Paolo Ferroli

Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: First reported series

OBJECTIVE To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. METHODS Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long-term, high-frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. RESULTS Since this treatment, all five patients continue to be pain-free after 2 to 22 months of follow-up monitoring. Two of the five patients have remained pain-free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high-frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. CONCLUSION These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug-resistant chronic CHs. These data point to a central pathogenesis for chronic CHs.

Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis

OBJECTIVE To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. METHODS Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the “Istituto Nazionale Neurologico C Besta” in Milan. Limiting the review to the period 1991–6, to exclude the “learning period” (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. RESULTS Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1–7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12–39 months, mean 24 months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. CONCLUSIONS Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.

Presurgical Functional MR Imaging of Language and Motor Functions: Validation with Intraoperative Electrocortical Mapping

PURPOSE To prospectively determine the sensitivity and specificity of functional magnetic resonance (MR) imaging for mapping language and motor functions in patients with a focal mass adjacent to eloquent cortex, by using intraoperative electrocortical mapping (ECM) as the reference standard. MATERIALS AND METHODS The ethics committee approved the study, and patients gave written informed consent. Thirty-four consecutive patients (16 women, 18 men; mean age, 43.2 years) were included who met the following three criteria: They had a focal mass in or adjacent to eloquent cortex of the language or motor system, they had the ability to perform the functional MR imaging task, and they had to undergo surgery with intraoperative ECM. Functional MR imaging with verb generation (n = 17) or finger tapping of the contralateral hand (n = 17) was performed at 1.5 T with a block design and an echo-planar gradient-echo T2*-weighted sequence. Cortex essential for language or hand motor functions was mapped with ECM. A site-by-site comparison between functional MR imaging and ECM was performed with the aid of a neuronavigational device. Sensitivity and specificity were calculated according to task performed, histopathologic findings, and tumor grade. Exact 95% confidence intervals were calculated for each sensitivity and specificity value. RESULTS For 34 consecutive patients, there were 28 with gliomas, two with metastases, one with meningioma, and three with cavernous angiomas. A total of 251 cortical sites were tested with ECM; overall functional MR imaging sensitivity and specificity were 83% and 82%, respectively. Sensitivity (65%) was lower and specificity (93%) was higher in World Health Organization grade IV gliomas compared with grade II (sensitivity, 93%; specificity, 79%) and III (sensitivity, 93%; specificity, 76%) gliomas. At 3 months after surgery, language proficiency was unchanged in 15 patients; functionality of the contralateral arm was unchanged in 14 patients and improved in one patient. CONCLUSION Functional MR imaging is a sensitive and specific method for mapping language and motor functions.

Brainstem cavernomas: long-term results of microsurgical resection in 52 patients.

OBJECTIVE: To review the natural history and the long-term results of microsurgical resection of brainstem cavernous angiomas operated on in one institution. METHODS: A retrospective analysis was conducted of the preoperative and postoperative course in 52 consecutive patients who underwent microsurgical resection of a brainstem cavernoma between 1990 and 2002. The role of sex, age, cavernoma location, size, multiple bleedings, relationships to the pial-ependymal surface, surgical approach, and preoperative magnetic resonance imaging appearance were evaluated as prognostic factors possibly influencing outcome. Discrete data were compared by use of the &khgr;2 test and Fisher’s exact test as appropriate. RESULTS: The risk of hemorrhage was 3.8% per patient per year. The rebleeding rate was 34.7%. Nineteen of 29 patients who experienced new neurological deficits after surgery improved over time to their preoperative condition or better. Permanent morbidity was observed in 10 (19%) of 52 patients (follow-up: 1.5–10.5 yr; mean, 4.7 yr; median, 4.3 yr; standard deviation, 0.2 yr). The final Karnofsky Performance Scale score for these 10 patients was 90 in 2 patients, 80 in 2, 70 in 2, 60 in 2, 50 in 1, and 30 in 1. The mortality rate was 1.9%. The incidence of permanent new neurological deficits was lower in the 20 patients whose lesion could be removed through an anterolateral pontine approach (5 versus 29%; P = 0.035). CONCLUSION: Surgical resection is recommended for superficial lesions and for lesions that can be reached through the anterolateral pontine surface. Surgery is also recommended for symptomatic cavernomas with a satellite subacute hematoma.

Operative findings and outcomes of microvascular decompression for trigeminal neuralgia in 35 patients affected by multiple sclerosis

OBJECTIVE:The concept of vascular compression of the trigeminal root as the main etiological factor in idiopathic trigeminal neuralgia has achieved widespread acceptance, and microvascular decompression (MVD) is a well-established surgical procedure for its treatment. Multiple sclerosis (MS) has long been considered to be an absolute contraindication to MVD because of the supposed exclusive causative role of a demyelinating lesion affecting the trigeminal root entry zone. Magnetic resonance imaging preoperative identification of suspicious vessels along the cisternal course of the trigeminal nerve in MS patients raises the question of a possible causative role of vascular compression in MS patients. METHODS:We describe magnetic resonance imaging findings, surgical findings, and outcomes in 35 MS patients who underwent MVD for medically intractable trigeminal neuralgia. Results were assessed by clinical follow-up and periodic phone surveys. The mean follow-up was 44 months (range, 6–108 mo). RESULTS:Magnetic resonance imaging revealed the presence of demyelinating lesions affecting the brainstem trigeminal pathways of the painful side in 26 (74%) of 35 patients. During surgery, severe neurovascular compression at the trigeminal root entry zone was found in 16 (46%) of 35 patients. The long-term outcome was excellent in 39%, good in 14%, fair in 8%, and poor in 39% of patients. No statistically significant prognostic factor predicting good outcome could be found. There was no mortality, with a 2.5% long-term morbidity rate (facial nerve palsy in one patient). CONCLUSION:Results of MVD in trigeminal neuralgia MS patients are much less satisfactory than in the idiopathic group, indicating that central mechanisms play a major role in pain genesis.

