Predictive value of brain and vascular imaging including intracranial vessels in transient ischaemic attack patients: external validation of the ABCD3-I score.

BACKGROUND AND PURPOSE: Recently, brain and vascular imaging have been added to clinical variables to identify patients with transient ischaemic attack (TIA) with a high risk of stroke recurrence. The aim of our study was to externally validate the ABCD3-I score and the same score taking into account intracranial circulation. METHODS: We analyzed data from 1137 patients with TIA from the PROMAPA study who underwent diffusion-weighted magnetic resonance imaging (DWI) within 7 days of symptom onset. Clinical variables and diagnostic work-up were recorded prospectively. The end-points were subsequent stroke at 7 and 90 days follow-up. RESULTS: A total of 463 (40.7%) subjects fulfilled all inclusion criteria. During follow-up, eight patients (1.7%) had a stroke within 7 days, and 14 (3.1%) had a stroke within 3 months. In the Cox proportional hazard multivariate analyses, the combination of large-artery atherosclerosis and positive DWI remained as independent predictors of stroke recurrence at 7- and 90-day follow-up [HR 8.23, 95% confidence interval (CI) 2.89-23.46, P < 0.001]. The ABCD3-I score was a powerful predictor of subsequent stroke. The area under the receiver operating characteristic curve was 0.83 (95% CI 0.72-0.93) at 7 days and 0.69 (95% CI 0.53-0.85) at 90 days. When we include intracranial vessel disease in the score, the area under the curve increases but the difference observed was non-significant. CONCLUSION: The inclusion of vascular and neuroimaging information to clinical scales (ABCD3-I score) provides important prognostic information and also helps management decisions, although it cannot give a complete distinction between high-risk and low-risk groups.

Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores.

BACKGROUND: Several clinical scales have been developed for predicting stroke recurrence. These clinical scores could be extremely useful to guide triage decisions. Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients. METHODS: Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). A neurologist treated all patients within the first 48 h after symptom onset. The duration and typology of clinical symptoms, vascular risk factors and etiological work-ups were prospectively recorded in a case report form in order to calculate established prognostic scores. We determined the early short-term risk of stroke (at 7 and 90 days). To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. Cox proportional hazards multivariate analyses determining independent predictors of stroke recurrence using the different components of all clinical scores were calculated. RESULTS: We calculated clinical scales for 1,137 patients (90.6%). Seven-day and 90-day stroke risks were 2.6 and 3.8%, respectively. Large-artery atherosclerosis (LAA) was observed in 190 patients (16.7%). We could confirm the predictive value of the ABCD3 score for stroke recurrence at the 7-day follow-up [0.66, 95% confidence interval (CI) 0.54-0.77] and 90-day follow-up (0.61, 95% CI 0.52-0.70), which improved when we added vascular imaging information and derived ABCD3V scores by assigning 2 points for at least 50% symptomatic stenosis on carotid or intracranial imaging (0.69, 95% CI 0.57-0.81, and 0.63, 95% CI 0.51-0.69, respectively). When we evaluated each component of all clinical scores using Cox regression analyses, we observed that prior TIA and LAA were independent predictors of stroke recurrence at the 7-day follow-up [hazard ratio (HR) 3.97, 95% CI 1.91-8.26, p < 0.001, and HR 3.11, 95% CI 1.47-6.58, p = 0.003, respectively] and 90-day follow-up (HR 2.35, 95% CI 1.28-4.31, p = 0.006, and HR 2.20, 95% CI 1.15-4.21, p = 0.018, respectively). CONCLUSION: All published scores that do not take into account vascular imaging or prior TIA when identifying stroke risk after TIA failed to predict risk when applied by neurologists. Clinical scores were not able to replace extensive emergent diagnostic evaluations such as vascular imaging, and they should take into account unstable patients with recent prior transient episodes.

[Survival by surgical approach in patients with endometrial adenocarcinoma treated in Navarra in the 2001-2009]. / Supervivencia según vía de abordaje quirúrgico en pacientes con adenocarcinoma de endometrio tratadas en Navarra en el periodo 2001-2009.

BACKGROUND: Endometrial adenocarcinoma is the most frequent gynaecological neoplasia after breast cancer and represents 6% of cancers in women. The treatment for this disease is surgery. The majority of cases are diagnosed in their initial stages and surgery is curative; on other occasions it is necessary to add radiotherapy and chemotherapy. The classical treatment for endometrial adenocarcinoma is hysterectomy with double adnexectomy by laparotomy, with the addition of pelvic and para-aortic lymphadenectomy and omentectomy according to the characteristics of the case. During the last 10-15 years laparoscopy has been introduced in the surgical treatment of endometrial adenocarcinoma. The main aim of this study is to analyze the cases of endometrial adenocarcinoma treated surgically in the former Virgen de Camino Hospital (nowadays the Hospital Complex of Navarra) during 2001-2009. METHODS: Historical cohort of 444 patients with endometrial adenocarcinoma during 2001-2009 who received surgical treatment, followed four years. CONCLUSIONS: The results confirm that laparoscopy is a safe alternative to classical laparotomy as it does not affect either survival or time free of disease, in both endometrioid adenocarcinoma and non-endometrioid adenocarcinoma.

Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is rapidly becoming the preferred surgical choice for the treatment of advanced Parkinson's disease (PD). We report initial results in 15 patients after 12 months and in nine patients evaluated between 30 and 36 months postoperatively. Our experience confirms the robust antiparkinsonian effect of DBS of the STN in advanced PD. The severity of "off" episodes, as assessed by the Unified Parkinson Disease Rating Scale (UPDRS), was drastically reduced by 74% at 12 months, and dyskinesia scores (Dyskinesia Rating Scale) decreased. The levodopa daily dose was reduced by 55% at 12 months. A double-blind assessment to determine the effect of stimulation performed in nine patients at 3 months in the "off" medication condition was very significant (p<0.05). Nine patients have been followed for 3 years with maintained efficacy in the UPDRS "off" score and the dyskinesia score. The experience of other groups using a similar technique is reviewed. The overall assessment indicates a high antiparkinsonian effect of DBS of the STN even in advanced patients. The existence of a learning curve for this procedure should be taken into account when initial results are evaluated.

Stereotactic targeting of the globus pallidus internus in Parkinson's disease: imaging versus electrophysiological mapping.

OBJECTIVE: The reintroduction of pallidotomy for the treatment of Parkinson's disease (PD) has generated various opinions regarding the ideal anatomic or physiological location of the target within the globus pallidus. The role of microelectrode recording guidance in pallidotomy for the treatment of advanced PD is presently under debate. The purpose of this study was twofold. The first goal was to determine the degree of accuracy in the targeting of the globus pallidus internus (GPi) with magnetic resonance imaging (MRI), by comparing these results with the final placement of the thermolytic lesions (as defined by electrophysiological assessment). The second goal was to ascertain the somatotopic arrangement of the GPi in PD. METHODS: The analysis involved 50 patients with PD who underwent microrecording-guided pallidotomy. The theoretical coordinates for lesioning were calculated after definition of the intercommissural line by MRI. The actual placement of the lesions was determined after mapping of the GPi by microrecording, using stimulation to identify the sensorimotor region and its somatotopic organization. RESULTS: In most cases, the lesions were placed posterior and lateral to the targets chosen by MRI. Mapping by microrecording revealed differences of 2.3 +/- 1.55 mm and 3 +/- 1.9 mm in the mediolateral and anteroposterior coordinates, respectively. The actual lesion overlapped the theoretical target for only 45% of the patients. The somatotopic organization of the GPi was analyzed. Most of the units with sensorimotor activity or tremor-related activity were in the lateral portion of the nucleus. Upper limb and axial units were in the most lateral region and mainly in the ventral one-third of the nucleus. Lower limb responses were recorded mainly in the dorsal one-third of the nucleus. Tremor-related cells were found throughout the sensorimotor region of the nucleus. CONCLUSION: These results indicate that lesion targeting based on MRI alone is not sufficiently accurate to guarantee placement of the lesion in the sensorimotor region of the GPi.

Tardive akathisia due to sulpiride.

A 56 year-old woman who suffered from parkinsonism, oro-lingual dyskinesia (OLD) and tardive akathisia (TA) due to sulpiride is reported. OLD and TA appeared after sulpiride withdrawal. The patient was successfully treated with tetrabenazine even a mild parkinsonism was present. TA seems to be related with an apparent dopaminergic hyperactivity and it has to be differentiated of other neuroleptic-induced movement disorders such as restless legs syndrome in order of an appropriate treatment. Sulpiride has the same possible side effects than classic neuroleptics.

[Surgery of the subthalamic nucleus in Parkinson's disease]. / Cirugía del núcleo subtalámico en la enfermedad de Parkinson.

INTRODUCTION AND DEVELOPMENT: The subthalamic nucleus (STN) plays a crucial part in the pathophysiology of Parkinsonism. Its inactivation improves all the main signs and symptoms of Parkinson's disease. Surgery of the STN in patients with the disease is effective and the benefit/risk relationship very favorable. Although the dyskinesias are not a definite limitation, it seems most reasonable to use techniques of deep cerebral stimulation until greater experience has been obtained with subthalamotomy. The long term efficacy is being studied and preliminary data indicate that the clinical benefit obtained is maintained in the long term. CONCLUSIONS: More studies are necessary to determine the mechanism of action of surgery on the STN. The potential neuroprotector effect of subthalamic surgery requires more extensive study.

