Understanding the role of cerebellum in early Parkinson's disease: a structural and functional MRI study.

Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson's disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol. The following MRI analyses were performed: (1) volumes of 5 cerebellar regions of interest (sensorimotor and cognitive cerebellum, dentate, interposed, and fastigial nuclei); (2) microstructural integrity of the cerebellar white matter connections (inferior, middle, and superior cerebellar peduncles); (3) functional connectivity at rest of the 5 regions of interest already described in point 1 with the rest of brain. Compared to controls, early PD patients showed a significant decrease in gray matter volume of the dentate, interposed and fastigial nuclei, bilaterally. They also showed abnormal, bilateral white matter microstructural integrity in all 3 cerebellar peduncles. Functional connectivity of the 5 cerebellar regions of interest with several areas in the midbrain, basal ganglia and cerebral cortex was altered. Finally, there was a positive correlation between abnormal functional connectivity of the fastigial nucleus with the volume of the nucleus itself and a negative correlation with axial symptoms severity. Our results showed that structural and functional alterations of the cerebellum are present in PD patients and these changes contribute to the pathophysiology of PD in the early phase.

High intraoperative blood product requirements in liver transplantation: risk factors and impact on the outcome.

OBJECTIVE: Liver transplantation (LT) is associated with a significant bleeding and the high transfusion requirements (HTR) negatively affect the outcome of LT patients. Our primary aim was to identify potential predictors of intraoperative transfusion requirements. Secondarily, we investigated, the effect of transfusion requirements on different clinical outcomes, including short-term morbidity and mortality. PATIENTS AND METHODS: Data collected in 219 adult LT from a deceased donor, grouped according to HTR (defined as the need of 5 or more red blood cell units), were compared. RESULTS: We found that previous portal vein thromboses (p=0.0156), hemoglobin (Hb) (p<0.0001), International Normalized Ratio (INR) (p=0.0010) at transplant and veno-venous by-pass (p=0.0048) independently predicted HTR. HTR was always associated with poorer outcomes, including higher simplified acute physiology II score at Intensive Care Unit admission (p=0.0005), higher rates of pulmonary infections (p=0.0015) and early rejection (p=0.0176), longer requirement of mechanical ventilation, (p<0.0001), more frequent need for hemodialysis after transplantation (p=0.0036), overall survival (p=0.0010) and rate of day-90 survival (p=0.0016). CONCLUSIONS: This study identified specific risk factors for HTR and confirmed the negative impact exerted by HTR on clinical outcomes, including recipient survival. Prospective investigations are worth to assess whether correcting pre-transplant Hb and INR levels may effectively reduce blood product need and improve prognosis.

Strength of interference screw fixation of meniscus prosthesis matches native meniscus attachments.

PURPOSE: Meniscal surgery is one of the most common orthopaedic surgical interventions. Total meniscus replacements have been proposed as a solution for patients with irreparable meniscal injuries. Reliable fixation is crucial for the success and functionality of such implants. The aim of this study was to characterise an interference screw fixation system developed for a novel fibre-matrix-reinforced synthetic total meniscus replacement in an ovine cadaveric model. METHODS: Textile straps were tested in tension to failure (n = 15) and in cyclic tension (70-220 N) for 1000 cycles (n = 5). The textile strap-interference screw fixation system was tested in 4.5 mm-diameter single anterior and double posterior tunnels in North of England Mule ovine tibias aged > 2 years using titanium alloy (Ti6Al4Va) and polyether-ether-ketone (PEEK) screws (n ≥ 5). Straps were preconditioned, dynamically loaded for 1000 cycles in tension (70-220 N), the fixation slippage under cyclic loading was measured, and then pulled to failure. RESULTS: Strap stiffness was at least 12 times that recorded for human meniscal roots. Strap creep strain at the maximum load (220 N) was 0.005 following 1000 cycles. For all tunnels, pull-out failure resulted from textile strap slippage or bone fracture rather than strap rupture, which demonstrated that the textile strap was comparatively stronger than the interference screw fixation system. Pull-out load (anterior 544 ± 119 N; posterior 889 ± 157 N) was comparable to human meniscal root strength. Fixation slippage was within the acceptable range for anterior cruciate ligament graft reconstruction (anterior 1.9 ± 0.7 mm; posterior 1.9 ± 0.5 mm). CONCLUSION: These findings show that the textile attachment-interference screw fixation system provides reliable fixation for a novel ovine meniscus implant, supporting progression to in vivo testing. This research provides a baseline for future development of novel human meniscus replacements, in relation to attachment design and fixation methods. The data suggest that surgical techniques familiar from ligament reconstruction may be used for the fixation of clinical meniscal prostheses.

Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC).Design: multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular = 125, traumatic = 83, anoxic = 56, others = 14).Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity.Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO.Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Impact of a carotid stenosis on cardiac surgery: marker more than risk factor.

A concurrent carotid and cardiac disease is the paradigmatic expression of a multidistrictal vasculopathy related to an atherosclerotic burden, that shares the same risk factors and onset pathophysiological mechanisms. The absolute incidence of a stroke after open heart surgery (OHS) is about 2%, higher in case of combined cardiac procedures, with a negative prognostic impact in terms of in-hospital mortality and neurological morbidity. Heterogenous and interlinked risk factors contribute to the genesis of cerebral injuries after OHS outlining patient general features, vascular risk parameters and severity indeces of cardiac disease; a model stroke for patients undergoing cardiac surgery may be helpful so as to identify subsets of patients at high risk and select the most appropriate strategy. A critical carotid stenosis should be contextualized not as the Romadirect cause of stroke, but as a risk marker of high grade atherosclerotic systemic disease, predicting a potential severe aortic or intracerebral vessel disease and leading to recognize and study carefully these multivascular patients before operation. The idea of carotid plaque as active embolic source is valid only in case of vulnerable plaques in relation to the potential detachment of particulate material. Until now the neurological status, in accordance with symptomatic or asymptomatic carotid stenosis, has markedly influenced the operation timing and the choice of the surgical strategy. Except for special circumstances, we generally suggest a 'reverse staged' surgical strategy with cardiac surgery before carotid timing in elective patients recommending strongly a pharmacological neuroprotection relied on the administration of Sodium Thiopentone. Most of carotid stenosis in patients undergoing OHS is asymptomatic and doesn't represent a proven independent risk factor for postoperative stroke; indeed, we advocate that synchronous surgical treatment of both carotid and cardiac lesions is burdened from higher perioperative mortality and stroke rates rightfully unjustifiable according to potential benefits.

Topical Treatments for Localized Neuropathic Pain.

PURPOSE OF REVIEW: Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially promising effect on pain reduction. In this narrative review, we describe the available compounds for topical use in LNP syndromes and address their potential efficacy according to the literature. RECENT FINDINGS: Local anaesthetics (e.g., lidocaine, bupivacaine and mepivacaine), as well as general anaesthetic agents (e.g., ketamine), muscle relaxants (e.g., baclofen), capsaicin, anti-inflammatory drugs (e.g., diclofenac), salicylates, antidepressants (e.g., amitriptyline and doxepin), α2 adrenergic agents (e.g., clonidine), or even a combination of them have been tested in various applications for the treatment of LNP. Few of them have reached a sufficient level of evidence to support systematic use as treatment options. Relatively few systemic side effects or drug-drug interactions and satisfactory efficacy seem to be the benefits of topical treatments. More well-organized and tailored studies are necessary for the further conceptualization of topical treatments for LNP.

Temporal summation of the nociceptive withdrawal reflex involves deactivation of posterior cingulate cortex.

BACKGROUND: Temporal summation of pain sensation is pivotal both in physiological and pathological nociception. In humans, it develops in parallel with temporal summation of the nociceptive withdrawal reflex (NWR) of the lower limb, an objective representation of the temporal processing of nociceptive signals into the spinal cord. METHODS: To study the contribution of cortical and subcortical structures in temporal summation of pain reflex responses, we compared the fMRI signal changes related to the temporal summation threshold (TST) of the NWR with that related to the single NWR response. We studied 17 healthy subjects using a stimulation paradigm previously determined to evoke both the TST of the NWR (SUMM) and the NWR single response (SING). RESULTS: We found a significant activation in left (contralateral) primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII), bilateral insula, anterior cingulate cortex (ACC) and bilateral thalamus during both SUMM and SING conditions. The SUMM versus SING contrast revealed a significant deactivation in the posterior cingulate cortex (PCC) and bilateral middle occipital gyrus in SUMM when compared to SING condition. CONCLUSIONS: Our data support the hypothesis that temporal summation of nociceptive reflex responses is driven through a switch between activation and deactivation of a specific set of brain areas linked to the default mode network. This behaviour could be explained in view of the relevance of the pain processing induced by temporal summation, recognized as a more significant potential damaging condition with respect to a single, isolated, painful stimulation of comparable pain intensity. SIGNIFICANCE: The study demonstrated that TST of the NWR involves a selective deactivation of PCC.

Italian standardization of the Apples Cancellation Test.

