Resting-state functional connectivity predicts motor cortex stimulation-dependent pain relief in fibromyalgia syndrome patients.

MRI-based resting-state functional connectivity (rsFC) has been shown to predict response to pharmacological and non-pharmacological treatments for chronic pain, but not yet for motor cortex transcranial magnetic stimulation (M1-rTMS). Twenty-seven fibromyalgia syndrome (FMS) patients participated in this double-blind, crossover, and sham-controlled study. Ten daily treatments of 10 Hz M1-rTMS were given over 2 weeks. Before treatment series, patients underwent resting-state fMRI and clinical pain evaluation. Significant pain reduction occurred following active, but not sham, M1-rTMS. The following rsFC patterns predicted reductions in clinical pain intensity after the active treatment: weaker rsFC of the default-mode network with the middle frontal gyrus (r = 0.76, p < 0.001), the executive control network with the rostro-medial prefrontal cortex (r = 0.80, p < 0.001), the thalamus with the middle frontal gyrus (r = 0.82, p < 0.001), and the pregenual anterior cingulate cortex with the inferior parietal lobule (r = 0.79, p < 0.001); and stronger rsFC of the anterior insula with the angular gyrus (r = - 0.81, p < 0.001). The above regions process the attentional and emotional aspects of pain intensity; serve as components of the resting-state networks; are modulated by rTMS; and are altered in FMS. Therefore, we suggest that in FMS, the weaker pre-existing interplay between pain-related brain regions and networks, the larger the pain relief resulting from M1-rTMS.

Classification of painful or painless diabetic peripheral neuropathy and identification of the most powerful predictors using machine learning models in large cross-sectional cohorts.

BACKGROUND: To improve the treatment of painful Diabetic Peripheral Neuropathy (DPN) and associated co-morbidities, a better understanding of the pathophysiology and risk factors for painful DPN is required. Using harmonised cohorts (N = 1230) we have built models that classify painful versus painless DPN using quality of life (EQ5D), lifestyle (smoking, alcohol consumption), demographics (age, gender), personality and psychology traits (anxiety, depression, personality traits), biochemical (HbA1c) and clinical variables (BMI, hospital stay and trauma at young age) as predictors. METHODS: The Random Forest, Adaptive Regression Splines and Naive Bayes machine learning models were trained for classifying painful/painless DPN. Their performance was estimated using cross-validation in large cross-sectional cohorts (N = 935) and externally validated in a large population-based cohort (N = 295). Variables were ranked for importance using model specific metrics and marginal effects of predictors were aggregated and assessed at the global level. Model selection was carried out using the Mathews Correlation Coefficient (MCC) and model performance was quantified in the validation set using MCC, the area under the precision/recall curve (AUPRC) and accuracy. RESULTS: Random Forest (MCC = 0.28, AUPRC = 0.76) and Adaptive Regression Splines (MCC = 0.29, AUPRC = 0.77) were the best performing models and showed the smallest reduction in performance between the training and validation dataset. EQ5D index, the 10-item personality dimensions, HbA1c, Depression and Anxiety t-scores, age and Body Mass Index were consistently amongst the most powerful predictors in classifying painful vs painless DPN. CONCLUSIONS: Machine learning models trained on large cross-sectional cohorts were able to accurately classify painful or painless DPN on an independent population-based dataset. Painful DPN is associated with more depression, anxiety and certain personality traits. It is also associated with poorer self-reported quality of life, younger age, poor glucose control and high Body Mass Index (BMI). The models showed good performance in realistic conditions in the presence of missing values and noisy datasets. These models can be used either in the clinical context to assist patient stratification based on the risk of painful DPN or return broad risk categories based on user input. Model's performance and calibration suggest that in both cases they could potentially improve diagnosis and outcomes by changing modifiable factors like BMI and HbA1c control and institute earlier preventive or supportive measures like psychological interventions.

Clinical Effects of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex Are Associated With Changes in Resting-State Functional Connectivity in Patients With Fibromyalgia Syndrome.