How predictors and patterns of stroke recurrence after a TIA differ during the first year of follow-up.

The highest risk of subsequent stroke after a TIA occurs within the first week after the index event. However, the risk of stroke recurrence (SR) remains high during the first year of follow-up. We studied the temporal pattern and predictors of SR (at 7 days and from 7 days to 1-year follow-up). Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). We determined the short-term (at 7 days) and long-term (from 8 days to 1 year) risk of SR. Patients who underwent short-term recurrence and long-term recurrence were compared with regard to clinical findings, vascular territories, and etiology. Enough information (clinical variables and extracranial vascular imaging) was assessed in 1,137 (90.6 %) patients. The 7-day stroke risk was 2.6 %. 32 (3.0 %) patients had an SR after 7-day follow-up. Multiple TIA (HR 3.50, 1.67-7.35, p = 0.001) and large artery atherosclerosis (HR 2.51, 1.17-5.37, p = 0.018) were independent predictors of early SR, whereas previous stroke (HR 1.40, 1.03-1.92, p = 0.034) and coronary heart disease (2.65, 1.28-5.50, p = 0.009) were independent predictors of late SR. Notoriously, 80 % of SR happened in the same territory of the index TIA at 7-day follow-up, whereas only 38 % during the long-term follow-up (p < 0.001). Different predictors of SR were identified throughout the follow-up period. Moreover, the ischemic mechanism differed in early and late stroke recurrences.

[Treatment of complicated Parkinson disease with a solution of levodopa-carbidopa and ascorbic acid]. / Tratamiento de la enfermedad de Parkinson complicada con una solución de levodopa-carbidopa y ácido ascórbico.

We prescribed a solution of levodopa-carbidopa and ascorbic acid (LCAAS) to 21 Parkinsonian patients with motor complications. Eight patients continued the treatment for a mean period of 16.8 months, experiencing substantial increases in the number of hours with good functional capacity. Bothersome symptoms such as dystonia and akathisia in off periods disappeared in all cases in which they had been present and LCAAS was tolerated (in 6 of the 8 patients who continued in the study and in 4 who abandoned treatment late). Intake of other anti-Parkinsonian drugs was reduced. Thirteen patients abandoned the study, citing exacerbation of biphasic dyskinesia as the main reason. We conclude that LCAAS is a useful therapy in some Parkinsonian patients whose motor complications are not managed with conventional drug treatment. Screening of patients is probably of utmost importance to ensure that LCAAS is not administered to patients who already suffer intense biphasic dyskinesia.

[Pathophysiological bases, clinical results and indications for surgical treatment in Parkinson disease]. / Bases fisiopatológicas, resultados clínicos e indicaciones del tratamiento quirúrgico de la enfermedad de Parkinson.

We review the present status of surgery for Parkinson's disease. Surgical options for Parkinson's disease are rapidly spanding. The main objectives of surgical techniques are to restore the dopaminergic deficit in the striatum (transplantation) and to normalize the neuronal activity of the subthalamic-pallidal circuit (pallidotomy and deep brain stimulation). Whereas cell transplantation is still considered an experimental procedure, ablative procedures and deep brain stimulation are widely used. Both types of surgical procedures are supported by strong scientific data. However, much work remains to be done in order to understand several aspects not clearly elucidated at present. The results and current indications for pallidotomy and deep brain stimulation are analyzed.

Surgical treatment of Parkinson's disease.

At present, there are three major surgical approaches to Parkinson's disease (PD): (1) Ablative surgery (i.e. pallidotomy, thalamotomy); (2) deep brain stimulation (DBS) of the thalamus, internal globus pallidus (GPi) and subthalamic nucleus (STN); and (3) grafting fetal mesencephalic cells into the striatum. As a result of increasing understanding of the pathophysiology of the basal ganglia and the demonstration of surgical alleviation of experimental parkinsonism, surgery has regained a paramount importance in the management of PD. The aim of pallidotomy and DBS is to reduce the excessive inhibitory output from the GPi and substantia nigra reticulata (SNr). Pallidotomy and DBS of the STN or GPi aim to reverse the pathophysiological consequences of dopamine deficiency in PD, and should be considered entirely symptomatic treatments. The ideal candidates for pallidotomy are young patients in good general health in whom dyskinesias are the main reasons for disability. Patients with severe bilateral problems uncontrollable with present pharmacological tools are candidates for DBS. As yet, there are no formal data to help decide how to choose between GPi and STN stimulation. In our practice, patients are allocated to GPi stimulation when 'on' dyskinesias are extremely severe. In most other instances, we prefer to perform STN stimulation. At present there is almost no reason to decide for the thalamic stimulation since tremor is equally arrested by STN stimulation, which in addition improves all other features of PD. Equally the only indication for thalamotomy would be a patient with long-standing tremor as the main clinical manifestation, which can not be controlled with drugs. The proportion of patients in whom the thalamus will be the preferable target for either DBS or thalamotomy is small (less than 5%). Grafting aims to repair the nigrostriatal pathway and restore dopaminergic function in the striatum. In the future implants containing not only dopaminergic cells but also growth factors and a variety of other substances could become a method to not only functionally compensate the biochemical abnormalities of PD but also to arrest its progression. This technique is limited to a few centres around the world owing to the technical, logistical and ethical problems of obtaining and handling embryonic cells. At present, grafting of dopaminergic cells is perhaps best suited for patients with young-onset PD (less than 45 years old) who are at high risk of developing complications within a short time of beginning pharmacological treatment and in whom the idea of making lesions or implanting electrodes into the brain for decades seems less appealing. Consideration of surgery in any given patient should be weighed against the risks (about 1% mortality and 2-6% of severe morbidity-hemiplegia, cognitive deficit, speech problems, etc.) associated with these techniques. The development of better imaging methods and the growing expertise of multidisciplinary teams will undoubtedly make surgery for PD safer and more effective in the future.

