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J Herzog

Publications and source records attributed to J Herzog.

At least 19 recordsLinked to original sources
PubMed2006

Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL. METHOD: The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 +/- 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points. RESULTS: The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint. CONCLUSIONS: This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.

Adult↗
PubMed2005

Effect of propofol anesthesia on pallidal neuronal discharges in generalized dystonia.

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.

Action Potentials↗
PubMed2005

1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1.

BACKGROUND: About 20% of patients with familial hemiplegic migraine (FHM) develop progressive cerebellar signs. Genetic studies have established an association with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar involvement are largely unknown. OBJECTIVE: To use proton MR spectroscopy (1H-MRS) to investigate metabolic alterations in the cerebellum as well as cortical regions known to be involved in the propagation of migraine aura. METHODS: Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy control subjects were studied. Eleven patients had clinical signs of cerebellar involvement. LCModel fits were used to estimate absolute concentrations of N-acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing compounds, total creatine, and lactate in the superior cerebellar vermis (SCV), parietal cortex, and occipital cortex. To control for atrophy effects, automated image segmentation was performed using SPM99. The brain parenchyma fraction (BPF) was determined for all three regions. RESULTS: Compared with controls, the brain parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was significantly elevated in the SCV of patients with FHM. In contrast, no metabolite alterations were found in supratentorial regions. BPF and NAA in the SCV significantly correlated with cerebellar scores, in particular, gait ataxia. CONCLUSIONS: The findings suggest that there is a regionally distinct neuronal impairment in the superior cerebellar vermis that exceeds macroscopic tissue loss. Correlations with clinical scores emphasize the functional relevance of localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels. These measures may be useful to monitor disease progression. The observed reduction in glutamate may in part reflect impaired glutamatergic neurotransmission.

Adolescent↗
PubMed2005

Deep brain stimulation for idiopathic or secondary movement disorders.

Deep brain stimulation has gained increasing interest in the treatment of movement disorders. Presenting our clinical series of 179 patients operated upon since 1999, the indications, risks and benefits for the patients are discussed in order to further improve the techniques and their applications.

Deep Brain Stimulation↗
PubMed2004

Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants.

A1A2 Na+/K+-ATPase mutations cause familial hemiplegic migraine type 2 (FHM2). The authors identified three putative A1A2 mutations (D718N, R763H, P979L) and three that await validation (P796R, E902K, X1021R). Ten to 20% of FHM cases may be FHM2. A1A2 mutations have a penetrance of about 87%. D718N causes frequent, long-lasting HM, and P979L may cause recurrent coma. D718N and P979L may predispose to seizures and mental retardation. A1A2 does not play a major role in sporadic HM; only one variant, R383H, occurred in 1 of 24 cases.

Adolescent↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts.

BACKGROUND: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. OBJECTIVE: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). METHODS: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. RESULTS: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (+/- 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (+/- 1.0) lateral, 1.9 mm (+/- 1.4) posterior, and 1.6 mm (+/- 2.1) ventral to the midcommissural point. CONCLUSIONS: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.

Aged↗
PubMed2002

Magnetic resonance imaging-based morphometry and landmark correlation of basal ganglia nuclei.

The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.

Adult↗
PubMed2002

MRI- and skull x-ray-based approaches to evaluate the position of deep brain stimulation electrode contacts--a technical note.

Deep brain stimulation (DBS) has developed into an established therapy for the treatment of movement disorders, most commonly Parkinson's disease and tremor of different etiology. The subthalamic nucleus (STN) has evolved as the preferred target for DBS in patients with idiopathic Parkinson's disease. The principal target for DBS in tremor patients is the ventrolateral thalamus which has been explored for ablative procedures (thalamotomy) for some decades. Detailed information about the exact site of chronic stimulation, i.e. the location of the active electrode contacts, are important to map the actual subcortical structures modulating the therapeutic effects of DBS. We compared two different methods not requiring intra-operative teleradiography to determine the stereotactic coordinates of single electrode contacts, (i) correlation of pre- and post-operative MRI, and (ii) post-operative stereotactic skull x-ray. For seven patients implanted bilateral with quadripolar DBS electrodes the coordinates for each contact were determined by both approaches. This revealed for a total of 56 electrode contacts a median euclidean 3D-difference between both methods of 1.18 mm (range 0.42 to 1.93 mm). These data suggest that both approaches may be used to determine the position of single electrode contacts.

Electric Stimulation Therapy↗
PubMed2002

Technical complication in deep brain stimulation.

