Francesco Latini

Brain Interstitial Nociceptin/Orphanin FQ Levels are Elevated in Parkinson's Disease

Expression and release of nociceptin/orphanin FQ (N/OFQ) are elevated in the substantia nigra reticulata of 6‐hydroxydopamine‐hemilesioned rats, suggesting a pathogenic role for N/OFQ in Parkinsons disease. In this study, we investigated whether elevation of N/OFQ expression in 6‐hydroxydopamine‐hemilesioned rats selectively occurs in substantia nigra and whether hypomotility following acute haloperidol administration is accompanied by a rise in nigral N/OFQ levels. Moreover, to prove a link between N/OFQ and idiopathic Parkinsons disease in humans, we measured N/OFQ levels in the cerebrospinal fluid of parkinsonian patients undergoing surgery for deep brain stimulation. In situ hybridization demonstrated that dopamine depletion was associated with increase of N/OFQ expression in substantia nigra (compacta +160%, reticulata +105%) and subthalamic nucleus (+45%), as well as reduction in caudate putamen (−20%). No change was observed in globus pallidus, nucleus accumbens, thalamus, and motor cortex. Microdialysis coupled to the bar test allowed to demonstrate that acute administration of haloperidol (0.8 and 3 mg/kg) increased nigral N/OFQ levels (maximally of +47% and +53%, respectively) in parallel with akinesia. A correlation with preclinical studies was found by analyzing N/OFQ levels in humans. Indeed, N/OFQ levels were found to be ∼3.5‐fold elevated in the cerebrospinal fluid of parkinsonian patients (148 fmol/ml) compared with nonparkinsonian neurologic controls (41 fmol/ml). These data represent the first clinical evidence linking N/OFQ to idiopathic Parkinsons disease in humans. They strengthen the pathogenic role of N/OFQ in the modulation of parkinsonism across species and provide a rationale for developing N/OFQ receptor antagonists as antiparkinsonian drugs.

New insights in the limbic modulation of visual inputs: The role of the inferior longitudinal fasciculus and the Li-Am bundle

Recent anatomical and DTI data demonstrated new aspects in the subcortical occipito-temporal connections. Although a direct (inferior longitudinal fasciculus, ILF) pathway has been previously described, its fine description is still matter of debate. Moreover, a fast and direct subcortical connection between the limbic system and the occipital lobe has been previously recognized in many functional studies but it still remains poorly documented by anatomical images. We provided for the first time an extensive and detailed anatomical description of the ILF subcortical segmentation. We dissected four human hemispheres with modified Klingler’s technique, from the basal to the lateral occipito-temporal surface in the two steps, tracking the ILF fibers until their cortical termination. Pictures of this direct temporo-occipital pathway are discussed in the light of recent literature regarding anatomy and functions of occipito-temporal areas. The dissection confirmed the classical originating branches of ILF and allowed a fine description of two main subcomponent of this bundle, both characterized by separate hierarchical distribution: a dorsal ILF and a ventral ILF. Moreover, a direct pathway between lingual cortex and amygdala, not previously demonstrated, is here described with anatomical images. Even if preliminary in results, this is the first fine description of ILF’s subcomponents. The complex but clearly segregated organization of the fibers of this bundle (dILF and vILF) supports different level of functions mediated by visual recognition. Moreover, the newly described direct pathway from lingual to amygdala (Li-Am), seems involved in the limbic modulation of visual processing, so it may support physiological conditions the crucial role of this connection in human social cognition. In pathological conditions, on the other hand, this may be one of the hyperactivated pathways in temporo-occipital epileptic and nonepileptic syndromes.

Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

Mobilization of the transcavernous oculomotor nerve during basilar aneurysm surgery: biomechanical bases for better outcome.

BACKGROUND: The transcavernous approach adds a significant exposure advantage in basilar aneurysm surgery. However, one of its frequently reported side effects is postoperative oculomotor nerve palsy. OBJECTIVE: To present the technique of mobilizing the oculomotor nerve throughout its intracranial course and to analyze its consequences on the nerve tension and clinical outcome. METHODS: The oculomotor nerve is mobilized from its mesencephalic origin to the superior orbital fissure. Its degree of mobility, related to the imposed pulling force, was measured in 11 cadaveric nerves. Tension was mathematically deduced and compared before and after mobilizing of the cavernous segment. One hundred four patients treated for basilar aneurysms with the orbitozygomatic pretemporal transcavernous approach were followed up for a 1-year period and evaluated for postoperative oculomotor nerve palsy. RESULTS: Releasing the transcavernous segment compared to cisternal mobilization alone resulted in a significant increase in freedom of mobility from 4 to 7.9 mm (P < .001) and in a significant decrease in tension from 0.8 to 0.5 N (P = .006). Ninety-nine percent of aneurysms treated with this technique were amenable to neck clipping, and a total of 84% of patients had a good postoperative outcome (modified Rankin Scale score, 0-2). All patients showed direct postoperative palsy; however, 97% had a complete recovery by 9 months. Only 3 patients had a persistent diplopia on medial gaze, which was corrected with prism glasses. CONCLUSION: Mobilization of the transcavernous oculomotor nerve results in better maneuverability and less tension on the nerve, which lead to successful surgical treatment and favorable oculomotor outcome.

