The goal of this study was to determine the safety and efficacy of bilateral subthalamic region stimulation in the treatment of essential tremor (ET).
Following induction of general anesthesia, four ...patients with disabling tremor that had proved to be refractory to pharmacotherapy underwent magnetic resonance imaging-guided deep brain stimulation (DBS) of the bilateral subthalamic region. Tremor was assessed by applying the Fahn-Tolosa-Marń Tremor Rating Scale at baseline and again at the 12-month follow-up examination. Following surgery the total tremor score improved by 80.1% (from a baseline mean score of 63 +/- 15.1 to a score of 11.8 +/- 3.9 at 12 months postoperatively). There was a significant improvement (p < 0.0001) in the mean tremor score of the upper limb (postural and action component) from a baseline score of 3 +/- 0.9 to a score of 0.5 +/- 0.5 at 12 months postoperatively. In two patients with Score 4 head tremor complete arrest of the tremor was observed at 12 months. Motor function scores of the upper limb for drawing spirals, pouring water, and drawing lines improved significantly (p < 0.05) by 66.7, 76.9, and 58.3%, respectively. Handwriting improved by 68%, but this gain was not significant. The mean activities of daily living score at baseline was 20 +/- 3.2; there was an 88.8% improvement in this score to 2.3 +/- 1.5 at the 12-month evaluation. The voltage required for effective tremor control was low (mean 1.8 +/- 0.2 V) and, along with the other parameters of DBS (frequency and pulse width), did not change significantly over the 12-month period. Tolerance to the action component of tremor was not seen. There was no procedural or stimulation-related complication.
Bilateral subthalamic region stimulation is effective in arresting tremor and head titubation, as well as functional disability in ET. Complications like dysarthria and disequilibrium were not seen. These patients required low voltages of stimulation and did not develop a tolerance to the treatment.
A novel nanosomal paclitaxel lipid suspension (NPLS), free from Cremophor EL (CrEL) and ethanol, was developed to address the solvent-related toxicities associated with conventional paclitaxel ...formulation.
To evaluate the efficacy and safety of NPLS
CrEL-based paclitaxel (conventional paclitaxel) in patients with metastatic breast cancer (MBC).
A prospective, open-label, randomized, multiple-dose, parallel, phase II/III study.
Adult (18-65 years) female patients with MBC who had previously failed at least one line of chemotherapy were randomized (2:2:1) to NPLS 175 mg/m
every 3 weeks (Q3W,
= 48, arm A), NPLS 80 mg/m
every week (QW,
= 45, arm B) without premedication or conventional paclitaxel (Taxol
, manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m
Q3W (
= 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A (
= 37) or arm C (
= 17).
Pooled data from the primary study and its extension phase included 174 patients. The primary endpoint was the overall response rate (ORR). As per intent-to-treat analysis, ORR was significantly better in the NPLS QW arm as compared to conventional paclitaxel 44.4% (20/45)
22.7% (10/44), (
= 0.04). An improvement in ORR with NPLS Q3W
conventional paclitaxel arm 29.4% (25/85)
22.7% (10/44) (
= 0.53) was observed. Disease control rates observed were improved with NPLS Q3W
conventional paclitaxel Q3W (77.7%
72.7%,
= 0.66) and with NPLS QW
conventional paclitaxel Q3W (84.4%
72.7%,
= 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W
conventional paclitaxel Q3W arms.
NPLS demonstrated an improved tumor response rate and a favorable safety profile
conventional paclitaxel. NPLS 80 mg/m
QW demonstrated a significantly better response
conventional paclitaxel 175 mg/m
Q3W.
Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062).
Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target ...but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimize management of patients with complex pain symptomatology. However, previous attempts to stimulate multiple targets requires multiple trajectories and considerable expense. Using a single electrode to stimulate multiple targets would help overcome these challenges. A pre-requisite of such a technique is the ability to use different stimulation parameters at different contacts simultaneously on the same electrode. We describe a novel technique in 3 patients with chronic pain syndromes for whom conventional medical and/or neuromodulation therapy had failed using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies.