With a growing number of patients treated with deep brain stimulation (DBS) operations for both hardware-related complications and routine replacements of impulse generators will be performed more frequently. Failure of DBS systems have to be analyzed thoroughly as this thwarts the enormous efforts required for proper electrode implantation and operative revisions increase the morbidity associated with DBS. A female patient implanted with DBS electrodes for advanced Parkinson's disease presented with straining of the right extension lead and deteriorating gait because of electrode migration. This was due to a malpositioned set screw connector adapting the electrode lead to the extension wire which had been placed below the mastoid process. Following surgical revision with implantation of a new electrode into the STN, electrode dislocation recurred requiring another surgical revision. This was due to renewed connector migration from its parietal position into the cervical region. Straining of extension leads should be recognized as a warning sign for (imminent) electrode dislocation or lead fracture. This may just be the case with connectors located below the mastoid process or in the cervical region, a risk which appears to be increased further with reduced-length extensions. Renewed dislocation of revised extensions may be prevented by securing the position of the connector (e.g. with manipulates).

Electric Stimulation Therapy↗
PubMed2001

NOTCH3 mutation involving three cysteine residues in a family with typical CADASIL.

Mutations in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke and vascular dementia. All CADASIL mutations identified so far result in the loss or gain of one cysteine residue within epidermal growth factor (EGF)-like repeat domains. Here an in-frame deletion causing a loss of three cysteine residues within EGF repeat 6 is reported. These data are consistent with the hypothesis that the change toward an odd number of cysteine residues within a given EGF repeat and therefore an unpaired, reactive cysteine residue is the common and critical molecular event in CADASIL.

Adult↗
PubMed2001

Effects of bilateral subthalamic nucleus stimulation on parkinsonian gait.

Gait analysis was carried out to assess the effects of L-dopa and bilateral subthalamic nucleus stimulation on gait velocity, cadence, stride length, and gait kinematics in nine patients with PD. Substantial effects of bilateral subthalamic nucleus stimulation on gait, with an increase in gait velocity and stride length comparable to that of a suprathreshold L-dopa dose, were found. Interestingly, stride length was more improved by L-dopa and cadence more by subthalamic nucleus stimulation. In two patients with freezing during the "on" period, subthalamic nucleus stimulation failed to reduce this symptom effectively.

Antiparkinson Agents↗
PubMed2001

A magnetic resonance imaging study of the cervical cord of patients with CADASIL.

The authors obtained MR and magnetization transfer (MT) imaging of the cervical cord from 25 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). They found no conventional MR abnormalities, but a reduced peak height of the MT ratio (MTR) histogram. This suggests a reduced amount of "truly" normal cord tissue in CADASIL. A significant correlation was found between the extent of brain lesions and cord MTR, suggesting wallerian degeneration as the substrate of the cord MTR changes.

Adult↗
PubMed2001

Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study.

OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.

Adult↗
PubMed2001

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.

Adult↗
PubMed2000

Fixation of transsynaptically transported WGA-HRP and fluorescent dyes used in combination.

The transsynaptic transport of WGA-HRP is a powerful tool for the identification of last order interneurones in the spinal cord, but differentiation of primarily labelled motoneurones from transsynaptically labelled interneurones can be difficult. We therefore combined the transsynaptic labelling of interneurones with WGA-HRP and the labelling of motoneurones with fluorescent dyes (fluorogold, red beads, fast blue, DAPI) by injecting a mixture of the tracers into the nervi mediani of rats. The influence of different fixatives on the simultaneous preservation of WGA-HRP and fluorescence is evaluated. It is shown that, of several perfusion protocols, only perfusion with paraformaldehyde in addition to 1.4% lysine and 0.23% periodate allowed simultaneous visualisation of transsynaptic WGA-HRP and fluorescent dyes.

Acetaldehyde↗
PubMed2000

Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.

The pathomechanism of familial hypokalemic periodic paralysis (HypoPP) is a mystery, despite knowledge of the underlying dominant point mutations in the dihydropyridine receptor (DHPR) voltage sensor. In five HypoPP families without DHPR gene defects, we identified two mutations, Arg-672-->His and -->Gly, in the voltage sensor of domain 2 of a different protein: the skeletal muscle sodium channel alpha subunit, known to be responsible for hereditary muscle diseases associated with myotonia. Excised skeletal muscle fibers from a patient heterozygous for Arg-672-->Gly displayed depolarization and weakness in low-potassium extracellular solution. Slowing and smaller size of action potentials were suggestive of excitability of the wild-type channel population only. Heterologous expression of the two sodium channel mutations revealed a 10-mV left shift of the steady-state fast inactivation curve enhancing inactivation and a sodium current density that was reduced even at potentials at which inactivation was removed. Decreased current and small action potentials suggested a low channel protein density. The alterations are decisive for the pathogenesis of episodic muscle weakness by reducing the number of excitable sodium channels particularly at sustained membrane depolarization. The results prove that SCN4A, the gene encoding the sodium channel alpha subunit of skeletal muscle is responsible for HypoPP-2 which does not differ clinically from DHPR-HypoPP. HypoPP-2 represents a disease caused by enhanced channel inactivation and current reduction showing no myotonia.

Action Potentials↗