Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT.

Brachial plexus root avulsion (BPRA) leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av) treated with normal saline), Av+GM1 (treated with monosialoganglioside), and control. At time points of 3 day (d), 1 week (w), 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.

Neuroimaging to investigate multisystem involvement and provide biomarkers in amyotrophic lateral sclerosis.

Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS). Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS.

Thinning of cervical nerve roots and peripheral nerves in ALS as measured by sonography.

OBJECTIVE: Progressive atrophy and loss of motor axons is a hallmark of amyotrophic lateral sclerosis (ALS). Limited sonographic data are available on potential detection of atrophy of peripheral nerves and nerve roots in ALS. METHODS: Patients with either definite or probable ALS and control subjects underwent sonographic evaluation of the cervical roots (C5, C6, and C7) and peripheral nerves (median and ulnar nerves) on the right. These diameters and cross-sectional areas (C6, median, and ulnar nerves) were compared. RESULTS: The diameters and cross-sectional areas were consistently smaller in ALS than in controls. No correlation was present between the sonographic parameters and the disease severity, disease duration, age, or gender. The overall sensitivity and specificity tended to be greater in the cervical nerve roots than in the peripheral nerves. CONCLUSIONS: This study shows atrophy of cervical nerve roots and peripheral nerves in ALS detected by sonography. Cervical nerve roots might be more appropriate to detect motor axon loss than peripheral nerves. SIGNIFICANCE: Sonographic evaluation of nerve roots and peripheral nerves may be a useful disease marker in ALS to confirm the diagnosis and to potentially monitor the disease progression.

[Utility of muscle ultrasonography for the diagnosis of amyotrophic lateral sclerosis].

The diagnosis of amyotrophic lateral sclerosis (ALS) is frequently challenging, because motor neuron involvement is usually focal at disease onset and many syndromes mimic ALS. Neurological examination and needle EMG are important in the diagnosis of ALS, and patients with early-stage ALS usually undergo several EMG examinations before the diagnosis is confirmed. Ultrasonography has recently been used for the non-invasive assessment of neuromuscular disorders. This review discusses the recent advances in ultrasonography for ALS diagnosis. Ultrasonography could help detect lower motor neuron involvement by evaluating muscle volume, echo intensity, and fasciculations. Previous reports have documented the diagnostic values of all these parameters. In particular, fasciculations are characteristic features of ALS that can be easily and reliably visualized using ultrasonography. Moreover, the combined use of ultrasonography and EMG to detect fasciculations could substantially increase the diagnostic sensitivity of Awaji criteria for ALS. Attempts to utilize ultrasonography for ALS diagnosis have started only recently, and the technique used is yet to be standardized. However, ultrasonography has a major advantage over EMG in that it is non-invasive. Further studies are needed to understand the use of ultrasound as a novel non-invasive tool for ALS diagnosis.

A 3-dimensional digital atlas of the ascending sensory and the descending motor systems in the pigeon brain.

Pigeons are classic animal models for learning, memory, and cognition. The majority of the current understanding about avian neurobiology outside of the domain of the song system has been established using pigeons. Since MRI represents an increasingly relevant tool for comparative neuroscience, a 3-dimensional MRI-based atlas of the pigeon brain becomes essential. Using multiple imaging protocols, we delineated diverse ascending sensory and descending motor systems as well as the hippocampal formation. This pigeon brain atlas can easily be used to determine the stereotactic location of identified neural structures at any angle of the head. In addition, the atlas is useful to find the optimal angle of sectioning for slice experiments, stereotactic injections and electrophysiological recordings. This pigeon brain atlas is freely available for the scientific community.

Single motor unit recordings in human geniohyoid reveal minimal respiratory activity during quiet breathing.

Maintenance of airway patency during breathing involves complex interactions between pharyngeal dilator muscles. The few previous studies of geniohyoid activity using multiunit electromyography (EMG) have suggested that geniohyoid shows predominantly inspiratory phasic activity. This study aimed to quantify geniohyoid respiration-related activity with single motor unit (SMU) EMG recordings. Six healthy subjects of normal body mass index were studied. Intramuscular EMG recordings of geniohyoid activity were made with a monopolar needle with subjects in supine and seated positions. The depth of the geniohyoid was identified by ultrasound, and the electrode position was confirmed with maneuvers to isolate activity in geniohyoid and genioglossus. Activity was recorded at 85 sites in the geniohyoid during quiet breathing (45 supine and 40 seated). When subjects were supine, 33 sites (73%) showed no activity during breathing and 10 (22%) showed tonic activity. In addition, one site showed a tonic SMU with increased expiratory discharge, and one site in another subject had one unit with expiratory phasic activity. When subjects were seated, 27 sites (68%) in the geniohyoid showed no activity, 12 sites (30%) showed tonic activity that was not respiration related, and one unit at one site showed phasic expiratory activity. The average peak discharge frequency of geniohyoid motor units was 16.2 ± 3.1 impulses/s during the "geniohyoid maneuver," which was the first part of a swallow. In contrast to previous findings, the geniohyoid shows some tonic activity but minimal respiration-related activity in healthy subjects in quiet breathing. The geniohyoid has little active role in airway stability under these conditions.