Quantum chemical calculations have been performed using HF, B3LYP, and MP2 methods on the model sulfonylurea PhSO2NHC(O)NHMe to understand the conformational and tautomeric preferences. The results ...indicate that a conformer with intramolecular hydrogen bond SLU-1 (hitherto not considered) is more stable than the conformer SLU-2 (which is generally considered) for sulfonylureas. The energy difference between these two conformers is about 4 kcal/mol in the gas phase; however, the energy differences between the two rotamers become negligible in the solvent phase. Iminol tautomeric forms of sulfonylurea (which were also not studied until now) are only about 5−6 kcal/mol higher in energy as per both gas-phase and solvent-phase analyses, indicating easy accessibility of tautomeric states in sulfonylureas. Quantum chemical analysis has also been carried out on the possible dimeric structures of these three important isomers of sulfonylurea, and correlations have been made to the known crystal structures of polymorphic states of sulfonylurea drugs.
Background: Several deep brain stimulation (DBS) targets have been explored for the alleviation of trigeminal anaesthesia dolorosa. We aimed to characterise the analgesia produced from the ...periaqueductal grey (PAG) and centromedian-parafascicular (CmPf) nucleus using a within-subject design. Method: We report a case series of 3 subjects implanted with PAG and CmPf DBS systems for the treatment of anaesthesia dolorosa. At follow-up, testing of onset and offset times, magnitude, and thermal and mechanical sensitivity was performed. Results: The mean pain score of the cohort was acutely reduced by 56% (p < 0.05) with PAG and 67% (p < 0.01) with CmPf stimulation at mean time intervals of 38 and 16 min, respectively. The onset time was 12.5 min (p < 0.05) for PAG stimulation and 2.5 min (p < 0.01) for CmPf. The offset time was 2.5 min (p < 0.05) for PAG and 12.5 min (p < 0.01) for CmPf. The two targets were effective at different stimulation frequencies and were not antagonistic in effect. Conclusion: The mechanisms by which stimulation at these two targets produces analgesia are likely to be different. Certain pain qualities may respond more favourably to specific targets. Knowledge of onset and offset times for the targets can guide optimisation of stimulation settings. The use of more than one stimulation target may be beneficial and should be considered in anaesthesia dolorosa patients.
Hyperactivity in the subthalamic nucleus (STN) is seen in animal models of Parkinson’s disease, and lesioning of the STN dramatically relieves the animal’s parkinsonism. Deep brain stimulation (DBS) ...of the STN is an effective treatment for patients with advanced Parkinson’s disease. We have studied the effects of a unilateral lesion placed in the STN in predominantly hemi‐parkinsonian patients. Twenty‐one patients with advanced idiopathic Parkinson’s disease were studied. Seventeen had asymmetrical tremor‐dominant Parkinson’s disease and four had bilateral disease. All patients underwent radiofrequency lesioning of the dorsolateral part of the STN under stereotactic guidance. The four patients with bilateral disease had, in addition, an electrode implanted contralaterally in the STN. Twenty‐one patients have been followed for a minimum of 12 months. Clinical evaluation included the use of the Unified Parkinson’s Disease Rating Scale (UPDRS) before and after surgery. Post‐operative high‐resolution MRI was performed in each patient to confirm lesion location, and this was correlated with clinical outcome. There was improvement in contralateral tremor, rigidity and bradykinesia in all patients followed for 6, 12 and 24 months, with the effect on tremor being greatest. l‐dopa equivalent daily intake was approximately halved, and this resulted in a significant reduction in dyskinesia. Psychometric test scores were mostly unchanged or improved. All lesions were successfully located in the dorsolateral STN. Nineteen of the 21 lesions extended beyond the STN to involve pallidofugal fibres (H2 field of Forel) and the zona incerta (ZI). Lesion‐induced dyskinesias were not a management problem except in one patient, whose lesion was confined to the STN. This patient was successfully treated with deep brain stimulator placement in the region of H2/ZI. Unilateral STN lesions can be made safely and are an effective alternative to thalamotomy, pallidotomy and unilateral STN DBS for the treatment of asymmetrical tremor‐dominant advanced Parkinson’s disease. Com bined lesioning of the dorsolateral STN and H2/ZI is particularly effective.
