clinical findings in the diagnostic work up of parkinsonian syndromes. Recently, transcranial ultrasound was reported to have a high diagnostic yield in differentiating idiopathic Parkinson's disease (IPD) from atypical parkinsonian syndromes. This report summarises the sonographic findings of 102 patients with IPD, 34 patients with multiple system atrophy, and 21 patients with progressive supranuclear palsy. Increased echogenicity of the substantia nigra is predictive for IPD whereas a low echogenic substantia nigra, particularly when combined with a hyperechogenic lentiform nucleus, strongly suggests an atypical Parkinsonian syndrome. The underlying causes for the differential echo pattern of the substantia nigra remain unknown.

The role of alpha-synuclein gene multiplications in early-onset Parkinson's disease and dementia with Lewy bodies.

BACKGROUND: A triplication of the alpha-synuclein gene was found to cause autosomal dominant Lewy body disease in two distinct families. METHOD: We searched for alterations of alpha-synuclein gene dosage and analysed the entire coding region for point mutations in 54 dementia with Lewy body disease (DLB) and in 103 young onset Parkinson's disease (PD) patients from Central Europe. RESULTS: We could not detect any quantitative alterations in the gene dosage of alpha-synuclein. Mutational screening of the entire coding region of alpha-synuclein revealed only one silent mutation V3V (adenine9guanine) in one case. CONCLUSIONS: Thus, this phenomenon appears not to be a major cause in the pathogenesis of sporadic DLB and young onset PD in this European population.

Echogenic substantia nigra in patients with orthostatic tremor.

OBJECTIVES: Previous studies suggest that the nigrostriatal dopaminergic transmission is impaired in patients with primary orthostatic tremor. METHODS: We used transcranial sonography (TCS) to examine the morphology of the substantia nigra (SN) in four patients with primary orthostatic tremor (OT). RESULTS: TCS revealed an SN echogenicity in all patients, in three patients unilaterally, in one patient bilaterally. CONCLUSIONS: Our data suggest nigrostriatal dopaminergic deficits in OT patients. The exact impact of these dopaminergic deficits on OT generation is unclear.

Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease.

BACKGROUND: Transcranial ultrasound may be used to detect increased iron levels of the substantia nigra (SN) in patients with Parkinson disease (PD) and in control subjects. It is not known whether iron accumulation in PD is a primary or secondary phenomenon. However, sequence variations in genes involved in iron metabolism have been linked to basal ganglia disorders. One of these is ceruloplasmin (Cp), which is vitally involved in iron transport across the cell membrane. METHODS: One hundred seventy-six patients with PD according to the UK Brain Bank criteria and 180 ethnically matched control subjects, who were previously examined for SN iron signal changes by transcranial ultrasound, were examined for mutations in the Cp gene using denaturing high-performance liquid chromatography and subsequent sequencing for verification of unequivocal signals. Immunohistochemistry of PD midbrains was performed to examine the presence of Cp in Lewy bodies. RESULTS: Five novel missense variations were detected. One of these (I63T) was found in a single PD patient. A known variation (D554E) was significantly associated with PD and the ultrasound marker for increased SN iron levels. Moreover, a third sequence variation (R793H) was found to segregate with the ultrasound marker for increased iron levels in patients and control subjects. Immunohistochemistry demonstrated that Cp co-localizes with Lewy bodies in PD. CONCLUSIONS: Detection of sequence variations in a single Parkinson disease (PD) patient or associated with the ultrasound marker for increased substantia nigra iron levels and the presence of ceruloplasmin (Cp) immunoreactivity in Lewy bodies underline a suspected role for Cp in the pathogenesis of PD. Further functional analyses are warranted to investigate whether these variations are causally linked to the complex pathogenesis of PD in a subset of cases.

Screening for mutations of the IRP2 gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra.

IRP2 plays an important role in brain iron metabolism. We recently identified an increased amount of iron in patients with Parkinson's disease (PD) and hyperchogenicity of the substantia nigra (SN). Therefore, the IRP2 gene was screened for mutations in 176 PD patients with increased echogenicity of the SN. We identified one non-synonymous polymorphism (I888V) in exon 21 and a -88C > T polymorphism in the promoter region of IRP2 at similar frequencies in patients and controls without increased SN iron levels. In one patient a -74C > T variation was found which was not present in the control group. Our data indicate that mutations in the IRP2 gene are not a common cause of PD associated with SN iron accumulation.

Does ultrasound disclose a vulnerability factor for Parkinson's disease?

Transcranial ultrasound is a new tool allowing the detection of abnormalities in the echomorphology of the substantia nigra (SN) in patients with Parkinson's disease (PD). Several lines of evidence suggest that the changes in the echo-pattern represent a risk factor as: i) the majority of PD patients exhibit this echo-feature, ii) the presence of such changes in healthy controls is related to a reduced (18)F-Dopa-uptake and clinical signs of nigrostriatal dysfunction. The reason for the change of echogenicity is suggested to be an increased iron content in the substantia nigra causing oxidative stress and neuronal cell damage. This hypothesis of changes in SN echomorphology reflecting a risk factor of PD has to be proved in longitudinal studies.

Treatment of closed tibia shaft fractures: a survey from the 1997 Orthopaedic Trauma Association and Osteosynthesis International--Gerhard Küntscher Kreis meeting.

OBJECTIVE: To identify any consensus of opinion regarding treatment and outcome of a closed mid-shaft tibia fracture among orthopedic surgeons. DESIGN: Survey. SETTING: 1997 combined meeting of the Orthopaedic Trauma Association and Osteosynthesis International-Gerhard Küntscher Kreis. MAIN OUTCOME MEASUREMENT: Percentage of responses to key questions. Proportion test (nonparametric) for statistical significance. RESULTS: There is no consensus of opinion regarding treatment for this fracture type. Wide variation exists between and within the different subgroups of orthopaedic surgeons surveyed. CONCLUSIONS: This brings into focus the spectrum of acceptable care for the management of fractures. More studies must be conducted to identify optimal treatment for closed mid-shaft tibia fractures.