Hemispatial neglect due to right parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, resulting in poor functional gain. Recent research has shown that different types of neglect can impact in a different way on rehabilitation outcomes. The availability of a sensitive test, useful for distinguishing egocentric and allocentric forms of neglect, may be clinically important as all current clinical instruments fail to distinguish between these forms of disturbance, yet they differentially predict outcome. The Apples Test is a new instrument useful to evaluate both egocentric and allocentric forms of neglect. In order to establish Italian norms for this diagnostic instrument the test was administered to a sample of 412 healthy people of both genders (201 M and 211 F), aged from 20 to 80 years enrolled from 14 different rehabilitation centers in Italy. Based on the data, we established pathological performance cut-offs for the accuracy score (total omission errors), the asymmetry score for egocentric neglect (omission error difference), the asymmetry score for allocentric neglect (commission error difference) and execution time. The usefulness of the Apples Test for diagnostic purposes is illustrated by presenting three patients with different forms of neglect (egocentric, allocentric and mixed neglect).

Botulinum toxin type A potentiates the effect of neuromotor rehabilitation of Pisa syndrome in Parkinson disease: a placebo controlled study.

INTRODUCTION: Pisa syndrome (PS) is a tonic lateral flexion of trunk that represents a disabling complication of advanced Parkinson disease (PD). Conventional rehabilitation treatment (CT) ameliorates axial posture and trunk mobility in PD patients, but the improvement tends to wane in 4-6 months. Botulin toxin (BT) may reduce muscle hyperactivity, therefore improving CT effectiveness. We evaluated whether the injection of incabotulinum toxin type A (iBTA) into the hyperactive trunk muscles might improve the effectiveness of rehabilitation in a group of PD patients with PS. METHODS: Twenty-six PD patients were enrolled in a randomized placebo-controlled trial. Group A was treated with iBTA before undergoing CT (a 4-week intensive programme), while Group B received saline before the 4-week CT treatment. Patients were evaluated at baseline, at the end of the rehabilitative period, 3 and 6 months with kinematic analysis of movement, UPDRS, Functional Independence Measure and Visual Analog Scale for pain. RESULTS: At the end of the rehabilitation period, both groups improved significantly in terms of static postural alignment and of range of motion. Group A showed a significantly more marked reduction in pain score as compared with Group B and a more prolonged efficacy on several clinical and kinematic variables. CONCLUSIONS: Our preliminary data suggest that BT may be considered an important addition to the rehabilitation programme for PD subjects with PS for improving axial posture and trunk mobility, as well as for a better control of pain.

Chronic migraine in women is associated with insulin resistance: a cross-sectional study.

BACKGROUND AND PURPOSE: Migraine is a common neurological disorder. It can be divided into episodic migraine (EM) and chronic migraine (CM), based on headache frequency. Some studies have shown that insulin sensitivity is impaired in migraine; moreover, hypertension, diabetes and obesity are common in patients with CM. The aim of this study was to assess serum glucose, insulin levels and insulin resistance (IR) in a sample of episodic migraineurs, chronic migraineurs and non-pain healthy controls. METHODS: Eighty-three women with EM, 83 with CM and 83 healthy controls were recruited. Headache was diagnosed according to the latest International Classification of Headache Disorders 2 criteria. Waist circumference, body mass index (BMI) and blood pressure were measured. Checked metabolic parameters included fasting glucose, the 2 h 75 g oral glucose tolerance test (2 h OGTT), serum HbA1c, blood lipid profile, C-reactive protein and prolactin. The homeostasis model assessment formula was used to calculate IR. RESULTS: A significant prevalence of IR in CM was observed (P = 0.002). No significant associations were found with fasting glycaemia, the 2 h OGTT, HbA1c, blood lipid profile, C-reactive protein, prolactin and waist circumference. Obesity (BMI >30 kg/m(2)) was associated with an increased risk of CM [odds ratio (OR) 2.4]. When the outcome of interest was the association between IR and obesity, the OR was significantly increased compared with IR alone (OR = 13.2). CONCLUSION: This may suggest that CM is associated with IR status, particularly when it is in partnership with obesity.

Stimulus-induced dissociation of neuronal firing rates and local field potential gamma power and its relationship to the resonance blood oxygen level-dependent signal in macaque primary visual cortex.

The functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi-unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network.

Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control.

Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache (MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine (EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings.

Reduced habituation of trigeminal reflexes in patients with episodic cluster headache during cluster period.

A growing body of evidence supports the pivotal role of the hypothalamus in the pathophysiology of cluster headache (CH). On the basis of animal studies, it has been suggested that a hypothalamic dysfunction can lead to a habituation deficit of brainstem reflex responses, as result of a stress-like condition. Taking into account these findings, we tested the hypothesis that habituation of brainstem reflexes may be impaired in CH patients. The habituation phenomenon of the late components (R2 and R3) of the blink reflex was studied in 27 CH patients during the cluster period, in 22 migraine patients interictally and in 20 control subjects. A significant habituation deficit in the R2 and R3 components was found in CH compared with both controls and migraineurs. The lack of habituation in CH, more pronounced than in migraine, points to abnormal processing of sensory stimuli at the trigeminal level that could be driven by hypothalamic dysfunction during the cluster period.

