Peri-lead edema after deep brain stimulation surgery for Parkinson's disease: a prospective magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The aim of this study was to define the prevalence and characteristics of peri-electrode edema in a prospective cohort of patients undergoing deep brain stimulation (DBS) surgery and to correlate it with clinical findings. METHODS: We performed brain magnetic resonance imaging (MRI) between 7 and 20 days after surgery in 19 consecutive patients undergoing DBS surgery for Parkinson's disease. The T2-weighted hyperintensity surrounding DBS leads was characterized and quantified. Any evidence of bleeding around the leads was also evaluated. Clinical and follow-up data were recorded. In a subgroup of patients, a follow-up MRI was performed 3-6 weeks after surgery. We also retrospectively reviewed the post-operative computed tomography scans of patients who underwent DBS at our center since 2013. RESULTS: Magnetic resonance imaging showed a peri-lead edematous reaction in all (100%) patients, which was unilateral in three patients (15.8%). In six patients (31.6%), we detected minor peri-lead hemorrhage. Edema completely resolved in eight out of 11 patients with a follow-up MRI and was markedly reduced in the others. Most patients were asymptomatic but six (31.6%) manifested various degrees of confusional state without motor symptoms. We found no significant correlation between edema volume, distribution and any clinical feature, including new post-operative neurological symptoms. The retrospective computed tomography analysis showed that peri-electrode hypodensity consistent with edema is absent at early post-operative imaging but is common at scans performed >3 days after surgery. CONCLUSIONS: Peri-electrode edema is a common, transient reaction to DBS lead placement and a convincing relation between edema and post-operative clinical status is lacking.

Mechanical loading of intervertebral disc modulates microglia proliferation, activation, and chemotaxis.

OBJECTIVE: The aim of the study is to assess the effects of the neuroinflammatory microenvironment of a mechanically-induced degenerating intervertebral disc (IVD) on neuroinflammatory like cells such as microglia, in order to comprehend the role of microglial cells in degenerative disc disease. METHODS: Bovine caudal IVDs were kept in culture in an ex vivo bioreactor under high frequency loading and limited nutrition or in free swelling conditions as control samples. Conditioned media (CM) were collected, analysed for cytokine and neurotrophin content and applied to microglial cells for neuroinflammatory activation assessment. RESULTS: Degenerative conditioned medium (D-CM) induced a higher production of interleukin (IL)-8, nerve growth factor (NGF), interferon (IFN)-γ, IL-17 from IVD cells than unloaded control conditioned medium (U-CM). Upon 48 h of co-incubation with microglia, D-CM stimulated microglia proliferation, activation, with increased expression of ionized calcium binding adaptor molecule 1 (IBA1) and CD68, and chemotaxis. Moreover, an increment of nitrite production was observed. Interestingly, D-CM caused an upregulation of IL-1ß, IL-6, tumour necrosis factor α (TNFα), inducible NO synthase (iNOS), IBA1, and vascular endothelial growth factor (VEGF) genes in microglia. Similar results were obtained when microglia were treated with the combination of the measured cytokines. CONCLUSIONS: Our findings show that in IVD degenerative microenvironment, IL-8, NGF, IFN-γ, IL-17 drive activation of microglia in the spinal cord and increase upregulation of neuroinflammatory markers. This, in turn, enhances the inflammatory milieu within IVD tissues and in the peridiscal space, aggravating the cascade of degenerative events. This study provides evidence for an important role of microglia in maintaining IVD neuroinflammatory microenvironment and probably inducing low back pain.

Neurosurgical aspects of dialysis-related spinal amyloidosis: Report of three cases and a review of the literature.

BACKGROUND AND PURPOSE: Osteoarticular manifestations of beta-2 microglobulin amyloidosis are often diagnosed in long-term dialyzed patients. However, spinal involvement is rare (10-25% of patients), and generally not associated with neurological deterioration. Compression of the spinal cord or roots is extremely rare, and probably under-recognized. METHODS: The authors describe three cases of spinal stenosis presenting with neurological signs in long-term dialyzed patients, prospectively collected over 2 years in two different institutions and treated by surgical decompression. In all three cases, the main cause of neural compression was amyloid deposition in the spine, either extradurally in the ligamentum flavum or intradurally. RESULTS: All patients improved after surgery and did not present any postoperative complications. However, two out of three patients with amyloid in the cervical spine required surgical revision to obtain a satisfactory decompression of the spinal cord. DISCUSSION: The authors discuss spinal amyloidosis which is a well-known complication of long-term dialysis. However, neurological complications such as spinal cord or radicular symptoms have been rarely reported and, when present in dialyzed patients, are symptoms that are often attributed to other causes. To our knowledge, this is the first case series that demonstrates the relationship between neurological deterioration and amyloid depositions in the spinal canal that occur in long-term dialyzed patients. The prevalence of spinal stenosis related to the presence of amyloid in this specific subgroup of patients is probably underestimated.

