Nerve ultrasound as follow-up tool in treated multifocal motor neuropathy.

BACKGROUND AND PURPOSE: High-resolution ultrasound is a valuable tool in supporting the diagnosis of multifocal motor neuropathy (MMN) but longitudinal data under therapy are lacking. METHODS: The change in peripheral nerve ultrasound pattern in patients with MMN was assessed over time. Patients with MMN received a thorough initial examination and follow-up over a period of 6-12 months using high-resolution ultrasound of the cervical roots and the nerves of the arms and legs, nerve conduction studies, Medical Research Council Sum Score (MRCSS) and Rotterdam Inflammatory Neuropathy Cause and Treatment Group (INCAT) score to evaluate changes under treatment. The Ultrasound Pattern Sum Score (UPSS) was used as standardized peripheral nerve ultrasound protocol. RESULTS: Seventeen patients with MMN received initial examinations of whom 12 were successfully followed up. All patients with MMN showed at least localized but often multifocal peripheral nerve enlargement. An enlarged overall cross-sectional area as well as enlarged single fascicles (>3 mm²) in clinically and electrophysiologically affected (>90%) and unaffected (>70%) nerves were found. The UPSS did not correlate with clinical disability at both visits. However, the change in clinical disability (evaluated as difference in MRCSS) and the change in UPSS correlated significantly inversely (P = 0.004). CONCLUSIONS: High-resolution sonography of peripheral nerves revealed multifocal nerve enlargement in MMN. Distinct enlargement patterns may support the diagnosis. Ultrasound findings did not correlate well with clinical severity or electrophysiological findings at initial presentation. As changes in UPSS correlated significantly with the clinical course in terms of muscle strength (MRCSS), sonographic assessment may represent a useful tool for therapeutic monitoring.

Muscle ultrasonography as an additional diagnostic tool for the diagnosis of amyotrophic lateral sclerosis.

OBJECTIVE: We aimed to determine the utility of muscle ultrasonography (MUS) in addition to electromyography (EMG) in the diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: In all, 60 patients with ALS and 20 with other neuromuscular disorders underwent MUS and EMG. In addition, 30 healthy controls underwent only MUS. Occurrence of fasciculations and fibrillations was evaluated. Ultrasonic echogenicity was graded semiquantitatively. RESULTS: The incidence of fasciculations was significantly higher in patients undergoing MUS than in those undergoing EMG (p<0.05), even in muscles of full strength (p<0.001). However, EMG was more sensitive in detecting fibrillations (p<0.05). MUS had an overall higher sensitivity in detecting spontaneous activity in the tongue (p<0.05). Patients with ALS showed significantly increased muscle echo intensity (EI) compared to patients who were initially suspected as having ALS and normal controls (p<0.05), irrespective of the clinical or electrophysiological status. CONCLUSION: Our results showed that the sensitivity and specificity of MUS in diagnosing ALS was almost equivalent to those of EMG, using the Awaji criteria. Combination of MUS and EMG enhances the diagnostic accuracy compared to EMG alone (p<0.05). SIGNIFICANCE: The combination of EMG and MUS can be used to evaluate the lower motor neuron affection by reducing the use of the often painful and uncomfortable EMG examinations but without decreasing the diagnostic sensitivity and specificity.

[Neurological and psychological long-term effects of sepsis]. / Neurologische und psychische Langzeitfolgen der Sepsis.

BACKGROUND: In addition to the limitations to the health-related quality of life that have been compiled with validated test instruments, a number of former sepsis patients suffer from functional impairments, which are categorized under the terms critical illness polyneuropathy (CIP) or critical illness myopathy (CIM), which have been in existence for over 20 years now. CURRENT FOCUS: The issues of delirium during intensive therapy and persistent residual neurocognitive impairments, posttraumatic stress disorder (PTSD) and states of depression related to perihospital functional development have increasingly attracted notice. FUTURE: The degree of functional deficits resulting from sepsis and the actual quality of life of those affected may, however, be influenced by taking appropriate rehabilitation measures. However, neither therapeutic rehabilitation standards nor any rehabilitation facilities tailored to the needs of these patients currently exist.

[Dysphagia management of acute and long-term critically ill intensive care patients]. / Dysphagie-Management im Akut- und Langzeitverlauf bei kritisch kranken intensivpflichtigen Patienten.

