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Biomedical subjects

Peter Stoeter

Publications and source records attributed to Peter Stoeter.

36 records · Page 2Linked to original sources

Somatotopic organization of the corticospinal tract in the human brainstem: a MRI-based mapping analysis.

To investigate the incompletely understood somatotopical organization of the corticospinal tract in the human brainstem, we performed a voxel-based statistical analysis of standardized magnetic resonance scans of 41 prospectively recruited patients with pyramidal tract dysfunction caused by acute brainstem infarction. Motor hemiparesis was rated clinically and by the investigation of motor evoked potentials to arms and legs. Infarction affected the pons in 85% of cases. We found the greatest level of significance of affected brainstem areas between the pontomesencephalic junction and the mid pons. Lesion location was significantly more dorsal in patients with hemiparesis affecting more proximal muscles and was significantly more ventral in patients with predominantly distal limb paresis. Comparison of magnetic resonance lesion from patients with paresis predominantly affecting arm or leg did not show significant topographical differences. We conclude that a topographical arm/leg distribution of corticospinal fibers is abruptly broken down as the descending corticospinal tract traverses the pons. Corticospinal fibers, however, follow a somatotopical order in the pons with fibers controlling proximal muscles being located close to the reticular formation in the dorsal pontine base, and thus more dorsal than the fibers controlling further distal muscle groups.

Adult↗

New partially parallel acquisition technique in cerebral imaging: preliminary findings.

In MRI applications where short acquisition time is necessary, the increase of acquisition speed is often at the expense of image resolution and SNR. In such cases, the newly developed parallel acquisition techniques could provide images without mentioned limitations and in reasonably shortened measurement time. A newly designed eight-channel head coil array (i-PAT coil) allowing for parallel acquisition of independently reconstructed images (GRAPPA mode) has been tested for its applicability in neuroradiology. Image homogeneity was tested in standard phantom and healthy volunteers. BOLD signal changes were studied in a group of six volunteers using finger tapping stimulation. Phantom studies revealed an important drop of signal even after the use of a normalization filter in the center of the image and an important increase of artifact power with reduction of measurement time strongly depending on the combination of acceleration parameters. The additional application of a parallel acquisition technique such as GRAPPA decreases measurement time in the range of about 30%, but further reduction is often possible only at the expense of SNR. This technique performs best in conditions in which imaging speed is important, such as CE MRA, but time resolution still does not allow the acquisition of angiograms separating the arterial and venous phase. Significantly larger areas of BOLD activation were found using the i-PAT coil compared to the standard head coil. Being an eight-channel surface coil array, peripheral cortical structures profit from high SNR as high-resolution imaging of small cortical dysplasias and functional activation of cortical areas imaged by BOLD contrast. In BOLD contrast imaging, susceptibility artifacts are reduced, but only if an appropriate combination of acceleration parameters is used.

Artifacts↗

Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study.

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer's disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.

Aged↗

Bilateral Wallerian degeneration of the medial cerebellar peduncles after ponto-mesencephalic infarction.

Three patients with acute large paramedian ponto-mesencephalic infarctions developed a bilateral retrograde degeneration of the medial cerebellar peduncles within 4 months after the insult. In an initial magnetic resonance imaging (MRI) within the first 2 weeks, the medial cerebellar peduncles showed normal intensities, but a control MRI after 4 months showed bright hyperintensities in the T2-TSE weighted images, and moderately increased signal intensities in echo planar imaging-diffusion weighted imaging were seen, possibly representing bilateral Wallerian degeneration of the cerebellar-pontine fibers.

Aged↗

High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia.

