Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment.

BACKGROUND: Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DESIGN: Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (

Neurovascular Interactions in the Nervous System.

Molecular cross talk between the nervous and vascular systems is necessary to maintain the correct coupling of organ structure and function. Molecular pathways shared by both systems are emerging as major players in the communication of the neuronal compartment with the endothelium. Here we review different aspects of this cross talk and how vessels influence the development and homeostasis of the nervous system. Beyond the classical role of the vasculature as a conduit to deliver oxygen and metabolites needed for the energy-demanding neuronal compartment, vessels emerge as powerful signaling systems that control and instruct a variety of cellular processes during the development of neurons and glia, such as migration, differentiation, and structural connectivity. Moreover, a broad spectrum of mild to severe vascular dysfunctions occur in various pathologies of the nervous system, suggesting that mild structural and functional changes at the neurovascular interface may underlie cognitive decline in many of these pathological conditions.

Microvascular networks in the area of the auditory peripheral nervous system.

Using transgenic fluorescent reporter mice in combination with an established tissue clearing method, we detail heretofore optically opaque regions of the spiral lamina and spiral limbus where the auditory peripheral nervous system is located and provide insight into changes in cochlear vascular density with ageing. We found a relatively dense and branched vascular network in young adults, but a less dense and thinned network in aged adults. Significant reduction in vascular density starts early at the age of 180 days in the region of the spiral limbus (SL) and continues into old age at 540 days. Loss of vascular volume in the region of spiral ganglion neurons (SGN) is delayed until the age of 540 days. In addition, we observed that two vascular accessory cells are closely associated with the microvascular system: perivascular resident macrophages and pericytes. Morphologically, perivascular resident macrophages undergo drastic changes from postnatal P7 to young adult (P30). In postnatal animals, most perivascular resident macrophages exhibit a spherical or nodular shape. In young adult mice, the majority of perivascular resident macrophages are elongated and display an orientation parallel to the vessels. In our imaging, some of the perivascular resident macrophages are caught in the act of transmigrating from the blood circulation. Pericytes also display morphological heterogeneity. In the P7 mice, pericytes are prominent on the capillary walls, relatively large and punctate, and less uniform. In contrast, pericytes in the P30 mice are relatively flat and uniform, and less densely distributed on the vascular network. With triple fluorescence labeling, we did not find obvious physical connection between the two systems, unlike neuronal-vascular coupling found in brain. However, using a fluorescent (FITC-conjugated dextran) tracer and the enzymatic tracer horseradish peroxidase (HRP), we observed robust neurovascular exchange, likely through transcytotic transport, evidenced by multiple vesicles present in the endothelial cells. Taken together, our data demonstrate the effectiveness of tissue-clearing methods as an aid in imaging the vascular architecture of the SL and SGNs in whole mounted mouse cochlear preparations. Structure is indicative of function. The finding of differences in vascular structure in postnatal and young adult mice may correspond with variation in hearing refinement after birth and indicate the status of functional activity. The decrease in capillary network density in the older animals may reflect the decreased energy demand from peripheral neural activity. The finding of active transcytotic transport from blood to neurons opens a potential therapeutic avenue for delivery of various growth factors and gene vectors into the inner ear to target SGNs.

Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive.

Neurovascular assessment in the critically ill patient.

AIM: To outline the pathophysiological processes involved in neurovascular impairment and compartment syndrome and examine common contributory factors within the development and clinical presentation of neurovascular impairment in critical care patients with musculoskeletal trauma. BACKGROUND: Thorough and systematic assessment of neurovascular status in critically ill patients with musculoskeletal trauma is crucial to detect secondary ischaemic injury and implement appropriate and timely treatment of any neurovascular deficits. METHOD: Current literature relating to neurovascular assessment and associated patient care was reviewed and utilised to outline distinct assessment components, indicators of neurovascular impairment and highlight the important issues for critical care nursing practice. RESULTS: Diminished limb perfusion secondary to vascular impairment and compartment syndrome are well documented. Complications associated with musculoskeletal trauma and surgical intervention can have wide-ranging effects on the patient's functional ability and overall outcome. It is crucial that appropriate neurovascular assessment is undertaken for patients admitted to the critical care unit following musculoskeletal trauma, crush injury, orthopaedic surgery (involving internal or external fixation of fractures) and those who may have experienced prolonged external pressure from casts or tight-fitting bandages. Several elements of neurovascular assessment are, however, more complex to undertake in the context of the unconscious or sedated critically ill patient. CONCLUSIONS: Effective practice requires that the critical care nurse has a comprehensive understanding of the aetiology, pathophysiology, physiological responses and clinical presentation associated with neurovascular impairment, secondary ischaemia and compartment syndrome. RELEVANCE TO CLINICAL PRACTICE: Undertaking an effective neurovascular assessment for patients at risk of neurovascular impairment or acute compartment syndrome (ACS) in the critical care setting can be problematic when patients are unable to communicate with the nurse. The risk of long-term functional impairment or limb loss can be significant in this group of patients, particularly following musculoskeletal trauma. This article reviews the aetiology and pathophysiology of neurovascular impairment in the critical care context and provides guidance for nurses undertaking this important element of nursing assessment with non-verbal, critically unwell patients. Informed practice in neurovascular assessment has the potential to enable early detection and timely management for these patients, which is crucial to optimise patient outcomes.

