Ludwig Niehaus

Contemporary ultrasound systems allow high-resolution transcranial imaging of small echogenic deep intracranial structures similarly as MRI: a phantom study.

Transcranial sonography (TCS) of small deep brain structures, such as substantia nigra and brainstem raphe, is increasingly used for assessment of neurodegenerative disorders. Still, there are reservations against TCS because of the smallness of evaluated structures and constraints on image resolution that is discussed to be lower compared to magnetic resonance imaging (MRI). To evaluate two different-generation TCS systems in visualizing fine intracranial structures, we studied image resolution on a phantom consisting of 0.80 mm x 1.05 mm regular meshwork of nylon threads embedded in a wet, gel-filled ex vivo human skull. Imaging was performed with a former-generation and a present-day clinical ultrasound system and for comparison with MRI. In axial direction of insonation both TCS systems resolved 0.80-mm and 1.05-mm thread-to-thread distance at depths between 55 and 120 mm using transmission frequencies > or =2.5 MHz. The meshwork, however, was recognizable as such only with the contemporary TCS system at depths between 60 and 85 mm due to its higher lateral resolution. MRI resolved the meshwork if image resolution was chosen sufficiently high but not if realistic clinical conditions were applied with its trade-offs between image SNR, resolution, total scan time, and unavoidable head motion during the latter. Hence, if the requirements for optimal TCS image resolution are fulfilled, i.e. sufficient acoustic bone window, increased echogenicity of target structure and its localization in a distance of maximum +/-15 mm from midsagittal plane, findings suggest that contemporary TCS systems achieve higher image resolution of intracranial structures in comparison not only to former-generation systems, but also to MRI under clinical conditions.

Diffusion tensor imaging of the corpus callosum differentiates corticobasal syndrome from Parkinson's disease

Differential diagnosis between patients with Corticobasal syndrome (CBS) and Parkinsons disease (PD) may be confusing, particularly in early disease stages. However, in contrast to PD, CBS shows a widespread cortical atrophy that suggests an involvement of the corpus callosum (CC). To test this hypothesis, we used diffusion tensor imaging (DTI) with a 1.5T scanner to compare 14 CBS patients, 14 PD patients, and an age-matched control group. The mean diffusivity (MD) and fractional anisotropy (FA) were determined in the whole CC and in five subdivisions. Group comparisons were performed using the Mann-Whitney U-test. We found a significantly increased MD and decreased FA in CBS patients compared to PD, particularly in the posterior truncus. No differences were found between PD patients and controls. A receiver-operating characteristics (ROC) analysis shows that the MD is particularly useful for discriminating between the two neurodegenerative diseases. Our data suggest that abnormal CC diffusivity in CBS reflects an atrophy and degraded transcallosal connectivity, making the CC a potential target to differentiate CBS from PD patients.

Involvement of motor pathways in corticobasal syndrome detected by diffusion tensor tractography.

Corticobasal syndrome (CBS) is a progressive parkinsonian disease characterized by cortical and subcortical neuronal loss. Although motor disabilities are a core feature of CBS, the involvement of motor pathways in this condition has not been completely clarified. We used magnetic resonance diffusion tensor imaging (DTI) to study corticospinal and transcallosal motor projections in CBS, and applied fiber tractography to analyze the axonal integrity of white matter projections. Ten patients with CBS were compared with 10 age‐matched healthy controls. Fiber tracts were computed using a Monte‐Carlo simulation approach. Tract‐specific mean values of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were determined. CBS patients showed a reduction of corticospinal tract (CST) fibers on the first affected side with significantly increased ADC and reduced FA values. In the corpus callosum (CC), particularly in the posterior trunk, patients also had significantly reduced fiber projections, with a higher ADC and lower FA than controls. This pattern indicates changes of the white matter integrity in both CST and CC. Thus, magnetic resonance DTI can be used to assess motor pathway involvement in CBS patients.

