RESUMO
The pedunculopontine nucleus (PPN) is a reticular nucleus located in the mesencephalic and upper pontine tegmentum. Initially, characterized by its predominant cholinergic projection neurons, it was associated with the "mesencephalic locomotor region" and "reticular activating system". Furthermore, based on histopathological studies, the PPN was hypothesized to play a role in the manifestation of symptoms in movement disorders such as Parkinson's disease (PD). Since axial symptoms represent unmet needs of PD treatments, a series of pioneering experiments in Parkinsonian monkeys promoted the idea of a potential new target for deep brain stimulation (DBS) and much clinical interest was generated in the following years leading to a number of trials analysing the role of PPN for gait disorders. This review summarizes the historical background and more recent findings about the anatomy and function of the PPN and its implications in the basal ganglia network of the normal as well as diseased brain. Classical views on PPN function shall be challenged by more recent findings. Additionally, the current role and future perspectives of PPN DBS in PD patients shall be outlined.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Núcleo Tegmental Pedunculopontino/fisiopatologia , HumanosRESUMO
BACKGROUND: After initial subarachnoidal hemorrhage (SAH), due to an intracranial aneurysm, rebleeding is known as a factor influencing the devastating outcome. This complication has been reported to occur in â¼ 4% of the patients admitted with aneurysmal SAH. Moreover, ultra-early rebleeding within the first 24 hours might occur in 9 to 17% of the cases (40-87% appearing in the first 6 hours). Risk factors influencing this situation include increasing aneurysm size, deterioration of neurologic deficits, angiography within 3 hours of bleeding, sentinel symptoms, and the loss of consciousness at initial bleeding. The aim of this retrospective study was to assess factors and potential risk factors related to rebleeding, specifically the interval from initial SAH to rebleeding. MATERIAL AND METHODS: From a consecutive series of 243 patients who experienced aneurysmal SAH, we identified 28 patients (11.5%; 12 men, 16 women; mean age: 58 ± 10 years) who developed in-hospital rebleeding during this 49-month study (2009-2013). Demographic, radiologic, and clinical characteristics including hemodynamic parameters were analyzed. RESULTS: Rebleeding was fatal in 20 of the 28 patients (71%) and caused severe neurologic deficits (Glasgow Outcome Scale: 3; modified Rankin Scale: 5) in 3 (29%) of the remaining 8 survivors. Rebleeding occurred within the first 4 hours in 15 patients (54%) within 7, 24, and 48 hours in 17 (61%), 6 (21%), and 1 (4%) patient, respectively. In this series, the medium arterial blood pressure was 98 ± 11 mm Hg at arrival at the emergency department, 88 ± 10 mm Hg before rebleeding, and it dramatically increased to 124 ± 22 mm Hg at rebleeding. For the patients with rebleeding after aneurysmal SAH, initial sentinel headache (79%) and loss of consciousness (68%) were the common presenting symptoms. The World Federation of Neurological Societies grade was documented on admission as follows: 1-3 (n = 14 [50%]); 4-5 (n = 14 [50%]). A Fisher grade 4 was documented in 82% of the cases on the initial computed tomography (CT) scan. Overall, 42% of the cases underwent endovascular (n = 6) or microsurgical occlusion of the aneurysm (n = 6). The rest of the patients (n = 16, 58%) did not underwent occlusion of the aneurysm because of poor clinical status. Digital substraction angiography was performed in 61% of the cases. CONCLUSION: Possible factors increasing the risk of in-hospital rebleeding after aneurysmal SAH are high systolic blood pressure, sentinel headache, initial loss of consciousness, poor Hunt and Hess grade, high Fisher grade on initial CT, large aneurysm size, and the performance of angiography. Most of the rebleedings in patients in our center are likely to occur within 7 hours after admission. Based on our findings, we suggest that mobilization of the patient and maneuvers including invasive procedures should be restricted to a minimum during intensive care unit treatment prior to the occlusion of the ruptured aneurysm. Stabilization of blood pressure with adequate sedation and analgesia prior to occlusion can be considered preventive strategies against rebleeding.