The effects of gender and test protocol on the results of head-up tilt test in patients with vasovagal syncope.

BACKGROUND: Head-up tilt testing (HUTT) is a well-established method for the diagnosis of reflex syncope. Some controversies exist whether gender and HUTT protocol influence HUTT results. AIM: To analyse the results of HUTT in patients with syncope in relation to their gender and used protocol of HUTT. METHODS: We retrospectively analysed data of 537 consecutive patients (313 women and 224 men), aged 13-79 years with history of neurally-mediated syncope referred to HUTT. The cardiogenic and neurological aetiology of syncope was excluded in all patients based on previous examination. In 375 patients standard HUTT (STD HUTT), according to the Westminster protocol, was used. In 257 patients in whom STD HUTT was negative, HUTT was continued with pharmacological provocation using isoproterenol intravenous infusion--114 patients (ISO HUTT) or sublingual nitroglycerin--143 patients (NTG HUTT). In the remaining 162 patients HUTT was performed according to the Italian protocol (ITL HUTT). The HUTT results were classified according to the VASIS scale. RESULTS: Female gender dominated, however, syncope was induced in a similar proportion of women and men (77.3 vs. 70.5%, NS). There were also no significant differences in the type of vasovagal response (VVR) to HUTT between women and men. Mixed type of VVR was the most frequent after isoproterenol provocation (ISO HUTT), whereas cardioinhibitory type of VVR was the most frequent after nitroglycerin provocation (NTG HUTT). CONCLUSIONS: There is no significant relationship between gender and the result of HUTT. The type of VVR is related to HUTT protocol--cardioinhibitory response is more frequent following nitroglycerin administration in comparison to standard protocol and HUTT with isoproterenol provocation.

The clinical spectrum of the neurological involvement in vasculitides.

Both the central nervous system (CNS) and the peripheral nervous system (PNS) are major target organs in primary vasculitides. They may either be affected in the setting of systemic vasculitis, potentially involving any other organ, or they may be the sole site of the inflammatory process. In both cases, the clinical pattern of PNS involvement is essentially uniform, presenting as sensory axonal polyneuropathy or mononeuritis multiplex. The damage is related to the ischemic occlusion of the vasanervorum due to small-vessel vasculitis. On the contrary, the range of manifestations of CNS vasculitis is much wider and several pathogenetic mechanisms are implicated, including angiitis of the hemispheres and spinal cord, thrombosis of dural sinuses, stenosis and aneurysms of medium and large arteries, granulomatous meningeal involvement and direct cytokine damage presenting with encephalopathy. Besides, even extracranial noninflammatory vascular disease may induce CNS symptoms, as is the case of carotid stenosis, vena cava syndrome and renovascular hypertension. In this paper we will review the broad spectrum of clinical manifestations of CNS and PNS neuropathy as they occur in primary systemic and non systemic vasculitides.

[Anatomy and physiology of the peripheral nerve]. / Organisation anatomique et physiologique du nerf périphérique.

The peripheral nerve provides the pathway for motor, sensory and vegetative axons belonging to the peripheral nervous system. It transmits information between these neurons and their peripheral effectors in both directions (sensory receptors, skeletal muscles and viscera). The afferences to the periphery correspond to the nerve motor content, whereas efferences from the periphery, in charge of delivering information to the central integrators, correspond to nerve-sensitive content. This information support depends on intrinsic properties of the nerve itself. Recent advances in cellular and molecular biology have provided a better understanding of nerve physiology, which are reviewed here as an indispensable basis to the study of its pathology.

