Short- and long-term motor outcome of STN-DBS in Parkinson’s Disease: focus on sex differences

Neurological Sciences - Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD) with motor complications; the contribution...     

Paroxysmal itch caused by gain-of-function Nav1.7 mutation

Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Na_v1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.     

Assessment of left ventricular function by pulse wave analysis in critically ill patients

Purpose

Left ventricular (LV) performance is often quantified by echocardiography in critically ill patients. Pulse wave analysis (PWA) systems can also monitor cardiac function but in a continuous fashion. We compared echocardiographic and PWA-derived indices of LV function.

Methods

We enrolled 70 critically ill patients equipped with invasive arterial pressure monitoring who required echocardiography. We simultaneously assessed LV ejection fraction (LVEF), the rate of LV pressure rise during systole (dP/dt _MAX) obtained with echocardiography (EC-dP/dt _MAX), the ratio of effective arterial elastance to LV end-systolic elastance (E _a/E _es) determined by echocardiography, the dP/dt _MAX estimated from the arterial pressure waveform (AP-dP/dt _MAX) and the cardiac cycle efficiency (CCE) using PWA.

Results

Mean LVEF was 53 ± 18 % and CCE 0.16 ± 0.26. CCE was correlated linearly with LVEF (r = 0.88, 95 % CI 0.81 to 0.92, P < 0.001), and the dP/dt _MAX values from the two techniques were linearly correlated (r = 0.93, 95 % CI 0.87 to 0.96, P < 0.001). There was minimal bias between the techniques for measurement of dP/dt _MAX (23.7 mmHg/ms; 95 % CI ?23.6 to 71.0). E _a/E _es and CCE were inversely correlated (r = ?0.81, 95 % CI ?0.88 to ?0.71, P < 0.001). A CCE value of <0.07 predicted LVEF <40 % with a sensitivity of 0.93 and a specificity of 0.96 (AUC 0.98, 95 % CI 0.90 to 1.0, P < 0.001). A CCE value of >0.12 predicted LVEF ≥50 % with a sensitivity of 0.96 and a specificity of 0.82 (AUC 0.94, 95 % CI 0.87 to 1.0, P < 0.001). A CCE value <0.12 predicted E _a/E _es ≥1.3 with a sensitivity of 0.93 and a specificity of 0.89 (AUC 0.94, 95 % CI 0.83 to 1.0, P < 0.001).

Conclusions

PWA-derived variables provide relevant information on cardiac contractility and performance in critically ill patients. PWA provides an easy method for online hemodynamic evaluation in critically ill patients.     

Deep brain stimulation: Subthalamic nucleus electrophysiological activity in awake and anesthetized patients

Objective

The purpose of this study was to evaluate changes in subthalamic nucleus (STN) neuronal activity in Parkinson’s disease (PD) patients during deep brain stimulation (DBS) surgery under general anesthesia, and to compare these data with those recorded in the same subjects during previous surgery under local anesthesia.

Methods

Five patients with advanced PD, who had previously undergone bilateral STN-DBS under local anesthesia, underwent re-implantation under general anesthesia (with an anesthetic protocol based on the intravenous infusion of remifentanyl and ketamine) owing to surgical device complications. The microelectrode recording (MER) data obtained were analyzed by an off-line spike-sorting software. Neurophysiological data (number of spikes detected, mean firing rate, pause index and burst index) obtained under local and general anesthesia were then evaluated and compared by means of statistical analysis.

Results

We found no statistically significant difference between the first and second surgical procedures in any of the neurophysiological parameters analyzed.

Conclusions

Bilateral STN-DBS for advanced PD with MER guidance is possible and reliable under a ketamine-based anesthetic protocol.

Significance

General anesthesia can be proposed for those patients who do not accept an “awake surgery” for clinical reasons, such as excessive fear, poor cooperation or severe “off”-medication effects.     

Development of acute kidney injury during continuous infusion of vancomycin in septic patients

Purpose

Few data are available on the occurrence of renal failure during continuous infusion of vancomycin in critically ill patients.