The 'atypicality' of the antipsychotic drug, amisulpride, has been attributed to preferential extrastriatal binding. Previous investigations of striatal D2 receptor occupancy by amisulpride revealed conflicting results. The aim of this PET study was to measure the striatal occupancy by amisulpride and to correlate it with the corresponding drug plasma concentrations. Nine amisulpride-treated patients and 12 healthy volunteers serving as controls were studied with PET and [18F]desmethoxyfallypride. Occupancy values and plasma concentrations were nonlinearly fitted to an E max model. Results showed 43-85% (putamen) and 67-90% (caudate) D2-like receptor occupancy. Plasma amisulpride concentrations at the time of tracer injection, but not administered doses, were significantly nonlinearly correlated to occupancy levels (putamen: rS=0.88, p=0.0017; caudate: r S=0.78, p=0.0127). Calculated Emax was similar in both caudate and putamen, but occupancy levels were lower in caudate at lower amisulpride plasma concentrations. Calculated plasma levels to attain 60-80% receptor occupancy ranged from 119 to 474 ng/ml (caudate) and from 241 to 732 ng/ml (putamen). This reveals a broad range of plasma concentrations producing less than 80% striatal receptor occupancy. However, our data show high striatal D2-like receptor occupancies under rising plasma concentrations. Using the full range of recommended amisulpride dosage, striatal occupancies up to 90% can be measured.

Adult↗

Altered effective connectivity in drug free schizophrenic patients.

The present fMRI study aimed to investigate effective connectivity within a cortical-subcortical-cerebellar information processing network in drug free schizophrenic patients while performing a 2-back working memory task. The finding of enhanced thalamo-cortical and cortico-cortical intrahemispheric connectivity could be interpreted as a compensatory increase of neuronal connection strength consistent with a model of cortical inefficiency in schizophrenic patients. Additionally, the result could be integrated into a model of deficient thalamo-cortical filter functions. Conversely, lower interhemispheric connectivity of the frontal and parietal association cortex appears to be the functional correlate of reduced cognitive performance in schizophrenic patients. The study demonstrated the feasibility to model information processing within cognitive networks and provided additional evidence for the concept of cognitive dysmetria in schizophrenia.

Adult↗

Cerebellar speech representation: lesion topography in dysarthria as derived from cerebellar ischemia and functional magnetic resonance imaging.

BACKGROUND: Lesion topography and the pathophysiological background of dysarthria due to focal cerebellar lesions have not yet been fully clarified. OBJECTIVES: To investigate the lesion topography of dysarthria due to cerebellar ischemia and evaluate brainstem functions. DESIGN: Case studies. PATIENTS: Eighteen right-handed patients with sudden-onset dysarthria and cerebellar ischemia with and without brainstem involvement and 19 healthy, right-handed, monolingual, German-speaking volunteers. METHODS: In patients, we used multimodal electrophysiologic techniques to investigate brainstem functions. Functional magnetic resonance imaging (MRI) was performed in the 19 healthy volunteers. Activation tasks consisted of repetitive vertical silent movements of the tongue and lips at a self-paced rhythm. RESULTS: Cerebellar lesions and additional signs of brainstem involvement were observed in 11 patients with posterior inferior cerebellar artery, anterior inferior cerebellar artery, and superior cerebellar artery infarctions, respectively. In all other patients with isolated cerebellar infarction (n = 7), only the superior cerebellar artery territory (6 right-sided, 1 left-sided) was affected, and the common lesion site was the rostral paravermal region of the anterior lobe. Functional MRI in healthy volunteers indicated that the cerebellar representation of the tongue and orofacial muscles corresponds to that of the area involved in patients with cerebellar dysarthria. CONCLUSIONS: The results of this study demonstrate that articulatory movements of the tongue and orofacial muscles are involved in the activation of the rostral paravermal area of the anterior lobe. This location corresponds to the area involved in cerebellar ischemia in patients with dysarthria. Lesions in the upper paravermal area of the right cerebellar hemisphere, the site of coordination of articulatory movements of the tongue and orofacial muscles, may lead to the development of dysarthria that is unrelated to (often concomitant) brainstem infarctions.

Adult↗

Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling.

The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.

Adult↗

Asymmetry in the human primary somatosensory cortex and handedness.