[Pathology of Crow-Fukase syndrome].

Although the exact mechanisms underlying peripheral neuropathy in Crow-Fukase syndrome (CFS), also known as POEMS syndrome, remain obscure, careful scrutiny of the pathological changes in the peripheral nervous system (PNS) and systemic organs by using biopsy and autopsy materials may provide useful information regarding the pathogenesis and future therapeutics of the syndrome. In this review, previous biopsy/autopsy studies on CFS were systematically reviewed and the details of the pathological changes in the PNS and vascular system were noted. Most biopsied nerves revealed the characteristics of axonal degeneration and demyelination together; however, the nerve roots obtained at autopsy showed massive demyelination with few axonal changes. This morphological discrepancy can be interpreted as primary demyelination in the proximal PNS and secondary axonal degeneration in the distal PNS. Another histological hallmark of the syndrome is edema in the endoneurial space. Changes in the endoneurial and epineurial microvessels, including hyperplasia of endothelial cells, were occasionally observed. Endoneurial edema and microvascular changes can be attributed to the high serum concentration of vascular endothelial growth factor in this disorder, and the derangement in endoneurial homeostasis due to impaired blood-nerve barrier can be considered a possible pathomechanism underlying peripheral neuropathy in the CFS.

Neurovascular assessment.

The ability to carry out a neurovascular assessment on a patient's limb is an important skill for all registered nurses. All nurses, whether working in primary or acute care environments, are exposed to patients who have sustained injury or trauma to a limb or have a cast or restrictive bandages in place. The ability to detect a compromised limb through careful observation enables prompt referral and subsequent treatment, which may otherwise result in a permanent deficit. This article discusses the importance of undertaking neurovascular observations providing a step-by-step guide for the reader.

Foot temperature in diabetic polyneuropathy: innocent bystander or unrecognized accomplice?

AIM: To explore mechanisms by which temperature could influence the pathogenesis and symptoms of diabetic polyneuropathy. METHODS: We conducted a literature review attempting to identify mechanisms by which diabetic polyneuropathy could be affected by temperature. RESULTS: Cooling can theoretically hasten the progression of diabetic polyneuropathy through several different mechanisms. Specifically, cooling can enhance neuronal ischaemia, increase formation of reactive oxygen species, slow axonal transport, increase protein kinase C activity, and interfere with immune function. Short-term temperature fluctuations (both warming and cooling) can initiate and exacerbate neuropathic pain by causing neuronal hyperexcitability and functional deafferentation. Although normal fluctuations of distal extremity temperature may be sufficient for these effects, impaired thermoregulation may make the distal extremities more susceptible to temperature extremes. Eventually, a 'vicious cycle' may ensue, resulting in neuronal deterioration with further disruption of temperature regulation. Limited epidemiological data suggest a higher prevalence of diabetic polyneuropathy in populations living in colder locations, supporting our hypothesis. CONCLUSIONS: Variations in foot temperature may play an important but as yet unrecognized role in the development and symptoms of diabetic polyneuropathy. Further basic and clinical research exploring this concept could help elucidate the natural history of diabetic polyneuropathy and lead to novel therapeutic strategies.

A perfused rat brain model maintaining the connection between the central and peripheral nervous systems.

We have developed a new perfused brain model in rats. In this model, the cerebral circulation is separated from the systemic circulation, while the connections between the central and peripheral nervous systems are preserved. After bilateral common carotid, external carotid and vertebral artery ligation, bilateral common carotid arteries were cannulated to infuse rinsed human type O red blood cells mixed with modified Ringer's solution. To drain cerebral venous blood, external jugular veins were cannulated. Normal electrocortical activities were observed on electroencephalograms (EEGs) for more than 1h after the beginning of the perfusion. Somatosensory evoked potentials (SEPs) were also recorded. Direct infusion of pentylenetetrazol (PTZ) into the brain induced epileptic discharges on the EEGs and active dilation of cerebral arterioles, which was accompanied by an increase in systemic blood pressure (BP). The present model, in which we can change cerebral blood flow (CBF) and/or cerebral metabolism without directly affecting the systemic circulation, will provide a new approach to brain research.