In this double-blinded, sham-controlled, counterbalanced, and crossover study, we investigated the potential neuroplasticity underlying pain relief and daily function improvements following repetitive transcranial magnetic stimulation of the motor cortex (M1-rTMS) in fibromyalgia syndrome (FMS) patients. Specifically, we used magnetic resonance imaging (MRI) to examine changes in brain structural and resting-state functional connectivity (rsFC) that correlated with improvements in FMS symptomology following M1-rTMS. Twenty-seven women with FMS underwent real and sham treatment series, each consisting of 10 daily treatments of 10Hz M1-rTMS over 2 weeks, with a washout period in between. Before and after each series, participants underwent anatomical and resting-state functional MRI scans and questionnaire assessments of FMS-related clinical pain and functional and psychological burdens. The expected reductions in FMS-related symptomology following M1-rTMS occurred with the real treatment only and correlated with rsFC changes in brain areas associated with pain processing and modulation. Specifically, between the ventromedial prefrontal cortex and the M1 (t = -5.54, corrected P = .002), the amygdala and the posterior insula (t = 5.81, corrected P = .044), and the anterior and posterior insula (t = 6.01, corrected P = .029). Neither treatment significantly changed brain structure. Therefore, we provide the first evidence of an association between the acute clinical effects of M1-rTMS in FMS and functional alterations of brain areas that have a significant role in the experience of chronic pain. Structural changes could potentially occur over a more extended treatment period. PERSPECTIVE: We show that the neurophysiological mechanism of the improvement in fibromyalgia symptoms following active, but not sham, rTMS applied to M1 involves changes in resting-state functional connectivity in sensory, affective and cognitive pain processing brain areas, thus substantiating the essence of fibromyalgia syndrome as a treatable brain-based disorder.

[SMALL FIBER POLYNEUROPATHY IN YOUNG PATIENTS].

INTRODUCTION: Small fiber polyneuropathy (SFPN) is associated with a variety of clinical conditions. Common to these conditions is the deviation from healthy physiological homeostatic balance, which hinders small fiber neurons viability, resulting in their damage. The most common cause for SFPN in the western world is diabetes, followed by a long list of other risk-factors, some are age-related. Accumulating evidence suggests that in young patients a leading cause (up-to 50% of cases) is autoimmune-related. A variety of symptoms can be seen in SFPN. Commonly, first to appear are sensory symptoms in the extremities. Autonomic symptoms can then join, or even be the presenting symptoms. This sensory-autonomic combination can have a dramatic mal-effect on the patient's quality of life. Diagnosis is based primarily on skin biopsy and/or Autonomic-Functional-Testing. Often, in cases where no etiology is identified, EMG is normal and the skin biopsy/autonomic testing is not performed, clinicians tend to incorrectly diagnose a non-organic situation. Correct and preferably early diagnosis is of essence since peripheral fibers can recover if the disease pathophysiological factor is removed, leading to less suffering and improved quality of life of patients.

DOLORisk: study protocol for a multi-centre observational study to understand the risk factors and determinants of neuropathic pain.

Background: Neuropathic pain is an increasingly prevalent condition and has a major impact on health and quality of life. However, the risk factors for the development and maintenance of neuropathic pain are poorly understood. Clinical, genetic and psychosocial factors all contribute to chronic pain, but their interactions have not been studied in large cohorts. The DOLORisk study aims to study these factors. Protocol: Multicentre cross-sectional and longitudinal cohorts covering the main causes leading to neuropathic pain (e.g. diabetes, surgery, chemotherapy, traumatic injury), as well as rare conditions, follow a common protocol for phenotyping of the participants. This core protocol correlates answers given by the participants on a set of questionnaires with the results of their genetic analyses. A smaller number of participants undergo deeper phenotyping procedures, including neurological examination, nerve conduction studies, threshold tracking, quantitative sensory testing, conditioned pain modulation and electroencephalography. Ethics and dissemination: All studies have been approved by their regional ethics committees as required by national law. Results are disseminated through the DOLORisk website, scientific meetings, open-access publications, and in partnership with patient organisations. Strengths and limitations: Large cohorts covering many possible triggers for neuropathic painMulti-disciplinary approach to study the interaction of clinical, psychosocial and genetic risk factorsHigh comparability of the data across centres thanks to harmonised protocolsOne limitation is that the length of the questionnaires might reduce the response rate and quality of responses of participants.

Neuropathic pain.

Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aß, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.

Clinical and genetic findings in eight Israeli patients with transthyretin-associated familial amyloid polyneuropathy.

BACKGROUND: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid. OBJECTIVES: To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel. METHODS: We evaluated eight patients clinically and genetically during the years 2006 to 2011. RESULTS: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotoraxonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation. CONCLUSIONS: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.

Tonic pain and continuous EEG: prediction of subjective pain perception by alpha-1 power during stimulation and at rest.

OBJECTIVE: Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. METHODS: Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. RESULTS: NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). CONCLUSIONS: Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. SIGNIFICANCE: The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation.

Pronociceptive pain modulation in patients with painful chemotherapy-induced polyneuropathy.

CONTEXT: Several chemotherapy agents induce polyneuropathy that is painful for some patients, but not for others. We assumed that these differences might be attributable to varying patterns of pain modulation. OBJECTIVES: The aim of the present study was to evaluate pain modulation in such patients. METHODS: Twenty-seven patients with chemotherapy-induced polyneuropathy were tested for detection thresholds (cold, warm, and mechanical) in both the forearm and foot, as well as for heat pain threshold, mechanical temporal summation (TS), and conditioned pain modulation (CPM; also known as the diffuse noxious inhibitory control-like effect), which were tested in the upper limbs. RESULTS: Positive correlations were found between clinical pain levels and both TS (r=0.52, P=0.005) and CPM (r=0.40, P=0.050) for all patients. In addition, higher TS was associated with less efficient CPM (r=0.56, P=0.004). The group of patients with painful polyneuropathy (n=12) showed a significantly higher warm detection threshold in the foot (P=0.03), higher TS (P<0.01), and less efficient CPM (P=0.03) in comparison to the group with nonpainful polyneuropathy. CONCLUSION: The painfulness of polyneuropathy is associated with a "pronociceptive" modulation pattern, which may be primary to the development of pain. The higher warm sensory thresholds in the painful polyneuropathy group suggest that the severity of polyneuropathy may be another factor in determining its painfulness.

Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states.

PURPOSE OF REVIEW: There is a growing body of knowledge on pain modulation in various disease states. This article reviews the state of the art regarding the clinical relevance of pain inhibition as revealed by 'pain inhibits pain' test paradigms, trying to organize the clinically relevant data, and emphasizing the pathophysiology of pain. In line with recent experts' recommendations, the term conditioned pain modulation (CPM) will be used, replacing the previous terms 'diffuse noxious inhibitory control (DNIC)' or 'DNIC-like' effects. RECENT FINDINGS: Most of the work in this context was done on the idiopathic pain syndromes, such as irritable bowel syndrome, temporomandibular disorders, fibromyalgia, and tension type headache. The pattern of reduced CPM efficiency seems common to these syndromes and an assertion is made that low CPM efficiency, reflecting low pain inhibitory capacity, is a pathogenetic factor in the development of the idiopathic pain syndromes. Low CPM efficiency was shown to be predictive of acute and chronic postoperative pain, and, in some reports, to be associated with neuropathic pain levels. SUMMARY: Low CPM efficiency is associated with higher pain morbidity and vice versa. Further work is awaited on clarifying plasticity of CPM and its relevance to selection and efficacy of pain therapy.

An experimental paradigm for the prediction of Post-Operative Pain (PPOP).

Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative short-term and long-term effects on the mother. Prior to women undergoing surgery, can we predict who is at risk for developing significant postoperative pain and potentially prevent or minimize its negative consequences? These are the fundamental questions that a team from the University of Washington, Stanford University, the Catholic University in Brussels, Belgium, Santa Joana Women's Hospital in São Paulo, Brazil, and Rambam Medical Center in Israel is currently evaluating in an international research collaboration. The ultimate goal of this project is to provide optimal pain relief during and after cesarean section by offering individualized anesthetic care to women who appear to be more 'susceptible' to pain after surgery. A significant number of women experience moderate or severe acute post-partum pain after vaginal and cesarean deliveries. (1) Furthermore, 10-15% of women suffer chronic persistent pain after cesarean section. (2) With constant increase in cesarean rates in the US (3) and the already high rate in Brazil, this is bound to create a significant public health problem. When questioning women's fears and expectations from cesarean section, pain during and after it is their greatest concern. (4) Individual variability in severity of pain after vaginal or operative delivery is influenced by multiple factors including sensitivity to pain, psychological factors, age, and genetics. The unique birth experience leads to unpredictable requirements for analgesics, from 'none at all' to 'very high' doses of pain medication. Pain after cesarean section is an excellent model to study post-operative pain because it is performed on otherwise young and healthy women. Therefore, it is recommended to attenuate the pain during the acute phase because this may lead to chronic pain disorders. The impact of developing persistent pain is immense, since it may impair not only the ability of women to care for their child in the immediate postpartum period, but also their own well being for a long period of time. In a series of projects, an international research network is currently investigating the effect of pregnancy on pain modulation and ways to predict who will suffer acute severe pain and potentially chronic pain, by using simple pain tests and questionnaires in combination with genetic analysis. A relatively recent approach to investigate pain modulation is via the psychophysical measure of Diffuse Noxious Inhibitory Control (DNIC). This pain-modulating process is the neurophysiological basis for the well-known phenomenon of 'pain inhibits pain' from remote areas of the body. The DNIC paradigm has evolved recently into a clinical tool and simple test and has been shown to be a predictor of post-operative pain.(5) Since pregnancy is associated with decreased pain sensitivity and/or enhanced processes of pain modulation, using tests that investigate pain modulation should provide a better understanding of the pathways involved with pregnancy-induced analgesia and may help predict pain outcomes during labor and delivery. For those women delivering by cesarean section, a DNIC test performed prior to surgery along with psychosocial questionnaires and genetic tests should enable one to identify women prone to suffer severe post-cesarean pain and persistent pain. These clinical tests should allow anesthesiologists to offer not only personalized medicine to women with the promise to improve well-being and satisfaction, but also a reduction in the overall cost of perioperative and long term care due to pain and suffering. On a larger scale, these tests that explore pain modulation may become bedside screening tests to predict the development of pain disorders following surgery.

Cardiovascular risk factors in restless legs syndrome.

We conducted a population-based cross-sectional study to assess prevalence of cardiovascular risk factors in subjects with and without restless legs syndrome (RLS). Adults attending their annual checkup completed the International RLS Study Group questionnaire and underwent an interview by a neurologist. Data from the annual checkup were compared between subjects with and without RLS. The prevalence of RLS was 6.7% (95% CI 5.45-7.95) among 1,537 responders. RLS subjects' blood tests showed significantly higher fasting blood glucose level (P = 0.029), higher prevalence of hypercholesterolemia (P = 0.029) and reduced renal function (P = 0.013), and increased prevalence of low hematocrit (P = 0.008). RLS subjects weighed more (P = 0.029), had a higher BMI (P = 0.033), larger hip circumference (P = 0.033), and were less fit (P = 0.010). To control for interactions among statistical predictors, we also employed multivariate logistic regression models adjusted for age, gender, smoking, BMI, hemoglobin, glucose, HDL/LDL cholesterol, triglycerides, and creatinine. We found that female gender (OR 2.16; 95% CI 1.11-4.17), smoking (OR 1.82; 95% CI, 1.10-3.00), and HDL/LDL cholesterol (OR 0.18; 95% CI 0.034-0.90) were significantly associated with RLS compared with subjects without RLS. RLS was associated with cardiovascular risk factors.

Enhanced presurgical pain temporal summation response predicts post-thoracotomy pain intensity during the acute postoperative phase.

UNLABELLED: Recent evidence points to an association between experimental pain measures obtained preoperatively and acute postoperative pain (POP). We hypothesized that pain temporal summation (TS) might be an additional predictor for POP insofar as it represents the neuroplastic changes that occur in the central nervous system following surgery. Therefore, a wide range of psychophysical tests (TS to heat and mechanical repetitive stimuli, pain threshold, and suprathreshold pain estimation) and personality tests (pain catastrophizing and anxiety levels) were administered prior to thoracotomy in 84 patients. POP ratings were evaluated on the 2nd and 5th days after surgery at rest (spontaneous pain) and in response to activity (provoked pain). Linear regression models revealed that among all assessed variables, enhanced TS and higher pain scores for mechanical stimulation were significantly associated with greater provoked POP intensity (overall r2 = 0.225, P = .008). Patients who did not demonstrate TS to both modalities reported lower scores of provoked POP as compared with patients who demonstrated TS in response to at least 1 modality (F = 4.59 P = .013). Despite the moderate association between pain catastrophizing and rest POP, none of the variables predicted the spontaneous POP intensity. These findings suggest that individual susceptibility toward a greater summation response may characterize patients who are potentially vulnerable to augmented POP. PERSPECTIVE: This study proposed the role of pain temporal summation assessed preoperatively as a significant psychophysical predictor for acute postoperative pain intensity. The individual profile of enhanced pain summation is associated with the greater likelihood of higher postoperative pain scores.