How to avoid trivial mistakes during IPG replacement in patients treated with DBS for movement disorders: technical note from 13-years experience

Purpose: Recent data suggest how adverse events occur more frequently after Implantable Pulse Generator (IPG) replacement than during the deep electrode positioning in patients treated with Deep Brain Stimulation (DBS). For instance, erroneous extension adjustment to change in laterality and inaccurate lead connection represent problems, which strongly affect patients’ outcome. We analyzed our data after 13 years of IPG replacement. Materials and Methods: We treated 107 patients (83 PD and 24 Dystonia) with DBS in 13 years. The Dual Channel IPGs replaced during this period were 91. 25 patients needed more than one replacement, especially among the dystonic population. During surgery, we temporarily marked in all the cases the right extension lead before the disconnection from the exhausted IPG. Good impedances were intraoperatively checked in all the cases. Results: Our surgical technique allowed us to avoid any erroneous change in laterality or abnormal impedances due to a suboptimal connection to the IPG. The mean duration of the operation was 25 min and a quick postoperative restart of DBS was possible in all the cases. Stability of symptoms after IPG replacement was achieved in all the patients, with an accurate clinical management within the first 48–72 postoperative hours. Conclusion: Our surgical and postoperative management demonstrates how to avoid some important adverse events with some easy steps, without any discomfort for the patients in terms of duration of surgery or longer hospitalization. Thus, stability of symptoms after the IPG replacement may be easily guaranteed during the first postoperative period.

Epidural skull base approach for dural arteriovenous fistulas (DAVF) of the anterior and middle cranial fossa.

Epidural skull base approach for dural arteriovenous fistulas (DAVF) of the anterior and middle cranial fossa

Minimizing Collateral Brain Injury Using a Protective Layer of Fibrin Glue: Technical Note

BACKGROUND Neurosurgical procedures expose the brain surface to a constant risk of collateral injury. We describe a technique where the brain surface is covered with a protective layer of fibrin glue and discuss its advantages. METHODS A thin layer of fibrin glue was applied on the brain surface after its exposure in 34 patients who underwent different craniotomies for tumoral and vascular lesions. Data of 35 more patients who underwent standard microsurgical technique were collected as a control group. Cortical and pial injuries were evaluated using an intraoperative visual scale. Eventual abnormal signals at the early postoperative T2-weighted fluid-attenuated inversion recovery (T2FLAIR) magnetic resonance imaging (MRI) sequences were evaluated in oncological patients. RESULTS Total pial injury was noted in 63% of cases where fibrin glue was not used. In cases where fibrin glue was applied, a significantly lower percentage of 26% (P < 0.01) had pial injuries. Only 9% had injuries in areas covered with fibrin glue (P < 0.0001). Early postoperative T2FLAIR MRI confirmed the differences of altered signal around the surgical field in the two populations. CONCLUSION We propose beside an appropriate and careful microsurgical technique the possible use of fibrin glue as alternative, safe, and helpful protection during complex microsurgical dissections. Its intrinsic features allow the neurosurgeon to minimize the cortical manipulation preventing minor collateral brain injury.

Intraoperative Intratumoral Embolization of a Complex Recurrent Hemangiopericytoma: Technical Report and Review of the Literature.

Objective Recurrent brain tumors represent a challenge for neurosurgeons because of the extensive blood loss and the time needed for surgical resection. Only a few hemostatic agents are useful to prevent the bleeding and thus facilitate the surgical resection. Fibrin sealant can be used to achieve sealing, tissue adherence, or hemostasis when other means of hemostasis are inadequate or inappropriate. We report the feasibility and positive effects of direct intratumoral injection of fibrin sealant during resection of a recurrent hemangiopericytoma. Material and Methods The intraoperative intratumoral injection of fibrin sealant changed the tumor properties of a recurrent hemangiopericytoma of the tentorium with infra- and supratentorial extension. From a loose friable briskly bleeding tumor, this complex lesion became a nonbleeding well-demarcated soft-firm tumor that could easily be dissected off the pial surface and totally resected without extensive bleeding. Results There are several benefits of intratumoral injection of fibrin sealant in hemangiopericytomas: (1) the extensive bleeding is diminished and blood loss minimized; (2) the restriction of the surgical view by the venous oozing is diminished, making the microsurgical dissection of the tumor capsule off the pial surface easier and safer; (3) the loose consistency of the tumor becomes firmer and facilitates the manipulation of the tumor and leads to a safer resection; and (4) a shorter operating time is needed. Conclusion The use of intratumoral fibrin glue injection is a safe and useful technique that could be used for hemostasis of highly vascularized tumors to facilitate a safer resection and to reduce blood loss.