[Adrenomedullin--the link between the sympathetic nervous system activation and peripheral vasodilatation in some patients with vasovagal syncope]. / Adrenomedullina-ogniwo laczace aktywacje ukladu wspólczulnego z obwodowa wazodylatacja u wybranych chorych z omdleniami wazowagalnymi.

UNLABELLED: Adrenomedullin (ADM) is a potent vasodilator playing role in regulation of central hemodynamic. The concentration of plasma ADM in healthy people increases under the influence of orthostatic stress. In patients with vasovagal syncope (VS) the changes in ADM concentration could be responsible either for syncope provocation or prevention. The aim of the study was to assess the influence of phase of the head-up tilt test (HUTT) in which the syncope occurred on the plasma concentration of ADM. MATERIAL AND METHODS: The study was performed in 25 patients (pts) (18 women and 7 men), mean age 45.0+/-16.1 years with cardiodepressive reactions during HUTT according to the Italian protocol with nitroglycerine (NTG) provocation if necessary: Syncope was caused in 23 pts due to vasovagal reaction: in 17 pts syncope occurred after NTG provocation (group 1), and in 6 pts occurred in the passive phase of tilt (group 2a), in 2 pts due to dysautonomic reactions (group 2b). The head-up tilt test was performed according to ESC guidelines. The blood for ADM concentration was drawn after 30 min supine rest (ADM 1) and immediately after syncope (ADM 2). ADM level was measured using radioimmunological method. The results. In group 1 plasma level of ADM significantly decreased after the HUTT (3.2+/-3.4 vs 1.7+/-1,4 pg/0.1 ml; p<0.05) and in group 2a increased significantly (1.3+/-0.8 vs 2.7+/-1.3 pg/0.1 ml; p<0.05) comparing to baseline values. The ADM concentration did not differ between the groups in baseline conditions and was significantly higher after the syncope in group 2a (p<0.05). Conclusions. The excessive increase of ADM concentration during the passive phase of HUTT could play the causative role in pathogenesis of VS occurring early during the HUTT. In patients with VS after NTG provocation the decrease of ADM concentration can be the result of hemodynamic changes in the presence of vasodilating drug and may be the mechanism that could prevent the syncope.

Autonomic arousal index: an automated detection based on peripheral arterial tonometry.

Arousals from sleep are associated with increased sympathetic activation and are therefore associated with peripheral vasoconstriction. We hypothesized that digital vasoconstrictions as measured by peripheral arterial tonometery (PAT), combined with an increase in pulse rate, would accurately reflect arousals from sleep, and can provide an autonomic arousal index (AAI). Based on a previously studied group of 40 sleep apnea patients simultaneously recorded by both polysomnography (PSG) and PAT systems, an automated algorithm using the PAT signal (and pulse rate derived from it) was developed for detection of arousals from sleep. This was further validated in a separate group of 96 subjects (85 patients referred with suspected obstructive sleep apnea and 11 healthy volunteers mean age 46.2+/-14.4 years, BMI 28.5+/-5.4 kg/m2). All underwent a whole night PSG with simultaneous PAT recording. The PSG recordings were blindly manually analyzed for arousals based on American Academy of Sleep Medicine (AASM) criteria, while PAT was scored automatically. There was a significant correlation between PSG and PAT arousals (R=0.82, p<0.0001) with a good agreement across a wide range of values, with a ROC curve having an area under the curve (AUC) of 0.88. We conclude that automated analysis of the peripheral arterial tonometry signal can detect EEG arousals from sleep, in a relatively quick and reproducible fashion.

How to avoid and manage nerve injuries associated with aortic surgery: ischemic neuropathy, traction injuries, and sexual derangements.

Both open and endovascular surgery of the infrarenal aorta are attended by risks of neurologic complications. Injury to the periaortic autonomic plexi frequently results in ejaculatory and erectile dysfunction. Traction injuries to lumbosacral nerve roots can cause peripheral nerve injury, most commonly exhibited as a femoral nerve deficit. The least common but most feared neurologic complication that can occur with infrarenal aortic surgery is ischemic injury to the spinal cord, or conus medullaris. The risk of this complication is increased with emergent or complicated aortic reconstructions. The importance of internal iliac artery perfusion to the development of ischemic cord and nerve root injury has been recognized. Although some neurologic complications may be avoidable by technical modifications, there is a small and probably irreducible neurologic risk to aortic surgery that should be considered when weighing options for treatment of aortic pathology.