Dysphagia is a severe complication in critically ill patients and affects more than half the patients in an intensive care unit. Dysphagia also has a strong impact on morbidity and mortality. Risk factors for the development of dysphagia are neurological diseases, age >55-70 years, intubation >7 days and sepsis. With increasing numbers of long-term survivors chronic dysphagia is becoming an increasing problem. There is not much knowledge on the influence of specific diseases, including the direct impact of sepsis on the development of dysphagia. Fiberoptic evaluation of swallowing is a standardized tool for bedside evaluation, helping to plan swallowing training during the acute phase and to decrease the rate of chronic dysphagia. For evaluation of chronic dysphagia even more extensive diagnostic tools as well as several options of stepwise rehabilitation using restitution, compensation and adaption strategies for swallowing exist. Currently it seems that these options are not being sufficiently utilized. In general, there is a need for controlled clinical trials analyzing specific swallowing rehabilitation concepts for former critically ill patients and long-term survivors.

[Critical illness polyneuropathy and critical illness myopathy]. / Critical-Illness-Polyneuropathie und Critical-Illness-Myopathie.

Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are frequent complications in critically ill patients and both are associated with sepsis, systemic inflammatory response syndrome (SIRS) and multiorgan failure. Major signs are muscle weakness and problems of weaning from the ventilator. Both CIP and CIM lead to elongated times of ventilation, elongated hospital stay, elongated times of rehabilitation and increased mortality. Electrophysiological measurements help to detect CIP and CIM early in the course of the disease. State of the art sepsis therapy is the major target to prevent the development of CIP and CIM. Although no specific therapy of CIP and CIM has been established in the past, the diagnosis generally improves the therapeutic management (weaning from the ventilator, early physiotherapy, etc.). This review provides an overview of clinical and diagnostic features of CIP and CIM and summarizes current pathophysiological and therapeutic concepts.

[Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus]. / Familiäre Alzheimer-Variante mit Amyloidangiopathie als Ausdruck einer APP-Gen-Duplikation.

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

Initial DWI and ADC imaging may predict outcome in acute disseminated encephalomyelitis: report of two cases of brain stem encephalitis.

Two young patients with acute disseminated encephalomyelitis (ADEM) of the brain stem are described. In spite of similar lesion sites in the brain stem, reaching from the upper medulla to the mesencephalon, the outcomes of the patients were very different: one made a full clinical recovery within three weeks while the other remained in a locked-in state more than a year after the disease episode. Both patients also differed in magnetic resonance imaging (MRI) findings on admission. The patient who remained in a locked-in state had pathological diffusion weighted imaging (DWI) scans and decreased apparent diffusion coefficient maps initially, with severe tissue destruction on follow up computed tomography, while the patient who recovered fully showed initially increased apparent diffusion coefficient values and almost complete resolution of MRI changes on follow up. Thus a comparison of these two cases may indicate differences in the underlying pathology in ADEM (vasogenic v cytotoxic oedema) that may be crucial for estimating tissue damage and clinical outcome.

[Procalcitonin as a marker for severe sepsis in an immunosuppressed patient]. / Procalcitonin als Marker der schweren Sepsis bei einer immunsupprimierten Patientin.

A 22 year old female was admitted to the emergency department with high fever up to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she presented with bilateral pulmonary coarse crackles. Diagnosis on admission was pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased early, reaching up to 435 ng/mL, while C-reactive protein levels were only moderately increased, with several days delay. The sepsis was originated from a multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT levels reflected the severity of septic shock in that it paralleled noradrenaline demand. Ten months previously, the patient had been diagnosed with acute disseminated brainstem encephalitis (ADEM), and had received two cycles of intravenous cyclophosphamide. Our case illustrates that PCT is an early marker for sepsis and it indicates that PCT may also be a valuable marker for the severity of sepsis in immunosuppressed patients.

Localization of cGMP-dependent protein kinase type II in rat brain.

In brain, signaling pathways initiated by atrial natriuretic peptide, or transmitters which stimulate nitric oxide synthesis, increase cGMP as their second messenger. One important class of target molecules for cGMP is cGMP-dependent protein kinases, and in the present study, biochemical and immunocytochemical analyses demonstrate the widespread distribution of type II cGMP-dependent protein kinase in rat brain, from the cerebral cortex to the brainstem and cerebellum. Also, colocalization of cGMP-dependent protein kinase type II with its activator, cGMP, was found in several brain regions examined after in vitro stimulation of brain slices with sodium nitroprusside. In western blots, cGMP-dependent protein kinase type II was observed in all brain regions examined, although cerebellar cortex and pituitary contained comparatively less of the kinase. Immunocytochemistry revealed cGMP-dependent protein kinase type II in certain neurons, and occasionally in putative oligodendrocytes and astrocytes, however, its most striking and predominant localization was in neuropil. Electron microscopy examination of neuropil in the medial habenula showed localization of the kinase in both axon terminals and dendrites. As a membrane-associated protein, cGMP-dependent protein kinase type II often appeared to be transported to cell processes to a greater extent than being retained in the cell body. Thus, immunocytochemical labeling of cGMP-dependent protein kinase type II often did not coincide with the localization of kinase mRNA previously observed by others using in situ hybridization. We conclude that in contrast to cGMP-dependent protein kinase type I, which has a very restricted localization to cerebellar Purkinje cells and a few other sites, cGMP-dependent protein kinase type II is a very ubiquitous brain protein kinase and thus a more likely candidate for relaying myriad cGMP effects in brain requiring protein phosphorylation.

Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle.

Human GLUT11 (encoded by the solute carrier 2A11 gene, SLC2A11) is a novel sugar transporter which exhibits significant sequence similarity with the members of the GLUT family. The amino acid sequence deduced from its cDNAs predicts 12 putative membrane-spanning helices and all the motifs (sugar-transporter signatures) that have previously been shown to be essential for sugar-transport activity. The closest relative of GLUT11 is the fructose transporter GLUT5 (sharing 41.7% amino acid identity with GLUT11). The human GLUT11 gene (SLC2A11) consists of 12 exons and is located on chromosome 22q11.2. In human tissues, a 7.2 kb transcript of GLUT11 was detected exclusively in heart and skeletal muscle. Transfection of COS-7 cells with GLUT11 cDNA significantly increased the glucose-transport activity reconstituted from membrane extracts as well as the specific binding of the sugar-transporter ligand cytochalasin B. In contrast to that of GLUT4, the glucose-transport activity of GLUT11 was markedly inhibited by fructose. It is concluded that GLUT11 is a novel, muscle-specific transport facilitator that is a member of the extended GLUT family of sugar/polyol-transport facilitators.

In vivo 3D visualization of normal pyramidal tracts in human subjects using diffusion weighted magnetic resonance imaging and a neuronavigation system.

We describe the potential of anisotropic diffusion weighted imaging to visualize the course of large cerebral fiber tracts. Five healthy volunteers were investigated at a field strength of 1.5 Tesla, employing a spin-echo diffusion weighted sequence with gradient sensitivity in six non-collinear directions to visualize the course of the pyramidal tracts. The pyramidal tracts were segmented and reconstructed for three-dimensional visualization. Reconstruction results together with a fusioned high resolution 3D T1 weighted image data set were available in a customized neuronavigation system. Origination in the primary motor cortex, convergence in the centrum semiovale, the posterior limb of the internal capsule, the cerebral peduncles, the splitting at the level of the pons, and the pyramidal decussation were identified in all subjects. Fiber tract maps might have the prospect of guiding neurosurgical interventions, especially when being linked to a neuronavigation system. Other potential applications include the demonstration of the anatomical substrate of functional connectivity in the human brain.

Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain.

Nitric oxide (NO)-mediated cGMP synthesis is localized throughout the rat brain in close proximity to the NO-synthase-containing structures. However, characterization of the cGMP synthesizing structures in terms of co-localization with the classical neurotransmitter systems has not yet been reported. Here we present evidence, using double immunostaining for cGMP and the vesicular acetylcholine transporter, that virtually all of the cholinergic fibers in the cerebral cortex and the majority of the cholinergic fibers in the basal ganglia accumulate cGMP in response to a NO donor. In these areas, only few cGMP-containing fibers were observed not to be part of the cholinergic system. Co-localization between cGMP and the vesicular acetylcholine transporter was only observed to a minor degree in the ventral forebrain, the hippocampus, the reticular thalamic nucleus, and the nucleus ambiguus. No association of cGMP synthesis with the cholinergic system was observed to a similar extent in other brain areas. These results, in combination with literature data on the distribution of cholinergic receptors in the rat brain, suggest that NO has an anterograde and/or retrograde signaling function on subsets of cholinergic neurons.

Collagen fibers in linea alba and rectus sheaths.