The diagnostic value of ultrasonography in patients with electrophysiologicaly confirmed carpal tunnel syndrome.

OBJECTIVE: To evaluate the diagnostic value of ultrasonography in patients with electrophysiologically confirmed carpal tunnel syndrome. DESIGN: A prospective ultrasonographic study of 70 wrists with electrophysiologically confirmed carpal tunnel syndrome and of 80 normal wrists. Receiver-operating-characteristics curves for the ultrasonographic measurements of median nerve were plotted to identify the most optimal cutoff values. RESULTS: The ultrasonographic measurements of median nerves were found to be increased significantly in patients with carpal tunnel syndrome when compared with controls, particularly in terms of cross-sectional area (P <0.001). According to receiver-operating-characteristics curve results, the most optimal cutoff value for the cross-sectional area of the median nerve was obtained at the level of middle carpal tunnel, which was 9.3 mm2, with a sensitivity of 80% and specificity of 77.5%. CONCLUSION: Ultrasonographic examination of the median nerve seems to be a promising method in the diagnosis of carpal tunnel syndrome, evaluating the morphologic changes of the median nerve in patients with clinical signs and symptoms. Further studies with wider series are needed to confirm our preliminary results.

Ultrasound guidance with nerve stimulation reduces the time necessary for resident peripheral nerve blockade.

BACKGROUND AND OBJECTIVES: Educating residents in peripheral nerve blockade may impact the efficiency of a busy regional anesthesia service. Ultrasound guidance may affect the efficiency and effectiveness of nerve block. We examined the impact of ultrasound guidance on resident performance of peripheral nerve block in a regional anesthesia rotation. METHODS: An existing de-identified database was used for retrospective analysis of resident performance of interscalene, axillary, femoral, and popliteal nerve blocks, by peripheral nerve stimulator guidance alone and by nerve stimulator aided by ultrasound. The primary variable examined was the time required to perform the block. Others variables included (1) number of needle insertions; (2) proportion of blocks in which there was a blood vessel puncture; and (3) block efficacy. Peripheral nerve-stimulator blocks were guided by surface anatomy and motor stimulation, refined to 0.2 to 0.5 mA of current before injection of local anesthetic, while ultrasound nerve stimulator blocks were confirmed using a current of 0.5 mA. RESULTS: Ultrasound-aided blocks required less time to perform (median = 1.8 min) than nerve stimulator-guided blocks (median = 6.5 min, P < .001). More needle insertions were required for nerve localization in the nerve stimulator-guided blocks (median = 6) than in ultrasound-aided blocks (median = 2; P < .001). There were fewer blood vessel punctures with ultrasound-aided blocks (P = .03). CONCLUSIONS: During resident teaching, ultrasound-aided peripheral nerve-stimulated block required less time to perform than did nerve-stimulator-guided blocks. Fewer needle insertions were required to perform the ultrasound-guided blocks, and there were fewer blood vessel punctures when ultrasound was used.

Ultrasound-guided interscalene needle placement produces successful anesthesia regardless of motor stimulation above or below 0.5 mA.

BACKGROUND: We quantified the motor response after ultrasound (U-S)-guided needle placement for interscalene block (ISB). We then compared block characteristics based on motor response above or below 0.5 mA. METHODS: Sixty-one patients scheduled for ambulatory shoulder surgery under ISB and general anesthesia were included in this prospective, observational study. Preoperatively, an insulated needle was positioned by U-S in the interscalene groove. The lowest current producing motor response was determined, and 30 mL 0.5% bupivacaine with epinephrine was injected. Motor and sensory block were tested in the upper trunk distribution for 15 min until general anesthesia was induced. Postoperatively, the success of upper trunk block, pain score in the postanesthesia care unit and block duration, and analgesic tablet consumption overnight were recorded. Patients were divided a priori into Group A (current < or =0.5 mA) and Group B (current >0.5 mA), and results were compared between groups. RESULTS: The observed current range was 0.14-1.7 mA, with current < or =0.5 mA in 42% of patients (Group A). All patients had complete sensorimotor upper trunk block and none required narcotics in the postanesthesia care unit. Block duration (both groups: 17.8 +/- 4.9 h, mean +/- sd) and home analgesic use were equivalent. Sensory block onset was equivalent between groups, but incomplete motor block at 15 min was more likely in Group B: 37% vs 12% in Group A (P = 0.03). CONCLUSION: During U-S-guided ISB using nerve stimulation, the observed motor response below or above 0.5 mA had no impact on success or duration of upper trunk block.