Pituitary apoplexy: considerations on a single center experience and review of the literature.

PURPOSE: To present a single-center experience on pituitary tumor apoplexy and a review of literature focusing on predisposing and precipitating factors. METHODS: Clinical presentation of our series of cases. Contemporary published literature is also reviewed. RESULTS: The definition of this syndrome has not been consistent although now the majority of authors agree to definite it as an acute condition caused by hemorrhage or infarction of a pre-existing pituitary adenoma. Different predisposing and precipitating factors have been described in literature; among these antithrombotic and anticoagulant drugs, seem to play relevant roles. The clinical cases observed in our clinic confirm these data and suggest a probable association between elderly patients taking anticoagulant therapy and pituitary apoplexy adenoma. CONCLUSION: Pituitary tumor apoplexy remains a challenging disease in relation to difficulties in correct diagnosis and thus in appropriate treatment. Antithrombotic/anticoagulant therapy may have an important role as precipitating factor. When a pituitary disorder is known, great care should be taken in the prescription of anticoagulant therapy.

Factors affecting formation and rupture of intracranial saccular aneurysms.

Unruptured intracranial aneurysms represent a decisional challenge. Treatment risks have to be balanced against an unknown probability of rupture. A better understanding of the physiopathology is the basis for a better prediction of the natural history of an individual patient. Knowledge about the possible determining factors arises from a careful comparison between ruptured versus unruptured aneurysms and from the prospective observation and analysis of unbiased series with untreated, unruptured aneurysms. The key point is the correct identification of the determining variables for the fate of a specific aneurysm in a given individual. Thus, the increased knowledge of mechanisms of formation and eventual rupture of aneurysms should provide significant clues to the identification of rupture-prone aneurysms. Factors like structural vessel wall defects, local hemodynamic stress determined also by peculiar geometric configurations, and inflammation as trigger of a wall remodeling are crucial. In this sense the study of genetic modifiers of inflammatory responses together with the computational study of the vessel tree might contribute to identify aneurysms prone to rupture. The aim of this article is to underline the value of a unifying hypothesis that merges the role of geometry, with that of hemodynamics and of genetics as concerns vessel wall structure and inflammatory pathways.

The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk.

In western countries, the process of "ageing of the population" is increasingly forcing clinical medicine to find answers for pathologies affecting the elder segments of our community. In this respect, pituitary adenomas often raise difficult questions on surgical indications, since little is known about postoperative morbidity and mortality in elderly patients. The transsphenoidal endonasal approach (TNS), which is considered the gold standard for surgical resection of the majority of functioning and non-functioning pituitary adenomas, is supposed to be a low morbidity and mortality procedure in adult patients. However, only a few contradicting data are available in the literature about elderly patients. In this paper we retrospectively analyze a cohort of 43 consecutive patients aged more than 65 years, operated on for pituitary adenomas at our Institution in the years 1998-2007. These patients were treated by transsphenoidal endonasal approach (TNS) for resection of non-functioning pituitary adenomas (n = 31), GH-secreting adenomas (n = 4) and ACTH-secreting adenomas (n = 8). Clinical records reported a macroadenoma with tumour-related mass symptoms in about 80 % of patients; single or multiple pituitary deficits were present in 44 % of patients. Regarding comorbidities, cardiac disease was the most frequently observed (86 %); assessment of anaesthesiological risk indicated a moderate to severe ASA score in most patients, 11 % showing a 4-5 score. On the basis of current criteria, our retrospective analysis revealed that cure was achieved in 54 % of patients. The outcome was similar to that observed in the general population of patients undergoing transphenoidal surgery in our centre, without differences in the rate of surgical and endocrinological cure, minor and major surgical complications and hospitalization duration. In particular, no significant anaesthesiological complications were observed and no patient developed either permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. In conclusion, in specialized centres the surgical treatment of pituitary adenomas via the transsphenoidal route can be a safe and effective procedure even in elderly patients.

Subthalamic local field potential oscillations during ongoing deep brain stimulation in Parkinson's disease.