[Pallidotomy in the treatment of complicated Parkinson's disease: clinical results at two years and analysis of prognostic factors]. / Palidotomía en el tratamiento de la enfermedad de Parkinson complicada: resultados clínicos a los 2 años y análisis de factores pronósticos.

BACKGROUND: There is a renewed interest in pallidotomy as a treatment for complicated Parkinson's disease (PD). AIM: To present the clinical results as well as the analysis of prognostic factors obtained in 28 patients with PD and motor complications submitted to pallidotomy and followed by one year (n = 28) and 2 years (n = 12). RESULTS: The total motor score (Unified Parkinson's Disease Rating Scale [UPDRS]) in the off state improved by 33 and 23% at one and two years, respectively (p < 0.01). All the cardinal signs of the disease were significantly improved (p < 0.01): tremor (92%), rigidity (67%), bradykinesia (46%) and axial symptoms (21%). A slight tendency to worsening in axial symptoms was observed. Dyskinesias disappeared in all but one patient. The Schawb & England Scale in off was improved by 21%. No improvement in the non-operated side was observed. The subgroup of patients with an improvement of less than 30% in the UPDRS was older than the one with larger clinical benefit. The observed tendency to worsening in the total motor score was related mainly to the progression of the symptoms in the non-operated side. Complications were mild and transient. CONCLUSIONS: Pallidotomy is a relatively safe and effective therapeutic option for complicated PD patients. An adequate selection of patients is necessary, since efficacy is partial and limited to one hemibody.

[Stereotactic surgery in Parkinson's disease]. / Cirugía estereotáctica en la enfermedad de Parkinson.

Stereotactic surgery for Parkinson's disease (PD) has regained interest due to the recently described hyperactivity of the subthalamic-pallidal pathway. Many patients suffering from complications associated with the chronic use of levodopa may benefit from surgical treatments. There are different surgical targets and techniques (ablative and deep brain stimulation). The choice of one particular target and technique relies on the clinical symptoms of the patient. The risk/benefit ratio of surgery is related to the careful selection of patients and the technical accuracy. Intraoperative microrecording is considered the best method to avoid side effects and partial results. A series of patient's selection and follow-up assessment criteria are proposed.

Pallidotomy in Parkinson's disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study.

Supplementary motor area and right dorsal prefrontal cortex activation in Parkinson's disease is selectively impaired during volitional limb movements. Since posteroventral pallidotomy improves motor performance in Parkinson's disease patients 'off' medication (i.e. off medication for 9-12 h), we hypothesized that it would also concomitantly increase supplementary motor area and dorsal prefrontal cortex activation. Six Parkinson's disease patients with a median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5 (range 34-66) 'off' medication underwent unilateral right posteroventral pallidotomy. The patients had H2(15)O PET when 'off' medication before and 3-4 months after surgery. Each PET study comprised four to six measurements of regional cerebral blood flow either at rest or while performing regularly paced joystick movements in freely selected directions (forward, backward, left or right) using the left hand. Pre- and postoperative scans were performed in an identical manner and the associated levels of activation were compared using statistical parametric mapping. After pallidotomy, the median total motor UPDRS score 'off' medication decreased by 34.7% (P = 0.03) and mean response times of joystick movements following the pacing tones improved by 13.8% (P = 0.08). Relative increases in activation of the supplementary motor area and right dorsal prefrontal cortex were observed during joystick movements (P < 0.001). Decreased activation was seen in the region of the right pallidum (P = 0.001). We conclude that pallidotomy reduces pallidal inhibition of thalamocortical circuits and reverses, at least partially, the impairment of supplementary motor area and dorsal prefrontal cortex activation associated with Parkinson's disease.