An animal model of chemotherapy-induced vagal neuropathy.

In this study we establish an animal model of chemotherapy-induced autonomic neuropathy. Rats were injected with vincristine (30 and 100 microg/kg/day) for 2 weeks while cardiovascular parameters were collected telemetrically. Vincristine caused a dose-dependent decrease in vagal activity expressed by decreased parasympathetic parameters of heart rate variability, without expression of damage to the cardiac sympathetic innervation. This model can serve in assessing the potential contribution of chemotherapy-induced vagal neuropathy to morbidity and mortality.

Microemboli in MCA ipsilateral to occluded common carotid artery: an observation and short review of the literature.

Sixty-five years old patient suffering from acute stroke was treated by rTPA intravenously. TCD monitoring of both middle cerebral arteries (MCA) was carried out simultaneously with administration of rTPA. Seven microemboli were found in right and four in left MCA. Duplex ultrasound, CT angiography and digital subtractional angiography revealed occlusion of left common carotid artery (CCA) and moderate to severe stenosis of right internal carotid artery (ICA). The case presented here is, to the best of our knowledge, the first description of MCA microemboli signals in patient with occlusion of ipsilateral CCA. This location of occlusion eliminates the possibility of microemboli passage from carotid bulb proximally to the site of occlusion through the ipsilateral external carotid artery or from the distal stump of occluded ICA. The possibility of emboli from contralateral stenosed ICA through the patent anterior communicating artery (ACoA) or from the distal stump of occluded CCA seems to be the most probable explanation.

Preoperative cerebral hemodynamics and shunting during carotid endarterectomy in patients with severe unilateral carotid stenosis.

PURPOSE: To estimate the possible predictors for the need for shunting during carotid endarterectomy in patients with severe unilateral carotid stenosis based on preoperative transcranial Doppler sonographic examination. MATERIALS AND METHODS: One hundred twenty-six patients were included in the study. Pulsatility index, flow acceleration, peak systolic velocity, and mean velocity were measured in the middle cerebral artery (MCA) and anterior cerebral artery on both sides. Cerebrovascular reactivity (CVR) was evaluated in 21 patients with shunts and in 55 patients without shunts. RESULTS: The shunted and nonshunted groups did not differ with regard to demographic and clinical characteristics. The side-to-side difference in peak systolic velocity and mean velocity of the MCA was significantly higher in patients with shunts. CVR were significantly higher in the patients without shunts (36.0 +/- 17.2%) than in patients with shunts (16.6 +/- 11.4%; p = 0.0003). The peak systolic velocity and mean velocity asymmetry of the MCA had relatively low receiver operating characteristics, whereas CVR exhibited a relatively high accuracy in predicting the need for shunting. CONCLUSION: Low CVR and increased asymmetry of MCA velocities were found in patients who subsequently required shunting during carotid endarterectomy. The relatively low accuracy of the MCA asymmetry should prevent the use of this criterion as a reliable preoperative predictor for shunting during carotid surgery, whereas CVR was more accurate and may prove useful in this setting.

Duplex ultrasound verified by angiography in patients with severe primary and restenosis of internal carotid artery.