How deep brain stimulation (DBS) acts and how the brain responds to it remains unclear. To investigate the mechanisms involved, we analyzed changes in local field potentials from the subthalamic area (STN-LFPs) recorded through the deep brain macroelectrode during monopolar DBS of the subthalamic nucleus area (STN-DBS) in a group of eight patients (16 nuclei) with idiopathic Parkinson's disease. Monopolar STN-DBS was delivered through contact 1 and differential LFP recordings were acquired between contacts 0 and 2. The stimulating contact was 0.5 mm away from each recording contact. The power spectral analysis of STN-LFPs showed that during ongoing STN-DBS whereas the power of beta oscillations (8-20 Hz) and high beta oscillations (21-40 Hz) remained unchanged, the power of low-frequency oscillations (1-7 Hz) significantly increased (baseline=0.37+/-0.22; during DBS=7.07+/-15.10, p=0.0003). Despite comparable low-frequency baseline power with and without levodopa, the increase in low-frequency oscillations during STN-DBS was over boosted by pretreatment with levodopa. The low-frequency power increase in STN-LFPs during ongoing STN-DBS could reflect changes induced at basal ganglia network level similar to those elicited by levodopa. In addition, the correlation between the heart beat and the low-frequency oscillations suggests that part of the low-frequency power increase during STN-DBS arises from polarization phenomena around the stimulating electrode. Local polarization might in turn also help to normalize STN hyperactivity in Parkinson's disease.

Endoscopic treatment of colloid cysts of the third ventricle: long-term results in a series of 6 consecutive cases.

AIM: Colloid cysts of the third ventricle represent 0.5-2% of all intracranial tumors. Several surgical approaches have been proposed for the treatment of these lesions and endoscopy is the most recent one, but the best treatment still remains controversial. We decided to treat colloid cysts with endoscopic approach since 1999. In this paper we present our results in 6 consecutive cases admitted at our institution from 1999 to 2004. METHODS: There were 4 males and 2 females. The mean age was 51.6 (range 29-77). All the cysts were symptomatic. The presenting symptom was headache in 4 patients, gait disturbance in 2, altered vision in 2, mental status change in 2, urinary incontinence in 2, loss of consciousness in 2 and short-term memory loss in 1 patient. All the endoscopic procedures were performed via a right precoronal burr hole, with a rigid endoscope. RESULTS: The removal was radiologically complete in 4 cases and incomplete in 2. Overall outcome was good in all cases, with an improvement of colloid cyst-related hydrocephalus in all the patients. There was no surgical mortality. The mean follow-up period was 52.5 months. No tumor recurrences were observed. Complications occurred in only one patient: a septic ventriculitis, venous thrombosis of the right leg and pulmonary embolism developed, but completely resolved during the hospitalization time. CONCLUSION: The endoscopic approach for the removal of colloid cysts of the third ventricle represents a safe procedure, and can be considered a very good option for the treatment of these lesions.

Vertebral artery dissection in a child. Is "spontaneous" still an appropriate definition?

Though a rare cause of stroke in the general population, in almost one quarter of young patients affected by stroke cervical artery dissection (CAD) is the underlying cause. Among these cases "spontaneous" dissections, intended as non-traumatic, represent about 34% of posterior circulation arterial dissection in patients aged less than 18 years. We here describe the case of a seven-year-old boy who developed a spontaneous vertebral artery dissection (VAD) leading to occipito-mesial, thalamo-capsular and cerebellar infarction. Once a traumatic origin was excluded, clinical history and laboratory findings were further analysed: fever associated with tonsillitis during the previous week, raised inflammatory indices, a throat culture positive for beta haemolysing Streptococcus group A and high titres of streptococcal antibodies were found. This case suggests that patients with CAD referred as spontaneous deserve extensive analysis. Subjects presenting with a dissection and an underlying infection are likely to have a hyperinflammatory response (although further experience is needed). In these patients immediate start of antibiotic therapy, treatment with anti-inflammatory drugs and further a lifelong prophylaxis with antibiotics before any invasive procedure are strongly recommended.

Intradiploic frontal epidermoid cyst in a patient with repeated head injuries: is there a causative relationship?

Epidermoid cysts are rare disontogenetic tumoral lesions in the cranial compartment (1% of all intracranial tumors) and are usually located in relation to the cranial sutures; the intradiploic location is the less frequent. We report a clinical case in which the post-traumatic etiology of a frontal intradiploic epidermoid is considered. The histological findings revealed the presence of an epidermoid tumor associated with a typical foreign body inflammatory reaction, after repeated head traumas at the site of the tumour. This is the first case in whom the association between this tumoral lesion and a tissue inflammatory reaction due to foreign bodies is demonstrated.