Brain asymmetry is a phenomenon well known for handedness and language specialization and has also been studied in motor cortex. Less is known about hemispheric asymmetries in the somatosensory cortex. In the present study, we systematically investigated the representation of somatosensory function analyzing early subcortical and cortical somatosensory-evoked potentials (SEP) after electrical stimulation of the right and left median nerve. In 16 subjects, we compared thresholds, the peripheral neurogram at Erb point, and, using MRI-based EEG source analysis, the P14 brainstem component as well as N20 and P22, the earliest cortical responses from the primary sensorimotor cortex. Handedness was documented using the Edinburgh Inventory and a dichotic listening test was performed as a measure for language dominance. Whereas thresholds, Erb potential, and P14 were symmetrical, amplitudes of the cortical N20 showed significant hemispheric asymmetry. In the left hemisphere, the N20 amplitude was higher, its generator was located further medial, and it had a stronger dipole moment. There was no difference in dipole orientation. As a possible morphological correlate, the size of the left postcentral gyrus exceeded that of the right. The cortical P22 component showed a lower amplitude and a trend toward weaker dipole strength in the left hemisphere. Across subjects, there were no significant correlations between laterality indices of N20, the size of the postcentral gyrus, handedness, or ear advantage. These data show that asymmetry of median nerve SEP occurs at the cortical level, only. However, both functional and morphological cortical asymmetry of somatosensory representation appears to vary independently of motor and language functions.

Adult↗

Left-hemisphere dominance in early nociceptive processing in the human parasylvian cortex.

Pain perception comprises sensory and emotional dimensions. While the emotional experience is thought to be represented in the right hemisphere, we here report a left-hemisphere dominance for the early sensory component of pain perception using brain electrical source analysis of laser-evoked potentials. Ten right-handed subjects underwent several series of laser radiant heat stimuli to pairs of parallel lines on the dorsum of the left or right hand. Stimulus location and intensity were randomised independently. The sensory-discriminative aspects of pain were emphasised by asking the subjects to perform either a spatial or an intensity discrimination task and were contrasted with active distraction by mental arithmetics. Pain ratings obtained after each of the laser stimulus series revealed an analgesic effect of distraction (27%, P < 0.001). Four equivalent dipole sources were active in the latency range of 100-200 ms (bilateral operculoinsular cortex, midcingulate gyrus, postcentral gyrus). The sources in the operculoinsular cortex exhibited (a) the shortest peak latency (155 +/- 6 ms), (b) the most pronounced enhancement during spatial and intensity discrimination tasks compared to active distraction (43%, P < 0.001), and (c) a significantly stronger source activity in the left hemisphere independent of stimulation side (23%, P < 0.05). The distribution of these sources extended into the dorsal insula. The postcentral source had the longest peak latency (180 +/- 7 ms); its source strength was task-dependent (25%, P = 0.051) but exhibited no hemisphere dominance. The midcingulate source had an intermediate peak latency (169 +/- 7 ms). Its source strength was modulated by tasks, but this modulation was significant only in the latency range >200 ms (46%, P < 0.001). These findings suggest a dominant role of the left frontal operculum and adjacent dorsal insula in the early sensory-discriminative dimensions of pain processing. This region has been proposed to be the cortical projection target of nociceptive pathways from the spinal cord to the ventroposteroinferior and ventromedial (its posterior part: VMpo) thalamic nuclei.

Adult↗

EEG-related functional MRI in benign childhood epilepsy with centrotemporal spikes.

The localization of epileptic foci is an important issue in children with extratemporal epilepsies. However, the value of noninvasive methods such as the EEG-assisted functional magnetic resonance imaging (fMRI) has not been sufficiently investigated in children. As a model of extratemporal epilepsies, we studied 7 patients aged 5 to 12 (median 10) years with benign childhood epilepsy and centrotemporal (rolandic) spikes. Interictal spikes were recorded during the fMRI acquisition on a MR-compatible battery-powered digital EEG system with 16 channels. The fMRI sequences were correlated off-line with the EEG spikes and analyzed with the software Statistical Parametrical Mapping SPM99. The fMRI results demonstrated the spike-related activation in the perisylvian central region in three patients; we could not demonstrate fMRI activation despite active spiking in 2 patients, and 2 patients did not produce sufficient spikes for fMRI analysis. We currently consider the spike-related fMRI as a research tool that localizes epileptic activity in selected patients. Further improvements of the technique are necessary to allow a clinical application of this method.

Brain Mapping↗

Subchronic haloperidol downregulates dopamine synthesis capacity in the brain of schizophrenic patients in vivo.