Cephalic arch stenosis (CAS) is a recently recognized cause of dysfunction in autogenous hemodialysis fistulas. The prevalence of this lesion among dysfunctional autogenous fistulas is described, as ...are outcomes after percutaneous therapy.
A cohort of 177 dysfunctional autogenous fistulas treated over a 48-month period was retrospectively analyzed for the presence of CAS. Of these, 116 (66%) were radiocephalic fistulas and 61 (34%) were brachiocephalic fistulas. CAS was identified in 26 fistulas among 24 patients. Fifty dilations and three stent placements in the cephalic arch were performed. Surveillance was conducted after percutaneous therapy by means of ultrasound dilution technique and measurement of dialysis flow rates. Patency rates were estimated with use of the Kaplan-Meier method. No patients were lost to follow-up.
The prevalence of CAS was 15% (26 of 177). There was a significant difference in the prevalence of CAS between brachiocephalic and radiocephalic fistulas (39% vs 2%; P <.001). High-pressure noncompliant balloon catheters were required in 29 of 50 dilations (58%) to efface the lesion. Primary patency rates (+/-SE) at 3, 6, and 12 months were 76% +/- 8, 42% +/- 10, and 23% +/- 9, respectively. Primary assisted patency rates (+/-SE) at 3, 6, and 12 months were 96% +/- 4, 83% +/- 8, and 75% +/- 10. Complications occurred in three cases (6%). A major complication with rupture of the cephalic arch resulted in thrombosis and fistula loss (n = 1); two minor complications of cephalic arch rupture were salvaged with placement of a Wallstent (n = 1) or prolonged balloon inflation (n = 1).
CAS is common among failing brachiocephalic arteriovenous fistulas. With aggressive percutaneous intervention and surveillance, favorable primary assisted patency rates can be achieved.
This study describes our experience in the surgical treatment of neuralgia of the glossopharyngeal and vagal nerves. Over the last 19 years, 21 patients underwent surgery. Their case notes were ...reviewed to obtain demographic information, clinical presentation, surgical findings and early results. All patients were then contacted by telephone for long-term results and complications. Independent analysis of results was carried out by a Neurology team. Ten patients had microvascular decompression (MVD). Four patients had MVD and nerve section. In the remaining seven patients, the glossopharyngeal and first two rootlets of the vagal nerve were sectioned. Nineteen (90%) of 21 patients experienced complete relief of pain immediately after surgery. The remaining patients reported an improvement in their symptoms. There were no mortalities. Four patients experienced short-term complications, which resolved. Two patients were left with a persistent hoarse voice. At follow-up (mean duration of 4 years), there was no recurrence in symptoms. In our experience, surgery is safe and effective for the treatment of vago-glossopharyngeal neuralgia.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the variability of the subthalamic nucleus (STN) size, orientation and target coordinates from direct visualization on high-resolution magnetic resonance (MR) images in patients undergoing ...surgical intervention for Parkinson's disease.
Sixty-six patients with Parkinson's disease were included in this study. The STN was visualized directly on high-resolution MR images, the size and orientation in both coronal and axial planes were recorded, as were the coordinates of the dorsolateral STN target in relation to the anterior-posterior commissural (AC-PC) line. The same STN target was defined in the Schaltenbrand atlas and atlas-based coordinates in proportion to the patient's AC-PC dimension were calculated. MR-imaging-based STN target coordinates were compared with the corresponding atlas-based coordinates.
Marked variation of STN size and orientation was observed. A significant difference was demonstrated on comparing left- and right-sided x and y coordinates. The comparison between MR-imaging-based and atlas-derived target coordinates demonstrated a significant difference in all directions except the left y coordinate.
This study demonstrates the substantial individual variability of STN size, orientation and target coordinates and a significant difference between target coordinates obtained by direct visual targeting on MR images and those obtained by indirect targeting based on atlases.
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