Effect of cyclic adenosine 3',5'-monophosphate/protein kinase a pathway on markers of cell proliferation in nonfunctioning pituitary adenomas.

CONTEXT: Alterations in cAMP signaling have been identified as a cause of endocrine neoplasia. In particular, activating mutations of the G(s)alpha gene and protein kinase A (PKA) overactivity due to low expression of PKA regulatory subunit 1A (R1A) have been implicated in somatotroph proliferation. OBJECTIVE: The objective of this study was to evaluate the effects of cAMP-PKA cascade activation in nonfunctioning pituitary adenomas (NFPA). DESIGN AND METHODS: By immunohistochemistry, R1A, R2A, and R2B expression was evaluated in cells obtained from eight surgically removed NFPA positive for gonadotropins. Cyclin D1 expression and ERK1/2 activity were analyzed under basal conditions and after cAMP-PKA cascade activation. RESULTS: Immunohistochemistry studies demonstrated a low R1/R2 ratio in all NFPA. Additional unbalance of R1/R2 ratio by 8-chloroadenosine cAMP (8-Cl-cAMP) and direct adenylyl cyclase stimulation by forskolin did not increase cyclin D1 expression or ERK1/2 activity in five NFPA (group 1), but even caused 74 +/- 15% and 85 +/- 13% inhibitions of cyclin D1 and ERK1/2 activity, respectively, in the remaining NFPA (group 2). Moreover, in group 2, PKA blockade by the specific inhibitor PKI increased cyclin D1 expression (96 +/- 25% over basal) and ERK1/2 activity (116 +/- 28% over basal). CONCLUSIONS: These data show that in contrast with what was previously observed in transformed somatotrophs, activation of the cAMP-PKA pathway did not generate proliferative signals in tumoral cells of the gonadotroph lineage, and in a subset of tumors even exerted a tonic inhibitory effect, thus confirming a different role for the cAMP-mediated pathway in promoting proliferation in the pituitary.

Physiological recordings from electrodes implanted in the basal ganglia for deep brain stimulation in Parkinson's disease. the relevance of fast subthalamic rhythms.

Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain 126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significant 70 Hz activity was observed in only 2 of 11 nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the presence of 300 Hz oscillations. The two rhythms probably arise from different mechanisms, reflecting different functional and/or spatial aspects of subthalamic pathophysiology. Fast subthalamic oscillations could be exploited for intra-operative electrophysiological monitoring of the subthalamic nucleus, post-operative confirmation of electrode placement and patient-specific 'reglage' of the electrical parameters for chronic deep brain stimulation.

Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias.

The aim of this work was to study the role of subthalamo-pallidal synchronisation in the pathophysiology of dyskinesias. We recorded local field potentials (LFPs) in a patient with Parkinson's disease and left surgery induced dyskinesias with double, bilateral deep brain stimulation electrode implants in the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Synchronisation was studied through coherence analysis. In the nuclei contralateral to the dyskinetic side of the body there was decreased STN-GPi coherence in the high beta range (20-30 Hz) and an enhanced coherence at low frequencies (<10 Hz). Despite the possible limitations arising from single-case observations, our findings suggest that parkinsonian dyskinesias are related to altered synchronisation between different structures of the basal ganglia. Firing abnormalities within individual basal ganglia nuclei are probably not enough to account for the complex balance between hypokinetic and hyperkinetic symptoms in human parkinsonian dyskinesias and altered interactions between nuclei should also be considered.

The subthalamic nucleus in Parkinson's disease: power spectral density analysis of neural intraoperative signals.

To test a new tool for the neurophysiological identification of the human subthalamic nucleus (STN) during stereotactic surgery for the implantation of deep-brain-stimulation (DBS) electrodes, we analysed off-line the intraoperative signals recorded from patients with Parkinson's disease. We estimated the power spectral density (PSD) along each penetration track (8 patients, 13 sides) and determined the spatial correlation of the PSD with the target location estimated from neuroimaging procedures ("anatomical target"), and with the final target location derived from standard intraoperative neurophysiological procedures for STN localization ("clinical target"). At each step we recorded the 'on-line' signal for 120 seconds; because the PSD was estimated by calculating the periodogram for 6-second epochs of neural signal, we had 20 epochs at each step. When the electrode track crossed the STN, the PSD in the 0.25-2.5 kHz band increased, peaking on average <0.5 mm cranial to the clinical target and 1.00+/-1.51 mm caudal to the anatomical target. When the track was outside the nucleus, the PSD remained unchanged. Even on recordings with low signal-to-noise ratio, off-line PSD analysis of neural signals showed a good correspondence with the target indicated by the surgical team. On-line intraoperative estimation of the PSD may be a simple, reliable, rapid and complementary approach to electrophysiological monitoring during STN surgery for Parkinson's disease.