Improving adherence to highly active anti-retroviral therapy in Africa: the DREAM programme in Mozambique.

Ensuring high levels of adherence to highly active anti-retroviral therapy (HAART) is a priority in treating people living with AIDS. This study reports the rates of adherence of patients served by DREAM (Drug Resource Enhancement against AIDS and Malnutrition) in the city of Matola, Mozambique. DREAM, an innovative programme tailored for Africa, was implemented by the Community of Sant'Egidio in August 2001. DREAM provides patients with anti-retroviral drugs and laboratory tests at no charge, and is based on a particular strategy of health education and organization of services designed for a population that is predominantly poor and has a low level of formal education. This study analyzes the adherence of 154 patients over a period of 6 months. In evaluating adherence, two indicators were used: (1) the percentage of appointments kept for check-ups, tests and the collection of medicine, and (2) the overall change in the patients' blood chemistry over the 6-month period. Of the 154 patients, 127 (82.5%) kept more than 90% of their appointments. Adherence to the programme was further confirmed by a relevant increase of hemoglobin levels and CD4 counts, and a significant decrease in the viral loads among the 154 patients.

Abnormal head nociceptive withdrawal reaction to facial nociceptive stimuli in Parkinson's disease.

INTRODUCTION: Trigemino-cervical-spinal reflexes (TCSRs) are complex brainstem stereotyped nociceptive responses involved in a defensive withdrawal reaction of the head from facial nociceptive stimuli. OBJECTIVE: The present study was undertaken to collect data on possible TCSR abnormalities in idiopathic Parkinson's disease (PD) and investigate any correlation with motor signs and L-DOPA administration. METHODS: TCSRs were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the supraorbital nerve in 18 patients with PD and 24 controls. The latency (L) and area (A), as well as the sensory (ST), painful (PT) and reflex (RT) thresholds were measured during the 'off' and 'on' state, and possible correlations with the UPDRS III total score, selected subscores (tremor, neck rigidity, upper limb rigidity, akinesia, rising from a chair, posture and posture instability) and duration of illness were investigated. RESULTS: Significant changes between controls and PD patients were found in the L, A, PT and RT of TCSRs. These results were not significantly influenced by L-DOPA treatment. A significant correlation was found between neck rigidity, postural instability scores and duration of illness and the TCSR L and A values in PD patients in the 'off' state. CONCLUSIONS: TCSRs abnormalities, combined with dopamine resistance, are consistent with a primary loss of brainstem neurons mediating a complex sensory-motor integration including neck muscle tone and postural control as well as the head withdrawal reaction to the nociceptive stimuli. SIGNIFICANCE: TCSRs may represent a useful tool for the assessment of brainstem sensory-motor function in PD as well as other movement and degenerative disorders.

Morphologic and functional changes of the microlymphatic network in patients with advancing stages of primary lymphedema.

Using fluorescent microlymphography, we examined the morphology andfunctional characteristics of the microlymph-vascular network in 36 subjects including 9 patients with "compressible" lymphedema (Group I), 14 with minimally compressible lymphedema (Group II), 9 with noncompressible lymphedema (Group III), and 4 healthy individuals. As lymphedema progressedfrom early to advanced stages (Group I-III), an increasingly greater lymphatic capillary density and diameter were depicted and eventually fibrosis/sclerosis with lymphangiectasia, fragmentation and a gradual decrease in the number of microlymphatics. Concomitantly, there was a prolongation in transport and disappearance of fluorescent dye and a progressive increase in endolymphatic and interstitial hydrostatic pressures.

Lifetime prevalence of Bell's palsy in rural Bolivia: a door-to-door survey.

We carried out a door-to-door survey in rural areas of the Cordillera Province, Bolivia, to determine the prevalence of the most common neurological diseases in a sample of about 10,000 inhabitants. A team of non-doctor health workers administered a standard screening instrument for neurological diseases, a slightly modified version of the World Health Organization protocol. All subjects found positive at the screening phase underwent a complete neurological examination. On screening, we found 1,130 positive subjects, of whom 909 were aged 15 years and above. After the neurological examination, we found 52 cases who had experienced Bell's palsy during their life in the population aged 15 years and above. The lifetime prevalence on November 1, 1994 was 11.1/1,000 (95% confidence interval 7.8-14.5) for the population aged 15 years and above. The prevalence was higher in women than in men (13.7 and 8.7/1,000, respectively) and increased with age, reaching a peak in the group aged 65 years or more (31.7/1,000). Only 3 cases (5.8%) had received medical therapy.