Sources of porcine longissimus dorsi muscle (LDM) innervation as revealed by retrograde neuronal tract-tracing.

The aim of the present study was to establish the origin of the motor, autonomic and sensory innervation of the L1-L2 segment of the porcine longissimus dorsi muscle (LDM), in order to provide morphological basis for further studies focusing on this neural pathway under experimental conditions, e.g. phototerapy and/or lateral electrical surface stimulation. To reach the goal of the study, multiple injections of the fluorescent neuronal tracer Fast Blue (FB) were made into the LDM region between the spinal processes of the vertebrae L1 and L2. The spinal cord (Th13-S1 segments) as well as the sensory and autonomic ganglia of interest, i.e., dorsal root (DRG) and sympathetic chain ganglia from corresponding spinal cord levels were collected three weeks later. FB-positive (FB+) motoneurons were observed exclusively within the nucleus ventromedialis at L1 and L2 spinal cord level, forming the most ventro-medially arranged cell column within this nucleus. Primary sensory and sympathetic chain neurons were found in appropriate ipsilateral ganglia at Th15-L3 levels. The vast majority of retrogradely traced neurons (virtually all motoneurons, approximately 76% of sensory and 99.4% of sympathetic chain ganglia neurons) was found at the L1 and L2 levels. The morphometric evaluation of FB-labeled DRG neurons showed that the majority of them (approximately 66%) belonged to the class of small-diameter perikarya (10-30 microm in diameter), whereas those of medium size (30-80 microm in diameter) and of large diameter (more than 80 microm) constituted 22.6% and 11.5% of all DRG neurons, respectively. The results of the present study demonstrated that the nerve terminals supplying porcine LDM originated from different levels of the spinal cord, dorsal root and sympathetic chain ganglia. Thus, the study has revealed sources and morphological characteristic of somatic, autonomic and spinal afferent neurons supplying porcine LDM, simultaneously pointing out the characteristic features of their distribution pattern.

Sensory and motor function of the esophagus: lessons from ultrasound imaging.

Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal sensory and motor function and dysfunction in vivo in humans. It can be combined with manometry, pH, and impedance measurement techniques to determine the relationships between different physiologic parameters. High-frequency intraluminal ultrasound imaging has provided a number of important insights regarding the longitudinal muscle function of the esophagus. On the basis of the ultrasound images and intraluminal pressure recordings, it seems that there is synchrony in the timing and the amplitude of contraction between the circular and longitudinal muscle layers. A sustained contraction of the longitudinal muscle layer is temporally related to esophageal chest pain and heartburn. The biomechanics of the esophageal wall and its relationship to sensory and motor function can be studied in humans in vivo by using high-frequency intraluminal ultrasound much more precisely than has previously been possible. Achalasia, diffuse esophageal spasm, and nutcracker esophagus are associated with hypertrophy of circular and longitudinal muscle layers. Finally, high-frequency intraluminal ultrasound imaging is the only technique that can detect reflux-related distention of the esophagus and its role in esophageal symptoms. Future approaches to display and quantify ultrasound image data are discussed. The principles of high-frequency intraluminal ultrasound described here are also applicable to study of the motor and sensory function of the other regions of the gastrointestinal tract.

New methods for the computer-assisted 3-D reconstruction of neurons from confocal image stacks.