Intracranial metastasis of testicular seminoma in an HIV-positive. Case report and review.

We present what appears to be the first case of an intracranial metastasis from testicular seminoma in an HIV-positive patient. The computed tomography and magnetic resonance imaging appearance of the lesion mimicked meningioma or lymphoma. A significant increase in the risk of testicular seminoma has been reported in AIDS patients. Whenever there is lymph-node involvement upon diagnosis of testicular seminoma, intracranial metastases may appear. After surgical removal of an intracranial metastasis from testicular seminoma, radiotherapy should be considered. Chemotherapy is to be included in the treatment of intracranial metastases from testicular seminoma with systemic involvement.

300-Hz subthalamic oscillations in Parkinson's disease.

Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation.

AIM: Deep brain stimulation (DBS) is the treatment of choice for advanced Parkinson's disease. The target co-ordinates are traditionally calculated in relation to the intercommissural distance. Anterior (AC) and posterior commissures (PC) may be visualised by the means of ventriculography, CT or MRI. METHODS: We have studied the efficacy of direct visualisation of the subthalamic-red nucleus complex on MRI, the advantage of fusion of stereotactic CT and MR images (Multiple Sequences Image Fusion - MuSIF). These methods are combined with double check of indirect calculation of the target co-ordinates based on AC-PC line, as well as the corrispondence to the stereotactic electronic atlas. RESULTS: Subthalamic nucleus (STN) was well recognisable in fused images in all 22 sides. At 3 months from surgery it was possible to reduce 76% of L-dopa equivalent daily dose. Dyskine-sias reduced to 50% and motor fluctuation up to 45%. CONCLUSION: In our experience MuSIF offers very high rate of accuracy in calculation of target co-ordinates. Direct visualisation of STN in MR and MuSIF are reliable and facilitate the accuracy of identification of target co-ordinates. Intraoperative neurophysiological recording increases the accuracy of microelectrode position.

Do intraoperative microrecordings improve subthalamic nucleus targeting in stereotactic neurosurgery for Parkinson's disease?

AIM: The clinical importance of intraoperative microrecordings for subthalamic nucleus (STN) localization in neurosurgical practice remains a matter of debate in the various groups. METHODS: To investigate their usefulness in localizing the STN, we retrospectively evaluated how intraoperative microelectrode recordings changed the targeting of the STN estimated only on intraoperative stimulation and neuroanatomic targeting procedures. For neuroradiologic targeting of the nucleus we used a TC-MRI fusion algorithm and direct visualization of the STN. Besides standard microrecordings we also analyzed the power spectral density (PSD) pattern of physiological signals along the track and its neuroanatomic and clinical correlations. RESULTS: In our series of 12 patients with Parkinson's disease undergoing surgery for implantation of deep-brain stimulation (DBS) electrodes in the STN we found that in 25% (1/4) of patients, microrecordings determined the choice of the optimal track. In all the tracks analyzed the PSD peak coincided with the point selected for the final electrode implantation on the basis of the standard procedure for intraoperative monitoring based on both microstimulation and recordings. CONCLUSION: Intraoperative microrecordings are of determinant importance for accurate STN localization and are essential for optimal results in neurosurgical practice. PSD analysis is a simple and quick quantitative signal descriptor that will probably provide even more precise, simple and rapid tool for intraoperative neurophysiological localization of the STN.

Deep brain stimulation for Parkinson's disease: the experience of the Policlinico-San Paolo Group in Milan.

Thirty patients with idiopathic Parkinson's disease were treated with deep brain stimulation electrode in the subthalamic nucleus. After surgery, the patients' best mean Unified Parkinson's Disease Rating Scale (UPDRS III) scores (medictionOFF-stimulatorON versus preoperative medicationOFF) were 77+/-14% at 3 months ( n=20 patients) and 72+/-14% at 12 months follow-up ( n=16). The mean reduction in therapy (expressed in levodopa dose equivalents in mg) was 68+/-25% at 12 months. Postoperative complications were rare, mostly mild, and reversible. Therapeutic success depends on a multidisciplinary team approach, meticulous patient selection, including patients' cognitive, psychic, and behavioral status, and patient and family lifestyles.