The antipsychotic effect of neuroleptics cannot be attributed entirely to acute blockade of postsynaptic D(2)-like dopamine (DA) receptors, but may arise in conjunction with the delayed depolarization block of the presynaptic neurons and reduced DA synthesis capacity. Whereas the phenomenon of depolarization block is well established in animals, it is unknown if a similar phenomenon occurs in humans treated with neuroleptics. We hypothesized that haloperidol treatment should result in decreased DA synthesis capacity. We used 6-[(18)F]fluoro-L-dopa (FDOPA) and positron emission tomography (PET) in conjunction with compartmental modeling to measure the relative activity of DOPA decarboxylase (DDC) (k(D)(3), min(-1)) in the brain of nine unmedicated patients with schizophrenia, first in the untreated condition and again after treatment with haloperidol. Patients were administered psychometric rating scales at baseline and after treatment. Consistent with our hypothesis, there was a 25% decrease in the magnitude of k(D)(3) in both caudate and putamen following 5 weeks of haloperidol therapy. In addition, the magnitudes of k(D)(3) in cerebral cortex and thalamus were also decreased. Psychopathology as measured with standard rating scales improved significantly in all patients. The decrease of k(D)(3) in the thalamus was highly significantly correlated with the improvement of negative symptoms. Subchronic treatment with haloperidol decreased the activity of DDC in the brain of patients with schizophrenia. This observation is consistent with the hypothesis that the antipsychotic effect of chronic neuroleptic treatment is associated with a decrease in DA synthesis, reflecting a depolarization block of presynaptic DA neurons. We link an alteration in cerebral catecholamine metabolism in human brain with the therapeutic action of neuroleptic medication.

Adult↗

Diffusion-weighted MRI of cholesteatomas of the petrous bone.

PURPOSE: To investigate if primary cholesteatomas of the petrous bone show high signal in diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In this blinded study, we compared 15 patients with clinically certain cases and later surgically proven cholesteatomas vs. 12 patients with clinically acute otitis of the middle ear and 20 volunteers without petrous bone disease. Two blinded readers without knowledge of the clinical data decided in consensus agreement whether there was a pathologic signal increase in the petrous bone in an anisotropic single-shot echo-planar imaging (EPI) DWI sequence, an artifact, or no signal increase. RESULTS: Thirteen of 15 patients with cholesteatomas showed bright signal in EPI DWI, whereas 10 of 12 patients with acute otitis media and all volunteers presented the usual low signal of petrous bone. CONCLUSION: EPI DWI is a fast diagnostic method that may be an additional valuable tool in the workup of suspected cholesteatomas. The ability of this technique to differentiate between cholesteatomas and granulomas or chronic otitis is not yet available.

Artifacts↗

FAIR and dynamic susceptibility contrast-enhanced perfusion imaging in healthy subjects and stroke patients.

PURPOSE: To compare dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) and the flow-sensitive alternating inversion recovery (FAIR) technique for measuring brain perfusion. MATERIALS AND METHODS: We investigated 12 patients with acute stroke, and 10 healthy volunteers with FAIR and DSC maps of regional cerebral blood volume (rCBV), mean transit time (MTT), and regional cerebral blood flow (rCBF). RESULTS: In volunteers good gray/white-matter contrast was observed in FAIR, rCBF, and rCBV maps. Regions with high signal intensities in FAIR matched well with high values of rCBV and rCBF. In ischemic stroke patients a high correlation (r = 0.78) of the ipsi- to contralateral signal intensity ratios in FAIR and rCBF was observed in areas with perfusion abnormalities. In contrast, FAIR and rCBV (r = 0.50), and FAIR and MTT (r = -0.22) correlated only modestly. Furthermore, FAIR and rCBF demonstrated similar sizes of perfusion abnormality. CONCLUSION: This study demonstrates for the first time that FAIR and rCBF depict similar relations of perfusion in ischemic stroke patients and healthy subjects.

Acute Disease↗

Distribution and course of cortico-respiratory projections for voluntary activation in man. A transcranial magnetic stimulation study in healthy subjects and patients with cerebral ischemia.