Levodopa-responsive posttraumatic parkinsonism is not associated with changes of echogenicity of the substantia nigra

Incapacitating posttraumatic tremor and Parkinsonian syndromes are often secondary to severe closed-head injury.1 Sonographic evaluation of the midbrain parenchyma has been postulated to be an inexpensive, noninvasive, and time-saving method in the differentiation between idiopathic Parkinson’s disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP).2 PD has been shown to be associated with hyperechogenicity of the substantia nigra (SN), which contrasts with findings in patients suffering from MSA and PSP.2 It has been suggested that this hyperechogenicity represents a pathological pattern found predominantly in PD.3,4 The value of brain parenchyma sonography for differentiation of other atypical parkinsonian syndromes remains to be determined. At present, the most reliable method for demonstration of a striatal dopaminergic deficit seems to be I-FP-CITSPECT. However, this method is expensive and not readily available. We report on a patient suffering from levodopa (L-dopa)responsive posttraumatic hemiparkinsonism with a lesion including the right midbrain and a severe ipsilateral striatal dopamine depletion as assessed by I-FP-CIT-SPECT. Brain parenchyma sonography did not demonstrate any hyperechogenicity within the SN, which contrasts findings in PD. Sonography may be an inexpensive and readily available method to differentiate between posttraumatic and idiopathic parkinsonism. A 59-year-old, previously healthy woman sustained in a pedestrian accident in 2001 a severe head injury with a predominantly left brachiofacial hemiparesis, leading to wheelchair dependency. Several weeks after the trauma, clinical signs of a left body side hemiparkinsonism developed, which comprised a slowly progressing resting tremor of the left hemibody. Additionally, speech became hypophonic, slurred, and occasionally explosive, and hypomimia developed. Furthermore, she displayed an impairment of upward gaze. Muscle tone of the partially paretic left hemibody was increased with elevated deep tendon reflexes and Babinski’s sign. There was a low-frequency, large-amplitude resting and action tremor with emphasis of the left upper extremity. Sensory function was completely normal. Cranial magnetic resonance imaging using T2-weighted fluid-attenuated inversion recovery sequences (FLAIR) revealed a right-sided rostrocaudal-orientated hypointense lesion including the pyramidal tract and the red nucleus, suggestive of hemosiderin deposit in the anterior midbrain region as a consequence of a previous hemorrhage (Fig. 1). The subthalamic nucleus was not affected. I-FP-CIT-SPECT, carried out to quantify the presumed presynaptic dopaminergic deficit, displayed a pronounced reduction of dopamine reuptake within the right striatum (right striatum/occipital reference region ratio: 1.24; left striatum/occipital reference region: 3,0; norm 2,5). Transcranial brain parenchyma sonography was carried out with a phased-array ultrasound system (Sonoline Elegra, Siemens, Germany) equipped with a 2.5-MHz transducer as described elsewhere.5 Interestingly, in contrast to the findings in patients with PD,3 brain parenchyma sonography revealed normal echogenicity of the SN (Fig. 2). Polygraphic tremor analysis of the left upper limb displayed an alternating action more than resting tremor with frequency peak of 3.2 Hz in the power spectrum, resembling Holmes’ tremor.6 Administration of 400 mg L-dopa per day led to a stable and sustained improvement of hypophonia, hypomimia, and tremor of 71% (Unified Parkinson’s Disease Rating Scale). It is well known that midbrain lesions, as in the present case, are associated frequently with movement disorders, particularly posttraumatic tremors.1 A posttraumatic tremor, which often Published online 18 November 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20323 FIG. 1. Axial MR imaging (FLAIR) of the midbrain of the patient with posttraumatic parkinsonism. A hypointense lesion (white arrow) is shown in the anterior part of the red nucleus and posterior part of the substantia nigra indicating a hemosiderin deposit due to the previous hemorrhage. Movement Disorders Vol. 20, No. 2, 2005, pp. 258–262

Increased Echogenicity of the Substantia Nigra in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