There are very limited data in the literature about the reliability of duplex ultrasound (DU) verified by angiography in patients with restenosis of the internal carotid artery (ICA) after carotid surgery compared with primary carotid artery stenosis patients. Our objective was to compare the reliability of DU verified by conventional angiography in the diagnosis of severe primary stenosis versus restenosis of ICA. One hundred thirty-four patients (238 arteries) were examined by both DU and angiography. Severe stenosis (>70%) was found in 47 primary stenotic arteries and in 70 restenotic arteries. Accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value were obtained for basic DU criteria after verification of ultrasound data by angiography. The best accuracy for detection of >70% stenosis by end diastolic velocity was found for the velocity of 70 cm/sec or more in both groups, but accuracy for the restenosis group was significantly higher (96.9% vs. 89.8%, p = 0.025). Additionally, specificity (p = 0.01) and PPV (p = 0.01) were significantly higher in the restenosis group. The best accuracy for detection of >70% stenosis by peak systolic velocity was found for the velocity of 220 cm/sec or more for restenoses and 200 cm/sec or more for primary stenoses. The accuracy of the ultrasound was significantly higher in the restenosis group (94.6% vs. 87%, p = 0.04), as were specificity (p = 0.01) and PPV (p = 0.02). The diagnosis of severe restenosis by DU is reliable and can be used for decision making regarding surgery or stenting without angiography. In patients with Doppler parameters pointing to borderline moderate/severe primary carotid stenosis and technically complicated cases, angiography in addition to sonography before surgery is recommended.

Does hysterectomy affect genital sensation?

OBJECTIVES: To evaluate vaginal and clitoral sensation before and after hysterectomy and to assess pre- and post-surgery changes in sexual function. STUDY DESIGN: Quantitative sensory thresholds for warm, cold, and vibratory sensations were measured at the vagina and clitoris 1 day prior to and 3 months following surgery. A survey was performed 18 months following operation to evaluate long-term changes in sexual function. PARTICIPANTS: Twenty-seven women, aged 30-57 years, who were admitted for elective hysterectomy. MAIN OUTCOME MEASURES: Genital sensation and reported sexual function. RESULTS: There was significant deterioration in sensation to cold and warm stimuli at the anterior and posterior vaginal wall after surgery. Vaginal vibratory sensation thresholds tended to increase. Clitoral thermal and vibratory sensation thresholds remained unchanged before and after surgery. Of the 22 patients who participated in the follow-up survey, 17 did not report any decline in sexual function, while 4 patients reported deterioration in genital sensation and in sexual function. CONCLUSION: The results demonstrate quantifiable sensory loss in the vagina after hysterectomy, with preservation of clitoral sensation. Only a minority of patients reported a decline in their sexual function. These findings highlight the relative importance of clitoral as compared to vaginal sensation in sexual function.

Increased BBB permeability by parasympathetic sphenopalatine ganglion stimulation in dogs.

The blood-brain barrier (BBB) is a major obstacle for movement of large molecules to and from the brain. Stimulation of the sphenopalatine ganglion (SPG), the major source of parasympathetic innervation to brain vasculature, is known to vasodilate brain vessels, and has recently been shown to also increase the permeability of the BBB in the rat. In this work, we studied the effect of SPG stimulation on BBB permeability in larger animals--Beagle dogs. Left SPG was exposed by lateral approach in five Beagle dogs, and stimulated at 10 Hz. FITC labeled 10 kDa dextran was continuously infused to the left atrium during stimulation, and cerebral angiography was periodically obtained via the vertebral artery. Three control dogs received labeled dextran, without SPG exposure or stimulation. Brains were perfused with saline thoroughly at the end of stimulation, and samples from various regions were taken for fluorescence reading of tissue homogenates. Cerebral vasodilatation was evidenced in all but one dog, whose fluorescence results were consequently excluded from analysis, assuming that its SPG had been damaged by surgery. Fluorescence was significantly higher in the four stimulated compared to the three non-stimulated animals; e.g. mean FITC-dextran concentration in the anterior brain regions was 0.98+/-0.12 ug (mean+/-S.D.) FITC/g brain for experimental animals, and 0.40+/-0.02 for controls (p<0.01). No effect was seen in the pons and cerebellum (0.68+/-0.22 vs. 0.60+/-0.03, NS) whose vascular innervation is supplied by the otic rather than the SPG ganglion. SPG stimulation appears to be an effective way to increase BBB permeability, allowing introduction of large molecules to the brain. This could be a therapeutic method for a wide variety of brain disorders, including tumors and neurodegenerative diseases.