Stimulation of the Posterior Hypothalamus for Medically Intractable Impulsive and Violent Behavior

Objective: To describe the therapeutic effect of deep brain stimulation for the treatment of patients with below-average IQs who are affected by aggressive and disruptive behavior and who are resistant to any drug and/or conservative treatment (including occupational therapy). Patients and Methods: Two consecutive patients suffering from mental retardation with aggressive and disruptive behavior and resistant to any pharmacological treatment underwent deep brain stimulation electrode placement in the posteromedial hypothalamus for continuous chronic high-frequency stimulation (HFS). The stereotactic coordinates of the target were chosen according to the study by Sano et al., which involved hypothalamic stereotactic lesions. Results: HFS of the posteromedial hypothalamus demonstrated consistent improvement of disruptive behavior in both patients at the follow-up evaluation 1 year later. Conclusions: HFS of the posteromedial hypothalamus showed similar results to those obtained by Sano et al. in the 1960s with radiofrequency lesions of the same target volume. The reversibility of neurostimulation allows HFS to control disruptive behavior when conservative treatments are ineffective, and drug therapy is uneventful or causes severe side effects. In conclusion, this neuromodulation procedure improved the quality of life and the range of social relationships for both of the treated patients.

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

OBJECT Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. METHODS The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. RESULTS The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. CONCLUSIONS Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

Application of Intraoperative Indocyanine Green Angiography for CNS Tumors: Results on the First 100 Cases

PURPOSE To investigate the application of indocyanine green (ICG) videoangiography during microsurgery for central nervous system (CNS) tumors. METHODS One hundred patients with CNS tumors who underwent microsurgical resection from December 2006 to December 2008 were retrospectively analyzed. The diagnosis was high grade glioma in 54 cases, low grade in 17 cases, meningioma in 14 cases, metastasis in 12 cases and hemangioblastoma in 3 cases. Overall, ICG was injected intraoperatively 194 times. The standard dose of 25mg of dye was injected intravenously and intravascular fluorescence from within the blood vessels was imaged through an ad hoc microscope with dedicated software (Pentero, Carl Zeiss Co., Oberkochen, Germany). Pre-resection and post-resection arterial, capillary and venous ICG videoangiographic phases were intraoperatively observed and recorded. RESULTS ICG videangiography allowed for a good evaluation of blood flow in the tumoral and peritumoral exposed vessels in all cases. No side effects due to ICG were observed. CONCLUSIONS ICG video-angiography is a significant method for monitoring blood flow in the exposed vessels during microsurgical removal of CNS tumors. Pre-resection videoangiography provides useful information on the tumoral circulation and the pathology-induced alteration in surrounding brain circulation. Post-resection examination allows for an immediate check of patency of those vessels that are closely related to the tumor mass and that the surgeon does not want to damage.

Endoscopic third ventriculostomy in idiopathic normal pressure hydrocephalus: An Italian multicenter study

OBJECTIVES The aim of the report is to define the indications and results of endoscopic third ventriculostomy (ETV) in idiopathic normal pressure hydrocephalus and to discuss the physiopathological mechanism of this procedure. METHODS The cases of 110 patients with idiopathic normal pressure hydrocephalus who underwent ETV in four Italian neurosurgical centers were retrospectively reviewed. The postoperative outcome was correlated with patient age, length of clinical history, preoperative clinical score, symptoms of clinical onset, type of hydrocephalus, and intraoperative findings. RESULTS The follow-up period ranged from 2 to 12 years (average, 6.5 yr). The outcome evaluation was made 2 years after the procedure. Postoperative clinical improvement occurred in 76 (69.1%) of 110 patients. There was no correlation between success rate and patient age or type of ventricular enlargement (normal or enlarged fourth ventricle). Conversely, the rate of neurological improvement was higher in patients with shorter clinical history, better preoperative neurological score, and clinical onset with gait disturbances. Moreover, the intraoperative finding of the sudden reappearance of normal cerebral pulsations and significant downward and upward movements of the third ventricular floor after ETV was also correlated with a good outcome. CONCLUSION ETV results in a relatively high rate of clinical improvement and a low complication rate in patients with idiopathic normal pressure hydrocephalus. Therefore, it may be easily performed with the same approach used for intracranial pressure monitoring with low morbidity. However, our data must be confirmed by additional studies.

A Simple Method to Assess Accuracy of Deep Brain Stimulation Electrode Placement: Pre-Operative Stereotactic CT + Postoperative MR Image Fusion

Objective: To describe a method for the measurement of the accuracy of deep brain stimulation (DBS) electrode placement with the use of image fusion technologies. Patients and Methods: Ten consecutive patients suffering from movement disorders underwent DBS electrode placement. Postoperative MR images were fused with the pre-operative stereotactic CT. The placement error in the anteroposterior, lateral and vertical planes was calculated. Results: The anteroposterior mean error ± SD was 0.61 ± 0.22 mm (range 0.2–0.9 mm). The lateral mean error ± SD was 0.65 ± 0.27 mm (range 0.2–2.2 mm). The vertical mean error ± SD was 0.82 ± 0.31 mm (range 0.3–1.6 mm). Conclusions: This technique provides a simple and precise method for the evaluation of the accuracy of DBS electrode placement.