BACKGROUND Recent neurobiological models on attention-deficit/hyperactivity disorder (ADHD) as well as findings from imaging studies suggest a crucial involvement of dopaminergic midbrain nuclei, especially the substantia nigra (SN), in the pathogenesis of ADHD symptoms. The current study aimed to investigate whether alterations in the sonographic features of the SN could serve as a biological marker in ADHD patients. METHODS The current study employed transcranial sonography in 29 children and adolescents with ADHD and 27 healthy control participants to assess midbrain abnormalities in ADHD. RESULTS The ADHD patients showed an increase in echogenic size of the SN that was correlated with symptoms of inattention, hyperactivity, and impulsivity but not oppositional or dissocial symptoms. Hyperechogenicity, defined as echogenic size above the 90th percentile in the control group, was present in 48% of ADHD patients. CONCLUSIONS Our findings indicate an increased vulnerability of the nigrostriatal system in ADHD. Transcranial sonography could be successfully used in the future to explore whether ADHD patients with distinct SN hyperechogenicity constitute a specific subgroup or whether hyperechogenicity relates functionally to differences in reward processing, learning, and motor function.

Diagnosis of Parkinson’s Disease—Transcranial Sonography in Relation to MRI

Displaying the echo pattern (echogenicity) of brain tissue transcranial sonography (TCS) may provide new and complementary information to other neuroimaging methods. In contrast to conventional magnetic resonance imaging (MRI), TCS is able to detect highly characteristic changes in signal brightness of the substantia nigra (SN) in patients with idiopathic Parkinsons disease. In this review, TCS findings are related to conventional and advanced high-field brain MRI findings. On the basis of the MRI findings, especially with T2-relaxometry, the possible role of trace metals in the genesis of altered echogenicity on TCS of brain parenchyma, especially of the SN, are discussed.

147. Diffusion tensor imaging of the corpus callosum distinguishes Parkinson‘s disease from corticobasal syndrome

years; mean duration of symptoms: 2.3 ± 1.5 years) with a spastic hemiparesis due to a stroke participated after having given informed consent. In experiment 1, vibration of forearm extensors was performed with 60 Hz for 5 min. Before and after the vibration motor functions were tested by using the Box and Blocks test (B & B test), which requires the ability to grasp and move dice. First, subjects were trained until they had reached a stable baseline. Then the B & B test was repeated after an interval of 5 min to ensure stability of performance. Immediately after the vibration period, performance was re-tested, and a final test was performed after another 5 min of rest. Baseline results were determined as 100%. In experiment 2 (n = 5 subjects), TMS was used to elicit a CSP before and during forearm extensor vibration. Stimulus intensity was adjusted to 120% of the individual motor threshold. Five trials were averaged and rectified. Recordings were obtained from forearm flexors during voluntary hand and finger flexion. Both arms were studied consecutively. Results: Experiment 1. Compared to baseline, vibration significantly improved performance of the B & B test (p = 0.03; improvement of 15.3 ± 13.2%). This effect was still present after 5 min of rest (improvement of 14.7 ± 6%; p = 0.007). Experiment 2. Prior to vibration, the CSP tended to be shorter on the spastic side (97.2 ± 21.2 ms versus 106.1 ± 25.1 ms). During vibration, a prolongation of the CSP was found. This effect was present in the spastic as well as the unaffected side (paretic side: 112.5 ± 28.1 ms; p = 0.01; unaffected side: 122.5 ± 39.1 ms; p = 0.05). Subjectively, patients reported that finger extension had become easier after vibration. Conclusions: Vibration improved motor function in a spastic arm. This effect outlasted the stimulation period by at least 10 min. The lengthening of the CSP suggests that motor cortical inhibitory neurons responsible for flexor muscles were activated by extensor muscle vibration. The results support a role for vibration in the rehabilitation of spastic hemiparesis.