Exact geometrical reconstructions of neuronal architecture are indispensable for the investigation of neuronal function. Neuronal shape is important for the wiring of networks, and dendritic architecture strongly affects neuronal integration and firing properties as demonstrated by modeling approaches. Confocal microscopy allows to scan neurons with submicron resolution. However, it is still a tedious task to reconstruct complex dendritic trees with fine structures just above voxel resolution. We present a framework assisting the reconstruction. User time investment is strongly reduced by automatic methods, which fit a skeleton and a surface to the data, while the user can interact and thus keeps full control to ensure a high quality reconstruction. The reconstruction process composes a successive gain of metric parameters. First, a structural description of the neuron is built, including the topology and the exact dendritic lengths and diameters. We use generalized cylinders with circular cross sections. The user provides a rough initialization by marking the branching points. The axes and radii are fitted to the data by minimizing an energy functional, which is regularized by a smoothness constraint. The investigation of proximity to other structures throughout dendritic trees requires a precise surface reconstruction. In order to achieve accuracy of 0.1 microm and below, we additionally implemented a segmentation algorithm based on geodesic active contours that allow for arbitrary cross sections and uses locally adapted thresholds. In summary, this new reconstruction tool saves time and increases quality as compared to other methods, which have previously been applied to real neurons.

Amyotrophic lateral sclerosis and primary lateral sclerosis: evidence-based diagnostic evaluation of the upper motor neuron.

Magnetic resonance imaging and MR spectroscopy are important tools in the diagnostic evaluation of patients with suspected motor neuron disease. Further investigation is needed to determine and to compare the utility of various neuroimaging markers for diagnosis and disease progression [112]. Newer MR tools, such as diffusion tensor imaging, magnetization transfer imaging, and functional MR imaging, have substantial promise as scientific and clinical tools in this ongoing endeavor.

Brainstem dysgenesis: report of five patients with congenital hypotonia, multiple cranial nerve involvement, and ocular motor apraxia.

This paper reports three females and two males with a distinctive congenital syndrome characterized by severe congenital hypotonia, facial diplegia, jaw ankylosis, velo-pharyngeal incoordination, pyramidal tract signs, and ocular motor apraxia. Patients were followed up at ages ranging from 20 months to 16 years. All cases of this syndrome are sporadic, without dysmorphological features, chromosomal, or MRI brain abnormalities. Electrophysiological studies indicate the brainstem as the site of the neurological dysfunction. Post-mortem CNS study of one of the patients demonstrated neuronal depletion of the IV, VII, VIII, and IX cranial nerve nuclei and intact morphology of the cerebral hemispheres. A vascular accident, early in foetal life, is the most likely cause of the clinical picture. The extent of brainstem involvement and its related clinical findings distinguishes these patients from those with Moebius, Pierre Robin, or Cogan syndromes. Outcome is better than what could be anticipated during the first few months of life given the severity of symptoms. Intelligence or developmental quotients are within the normal range for their age. Facial hypomimia, feeding, and speech articulatory performance difficulties are the main disabilities observed in these patients at follow-up.

Preoperative motor system brain mapping using positron emission tomography and statistical parametric mapping: hints on cortical reorganisation.

OBJECTIVES: This study investigated the applicability of statistical parametric mapping (SPM) for analysing individual preoperative brain mapping studies in patients with cerebral mass lesions for neurosurgical planning. The study further investigated if hints on functional reorganisation processes can be found. METHODS: Nine adult patients with cerebral mass lesions underwent activation [(15)O]water-PET under stimulation by finger (n=9) and foot (n=4) movement. Individual SPM-t-maps were computed without anatomical normalisation and coregistered to the individual magnetic resonance imaging. Relative cerebral blood flow change maps were calculated for comparison. RESULTS: The spatial relation between the sensorimotor cortex and the lesion could be determined in all cases. Additional activations covered the ipsilateral sensorimotor cortex and the bilateral cerebellum, premotor cortices and supplementary motor areas. Patients with motor symptoms of the stimulated hand (paresis, focal seizures) activated the ipsilateral premotor cortices and contralateral cerebellum more often than patients without motor symptoms. The SPM results for p<0.005 and cerebral blood flow change maps showed considerably overlapping motor area activations. For p<0.001, SPM missed three sensorimotor cortex activations depicted by cerebral blood flow change maps and by SPM for p<0.005 in typical localisation. SPM analyses showed less activations probably unrelated to task performance. CONCLUSION: It is concluded that SPM provides an efficient method for analysing individual preoperative PET activation studies. Activations of the ipsilateral premotor cortices and contralateral cerebellum may indicate an enhanced recruitment of ipsilateral motor pathways evoked by functional reorganisation processes. However, this changed activation pattern was not necessarily associated with a better neurological status.

MRI and SPECT findings in amyotrophic lateral sclerosis. Demonstration of upper motor neurone involvement by clinical neuroimaging.