Methods

We reviewed the data of all patients admitted to the intensive care unit (ICU) between January 2008 and December 2009 in whom vancomycin was given as a continuous infusion for more than 48 h in the absence of renal replacement therapy. We collected data on the doses of vancomycin and blood concentrations during therapy. Acute kidney injury (AKI) was defined as a daily urine output <0.5 ml/kg/h and/or an increase in the serum creatinine of ≥0.3 mg/dl from baseline levels during vancomycin therapy or within 72 h after its discontinuation. Multivariable logistic regression analysis was performed to identify predictors of AKI.

Results

Of 207 patients who met the inclusion criteria, 50 (24 %) developed AKI. These patients were more severely ill, had lower creatinine clearance at admission, were more frequently exposed to other nephrotoxic agents, had a longer duration of therapy, and had higher concentrations of vancomycin during the first 3 days of treatment (C _mean). The C _mean was independently associated with early AKI (within 48 h from the onset of therapy) and the duration of vancomycin administration with late AKI.

Conclusions

AKI occurred in almost 25 % of critically ill patients treated with a continuous infusion of vancomycin. Vancomycin concentrations and duration of therapy were the strongest variables associated with the development of early and late AKI during therapy, respectively.     

Short‐ and intermediate‐term efficacy of buprenorphine TDS in chronic painful neuropathies

Abstract Buprenorphine is a potent opioid available as a transdermal delivery system (TDS) formulation. This open‐label study investigated its safety, tolerability, and efficacy in 30 patients with chronic painful neuropathy. Subjects with visual analogue scale (VAS) score ≥5 under stable analgesic treatment were entered. The starting dosage of 35 μg/h was increased up to 70.0 μg/h in case of unsatisfactory pain control as assessed by fortnightly visits. The primary endpoint was the number of patients achieving at least 30% pain relief at day 42 visit. Treatment was safe over the study period. Nine patients dropped out for side effects, mostly nausea and daily sleepiness. Buprenorphine TDS was well tolerated in 21 patients. Thirteen patients achieved >30% of pain relief at day 42 visit. Five patients needed to increase the dosage to 52.5 μg/h. Eight patients did not meet the primary outcome, but none allowed increasing the dosage to 70 μg/h, and four patients withdrew consent to continue the study before day 42 visit because of a ‘fear to become addicted,’ although 40% had obtained VAS reduction. In our study, which needs to be confirmed by a controlled trial, buprenorphine TDS induced clinically meaningful pain relief in about 40% of patients with chronic painful neuropathy, suggesting its use as a third‐line treatment.     

Impaired cerebral and systemic hemodynamics under cognitive load in young hypotensives: a transcranial Doppler study

Reduced sympathetic outflow and deficits in cerebral hemodynamics have been considered as possible factors mediating the impaired cognitive performance in essential hypotension. However, the relationship between systemic blood pressure (BP), cerebral blood flow and cognitive functioning is still poorly understood. The present study was aimed at clarifying the physiological processes underlying cerebral and systemic hemodynamics in young hypotensives during cognitive engagement. Doppler sonography blood flow velocities in both middle cerebral arteries were measured from 17 hypotensives and 15 normotensives during a working memory task. Impedance cardiographic and BP measures were also recorded continuously. Lower increases in systolic and diastolic BP were observed in hypotensives. However, no evidence of lower sympathetic control was found for this group, as assessed by pre-ejection period. Flow velocity in middle cerebral arteries showed a lower increase in hypotensives throughout the task. Moreover, significant positive correlations between BP changes and blood flow velocities in middle cerebral arteries during the task were obtained for this group only, suggesting a less effective cerebral autoregulation. No difference was found between groups in task performance. Results suggest that during cognitive challenge hypotensives show impaired hemodynamic adjustments, both central and peripheral. However, such alterations do not directly affect cognitive performance, at least under moderate cognitive load.