110. Hypoechogenicity of the substantia nigra in restless-legs-syndrome: Does it depend on imaging quality?

Background: In the recent years, studies applying transcranial sonography (TCS) of the brain parenchyma associated a hypoechogenicity of the substantia nigra (SN) with the occurrence of restless legs syndrome (RLS). A decreased echogenicity of the SN in 20 patients in comparison to that of a healthy control group was first described in 2005 (Schmidauer et al.). A larger study including 49 patients with RLS confirmed the results of an in average hypoechogenic SN in relation to ageand gendermatched control subjects. In order to replicate the data by Schmidauer and colleagues, we measured SN echogenicity in groups of patients with RLS, idiopathic Parkinson disease and healthy controls. Study: Images obtained with transcranial B-mode sonography of 28 patients suffering from RLS (RLS; 17 w, age 39–78 y, median 63 y) were compared with groups of each 28 subjects with idiopathic Parkinson syndrome (IPS; 6 w, age 42–78 y, median 64 y) and healthy controls (CON; 14 w, age 25–75 y, median 58 y). The depicted echogenic area of the SN was rated by two experienced examiners for SN AREA (mm); additional ratings were performed for the general impression of the quality of the bone window (CONTRAST, ratings: nearly no or no contrast – moderate c. – good c. [0–.5–1.0)) and a measure for the luminance of the SN (ECHO, rating equivalent to CONTRAST). The statistical analysis included AGE (three groups of similar size; <58 y, 58–65 y, >65 y) and GENDER as independent factors. Results: SN size (mean ± standard deviation) differed between groups, showing higher values for the Parkinson group (RLS: 10.5 ± 1.2 mm; IPS: 21.0 ± 1.3 mm; CON: 10,1 ± 0.95 mm). Analysis using univariate ANOVA (SPSS 11.5) with SN size as dependent variable revealed a significant main effect for the factor GROUP, validating the differences between Parkinson patients and other groups (p < .001). No significant difference was found when comparing the groups RLS and CON directly. A main effect on SN size was also found for the factors CONTRAST and ECHO (each p < .001). Also, CONTRAST correlated with ECHO (p < .001, r:0.490). No systematic correlations were found for AGE and GENDER. Discussion: In accordance with the previous studies patients with Parkinson’s disease demonstrated a larger SN AREA as patients with RLS or healthy controls. In contrast to the data provided by Godau and collaborators our data did not provide evidence for an SN hypoechogenicity in patients with RLS. Furthermore, the data demonstrated a dependency of the measured SN AREA of the factors contributing to imaging quality and SN luminance. A sufficient measure for individual imaging quality seems essential for the comparability of the findings in brain parenychyma sonography.

Is substantia nigra echogenicity related to the dopaminergic nigrostriatal impairment in Parkinson’s disease?

tant function of Kir4.1 is regulating the extracellular K+ concentration in neuronal active compartments (Neusch et al., 2005). Methods: Developmental Kir4.1 expression was assessed by immunohistochemistry in paraffin-embedded cerebellar sections at different perinatal and adult time points. Cell-specific and spatial Kir4.1 expression was determined using transgenic mice with fluorescently labeled astrocytes [TgN(GFAP-EGFP)]. Furthermore, a mouse line with genetic ablation of the Kir4.1 channel subunit was used to understand its role in cerebellar development and function. Caspase-3 labeling and Tunel indicated apoptosis. Results: Kir4.1 expression was developmentally upregulated in pre-and deep cerebellar nuclei and in the cortex of the cerebellum. At P5, Kir4.1 was found predominantly on non-neuronal cells in the inferior olive and in deep cerebellar nuclei. At P11 and in adult animals also EGFP-GFAP-positive Bergmann glia expressed Kir4.1 that overlapped with expression of a glia-specific glutamate transporter (GLAST), hereby closely ensheathing Purkinje cells (PC). On a histopathological level, cerebellar nuclei showed apoptotic neuronal cell death as early as at P5. Isolated loss of PC in the cerebellar cortex was first detected in the second postnatal week though PCs lack any detectable Kir4.1 expression. Discussion: The temporal and spatial expression pattern of Kir4.1 in pre-and deep cerebellar nuclei supports a role of glial cells in shaping active neuronal circuits in the cerebellum. PC death in the developing cortex due to Kir4.1 gene ablation may be a consequence of (i) disrupting cerebellar loops from PC to deep cerebellar nuclei and (ii) impaired perineural K+ buffering properties of Kir4.1-negative Bergmann glia that induce PC death by chronic K+ excitotoxicity in later stages of development. This study shows that loss of glial-specific ion channels can induce neuronal cell death in the cerebellum and may thus have a role in degenerative cerebellar diseases.