BACKGROUND: After the description of a general scheme of the architecture of collagen fibers in linea alba and rectus sheaths, variability and differences of fiber architectures were analyzed to describe their functional role. MATERIALS AND METHODS: Using confocal laser scanning microscopy the diameter of each layer of fibril bundles was measured in linea alba and rectus sheaths of 12 human cadavers, and each fibril bundle was classified according to its orientation (oblique I and II, transverse). RESULTS: The mean diameter of fibril bundles in the supraumbilical region of the linea alba was smaller than in the infraumbilical region, and in the supraumbilical region the thickness of the linea alba was smaller than in the infraumbilical region. Analyzing sex-dependent differences in the fiber architecture of the linea alba, a larger amount of transverse fibers relative to oblique fibers were found in females in infraumbilical regions. The thickness of the infraumbilical linea alba was smaller in females than in males, while its width was larger. CONCLUSIONS: There exist gender differences in the architecture of the linea alba. However, whether these morphological differences demonstrate the adaptability of this fiber architecture to biomechanical stress in raised intraabdominal pressure in pregnancy remains to be proven. The transverse fibers act as a counterpart to the intraabdominal pressure whereas the oblique fibers are involved mainly in movements of the trunk.

Supra- and infrasylvian conduction aphasia.

Fifteen cases of conduction aphasia which were tested with the Aachen Aphasia Test (AAT), are presented. The CT lesion data were transformed to a standard 3D-reference brain referring to the ACPC line. According to the lesion profiles a group of 6 patients had pure suprasylvian lesions, a group of 4 patients had pure infrasylvian lesions, and a group of 5 patients had lesions in both supra- and infrasylvian regions. Suprasylvian conduction aphasics are superior to infrasylvian conduction aphasics in the token test and in repetition tasks. Infrasylvian conduction aphasics use more stereotypes in spontaneous speech than suprasylvian conduction aphasics. Conduction aphasics with both lesion sites perform less well in tests of naming, writing, and comprehension than the pure types. Thus conduction aphasia is a heterogeneous syndrome anatomically and linguistically.

Quantitative estimation of 3-D fiber course in gross histological sections of the human brain using polarized light.

Series of polarized light images can be used to achieve quantitative estimates of the angles of inclination (z-direction) and direction (in xy-plane) of central nervous fibers in histological sections of the human brain. (1) The corpus callosum of a formalin-fixed human brain was sectioned at different angles of inclination of nerve fibers and at different thicknesses of the samples. The minimum, and maximum intensities, and their differences revealed a linear relationship to the angle of inclination of fibers. It was demonstrated that sections with a thickness of 80--120 microm are best suited for estimating the angle of inclination. (2) Afterwards the optic tracts of eight formalin-fixed human brains were sliced at different angles of fiber inclination at 100 microm. Measurements of intensity in 30 pixels in each section were used to calculate a linear function of calibration. The maximum intensities and the differences between maximum and minimum values measured with two polars only were best suited for estimation of fiber inclination. (3) Gross histological brain slices of formalin-fixed human brains were digitized under azimuths from 0 to 80 degrees using two polars only. These sequences were used to estimate the inclination of fibers (in z-direction). The same slices were digitized under azimuths from 0 to 160 degrees in steps of 20 degrees using a quarter wave plate additionally. These sequences were used to estimate the direction of the fibers in xy-direction. The method can be used to produce maps of fiber orientation in gross histological sections of the human brain similar to the fiber orientation maps derived by diffusion weighted magnetic resonance imaging.

Collagen fibers in linea alba and rectus sheaths. I. General scheme and morphological aspects.

BACKGROUND: The anatomy of the anterior abdominal wall plays a most significant role in surgery. Thus the three-dimensional architecture of the collagen fibers in linea alba and rectus sheaths was investigated in 12 human cadavers. MATERIAL AND METHODS: The linea alba was divided into 14 different anatomical segments in the craniocaudal direction. Two-hundred-micrometer-thick, eosin-stained sections from these segments were analyzed by confocal laser scanning microscopy. In this way the direction of the collagen fibers was estimated in the midline of the linea alba and in the medial parts of the rectus sheaths. Width and thickness of the linea alba and thickness of the rectus sheaths were measured. RESULTS: In the ventral rectus sheath essentially oblique fibril bundles intermingle with each other, while the dorsal rectus sheath consists chiefly of transverse fibril bundles. In the linea alba three different zones of fiber orientation follow each other from ventral to dorsal: The lamina fibrae obliquae consists of intermingling oblique fibers. The lamina fibrae transversae contains mainly transverse fibril bundles, while an inconstant, small lamina fibrae irregularium is composed of oblique fibers. Different regions can be distinguished in the craniocaudal course of the linea alba: supraumbilical part, umbilical part, transition zone, and infraarcuate part. CONCLUSIONS: A new model of fiber architecture of the linea alba was developed that describes the fiber architecture as a three-dimensional, highly structured meshwork of collagen fibers. In contrast to former models, no separate lines of decussation of the fibers could be found.