MRI was performed in 21 patients and single photon emission computed tomography (SPECT) with N-isopropyl-p-123I iodoamphetamine in 16 patients, to visualize upper motor neurone lesions in amyotrophic lateral sclerosis. T2-weighted MRI revealed high signal along the course of the pyramidal tract in the internal capsule and cerebral peduncle in 4 of 21 patients. SPECT images were normal in 4 patients, but uptake was reduced in the cerebral cortex that includes the motor area in 11.

Regional cerebral blood flow study with 123I-IMP in patients with degenerative dementia.

Regional cerebral blood flow was evaluated by single-photon emission CT (SPECT) with 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) in 11 patients with dementia of the Alzheimer type, three patients with progressive dementia and motor neuron disease, and eight healthy control subjects. Regional blood flow measurements in the bilateral frontal, parietal association, and temporal cortices were lower in the Alzheimer dementia patients than in controls. Flow deficits in the parietal association cortex were demonstrated in all patients with Alzheimer-type dementia; these deficits were correlated with the severity of disease. Lateral hemispheric asymmetry was seen in nine of 11 patients with Alzheimer-type dementia. In all three patients with progressive dementia and motor neuron disease, flow deficits were demonstrated in the bilateral frontal and temporal cortices, but no flow deficits were seen in the parietal association cortex. Brain SPECT with 123I-IMP may be useful in the differential diagnosis and evaluation of the severity of degenerative dementia.

[Localization of the rabbit pharyngeal motoneurons and peripheral courses of their axons: a study by means of the retrograde HRP or fluorescent labeling technique].

The localization of the rabbit pharyngeal montoneurons in the nucleus ambiguus and peripheral courses of their axons were investigated using injection of retrograde labeling tracers, i.e., HRP and nuclear yellow, into the individual pharyngeal muscles or using the injection in conjunction with intracranial severing of either the vagal or glossopharyngeal rootlets. The nucleus ambiguus of the rabbit was divided into four groups of neuron, of which the following two, the compact cell group (CoG) and the medial scattered group (SGm), were pertinent to the pharyngeal montoneurons. The CoG is a group formed by a compact arrangement of the smallest neurons and situated in the rostral half of the nucleus ambiguus. The SGm is a group formed by a scattered arrangement of slightly larger neurons in the rostral one-third of the nucleus and located medial to the CoG. The labeled stylopharyngeal motoneurons occupied the rostral portion of the SGm at a level from about 2800 to 3100 microns rostral to the obex. They were completely abolished by severing the glossopharyngeal rootlets, in contrast to no change of labeled neuron number when severing the vagal rootlets. Thus, all axons of the stylopharyngeal motoneurons were concluded to traverse the glossopharyngeal rootlets. The labeled palatopharyngeal motoneurons were found in the caudal portion of the CoG at a level from 500 to 1900 microns rostral to the obex, with their number being numerous at the caudal one-third of CoG, 500 to 1300 microns. All their axons traversed the vagal rootlets. The labeled pharyngeal constrictor motoneurons were found at almost all rostrocaudal levels of CoG, 500 to 2900 microns rostral to the obex, with their number being numerous in its middle one-third level. Although motoneurons of the superior constrictor, those of the middle constrictor, and those of the thyro and cricopharyngeal muscles composing the inferior constrictor overlapped rostrocaudally in location, their ranges of appearance had a tendency of arranging rostrocaudally in that order. At the middle one-third level of CoG, in which the CoG was subdivided into two subgroups, dorsomedial and ventrolateral, the superior and middle constrictor motoneurons were located in its entire portion. The majority of axons of the pharyngeal constrictor motoneurons traversed the vagal rootlets, though a few axons whose somata lay in the rostral portion of the CoG traversed the glossopharyngeal rootlets.

A potential screening technique for neurotransmitters in the CNS: model studies in the cat spinal cord.

This paper describes a potential screening technique for neurotransmitters in the CNS. The method uses the injection of small volumes of high specific activity radioactive transmitter precursor substances into regions of physiologically identified neuronal cell bodies, and the later identification of the substances transported down axons to target tissues. Experiments were performed in motoneurons in the cat spinal cords to test the feasibility of method. Tritiated choline, glutamate, tyramine and tryptophan were pressure-injected into the ventral horn using glass micropipettes that were adapted to allow similtaneous physiological recording and injection. Only tritiated acetylcholine, two unidentified choline metabolites and a small amount of choline were found in the motor axons. The acetylcholine migrated at a rate of greater than 24mm/day and the movement was blocked by colchicine. The spread of isotope from the injection site was measured by a direct chemical method and by autoradiography, and was found that isotope spread1-2 mm from the injection site. One unexpected finding in the autoradiographs was that the motoneurons were selectively labelled following choline injections.