The function and course of the cortico-respiratory projections in man are not yet well established. In 30 normal volunteers respiratory muscles were activated by magnetic stimulation of the motor cortex and the cervical and thoracic spinal roots with bilateral recordings from the respiratory muscles. Following cortical stimulation contralateral responses were obtained in all subjects during voluntary inspiration showing a mean latency and amplitude of 13.4+/-1.4ms/1.6+/-1.2 mV (stimulation of the left hemisphere) and 13.2+/-1.3ms/2.5+/-2.5 mV (stimulation of the right hemisphere). Ipsilateral responses were obtained in only 18 (right side) and 21 (left side) subjects and had a significantly (p < 0.001) longer mean latency and lower mean amplitude than the contralateral responses. In 31 patients with impairment of the cortico-respiratory projections due to cerebral infarction demonstrated by magnetic resonance imaging studies, the responsible lesion topography was analysed. We found that, 1. the voluntary activation of respiratory muscles is mediated predominantly by the contralateral motor cortex, 2. the descending cortico-respiratory projections are located within the pyramidal tract, and 3. the cortico-respiratory projections to the respiratory muscles are frequently affected in patients with hemiparesis due to acute stroke. These findings might explain the increased incidence of pneumonia at the hemiparetic side in patients with cerebral ischemia as shown in previous studies.

Adult↗

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia.

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but less than 1 week, suggestive of a reversible ischemic neurological deficit (RIND). Electrophysiological data indicated acute functional brainstem lesions in 54,5 % of patients with transient clinical brainstem impairment. Lesion detection rate was significantly higher when combining electrophysiological data and MRI (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone (39,4 %). We conclude that diffusion weighted MRI and electrophysiological brainstem testing are complimentary sensitive indicators of acute brainstem lesions in patients with reversible neurological deficits. Correct identification of brainstem ischemia influences the therapeutic regimen and may improve patient outcome.

Adult↗

Characterization of BOLD-fMRI signal during a verbal fluency paradigm in patients with intracerebral tumors affecting the frontal lobe.

Previous studies have indicated that the BOLD-fMRI signal can be modified by tumor processes in close vicinity to functional brain areas. This effect has been investigated primarily for the perirolandic area but there is only a limited number of studies concerning frontal cortical regions. Therefore, the aim of the current study was to characterize BOLD-fMRI signal and activation patterns in patients with frontal brain tumors while performing a verbal fluency task. Six patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right sided) intracerebral tumors were examined with fMRI while performing a verbal fluency task in a blocked paradigm design. Eight healthy volunteers served as the control group. The patients (5 right and 1 left handed) demonstrated left frontal activation which could be clearly located outside the tumor area and adjacent edema with varying degrees of additional right frontal activation. In the predominant left frontal activation cluster, the mean voxel based z-score and cluster size were not statistically different between patients and controls. The present fMRI study is indicating that language related BOLD signal changes in the frontal cortex of patients with tumors close to functional areas were comparable to the signal in normal controls. Additionally, the temporal hemodynamic response characteristic was comparable in both groups. This is an important finding consistent with PET results and corroborates the feasibility of functional mapping approaches in patients with tumors affecting the frontal lobe. Additional studies investigating alterations of the hemodynamic response depending on tumor location and histology are required in order to further elucidate the association between pathophysiology and BOLD fMRI signal.

Adult↗

Cerebrovascular brainstem diseases with isolated cranial nerve palsies.

There is a significant number of individual patients with cranial nerve palsies as the sole manifestation of MRI- and, less frequently, CT-documented small brainstem infarctions or hemorrhages. The 3rd and 6th nerves are most commonly involved and, less frequently, the 4th, 5th, 7th, and 8th nerves. An intra-axial basis for such lesions may be underestimated if the diagnosis is based solely on MRI. The electrophysiologic abnormalities indicating brainstem lesions may be independent of MRI-documented morphological lesions. This paper reviews the literature on cerebrovascular brainstem diseases manifesting as isolated cranial nerve palsies. It supports the concept that small pontine and mesencephalic infarctions are the main cause of non-traumatic cranial nerve palsies in the middle-aged and elderly population. Microvascular infarction of the respective extra-axial cranial nerve segments seem to be less important.

Brain Stem↗