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.

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.

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.

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.

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.

Functional characterization of hypothalamic hyperprolactinemia.

PRL secretory dynamics were evaluated by several stimulation and suppression tests in nine patients with hyperprolactinemia due to organic hypothalamic disease. Basal PRL levels ranged between 20-63 ng/ml. There was a normal PRL response to TRH in eight cases (i.e. doubling of basal levels), whereas none of the seven tested subjects responded to sulpiride. The same dissociation of responses was not observed in any of the patients who were still hyperprolactinemic after surgery. Concomitant dopamine infusion resulted in sulpiride-induced PRL release in the four subjects so studied. None of 50 other hyperprolactinemic patients (11 with macroprolactinoma, 18 with microprolactinoma, and 21 with idiopathic hyperprolactinemia) showed PRL response to TRH but not to sulpiride. The TRH-induced PRL increase was significantly higher than that induced by sulpiride in hypothalamic hyperprolactinemia and significantly lower in idiopathic disease as well as in healthy controls; no differences were found in prolactinoma patients. The administration of substances resulting in stimulation of pituitary dopamine receptors, such as dopamine and L-dopa, induced a normal PRL suppression in 7 patients with hypothalamic disease so tested, whereas central nervous system-acting dopaminergic drugs, such as carbidopa plus L-dopa and nomifensine, failed to lower PRL levels in most cases (even when normoprolactinemic after surgery). These data suggest that the mild to moderate hyperprolactinemia found in many patients with hypothalamic lesions is due to dopamine deficiency at the pituitary level, that TRH and dopamine receptors at the lactotropes are intact in this condition, and that paired TRH and sulpiride tests may be of some diagnostic utility in hyperprolactinemic patients. They further suggest that subjects with so-called idiopathic hyperprolactinemia do not suffer from the type of hypothalamic derangement exhibited by patients with organic lesions of the hypothalamus.

Failure of nomifensine administration to discriminate between tumorous and nontumorous hyperprolactinemia.

It has recently been claimed that the PRL-lowering response to nomifensine administration (200 mg, orally) reliably discriminates patients with PRL-secreting tumors from those with so-called functional hyperprolactinemia. In the present study, this test was performed in 15 healthy controls, 7 hyperprolactinemic subjects without evidence of pituitary tumor, and 16 patients with prolactinoma. A decrease of serum PRL to below 65% of basal levels, which seemed to be the cut-off point in the previous study, was obtained in 11 subjects of the first group, in 4 subjects of the second group, and in 4 subjects of the third group. The decrease of mean serum PRL concentration after nomifensine was only significant in the first and second groups. Analysis of variance showed a significant difference in the PRL inhibition by nomifensine between the tumor group and the two groups without evidence of pituitary adenoma. Nevertheless, this study shows that the nomifensine test is unable to discriminate in the individual patient the tumorous or nontumorous origin of excessive PRL secretion.

Effects of ibopamine on serum prolactin and growth hormone levels in hyperprolactinemic and acromegalic subjects.

The effects of oral doses (100, 200, and 400 mg) of a dopamine derivative, ibopamine, on serum prolactin (PRL) and growth hormone (GH) levels were evaluated in hyperprolactinemic patients, some of whom also were acromegalic. There was dose-related lowering of PRL levels. The highest dose was as effective as 500 mg L-dopa, although the duration of action was shorter, with a decrease to below 50% of basal PRL values in all patients. Serum GH did not rise in nonacromegalic subjects, but it fell after 400 mg ibopamine in the L-dopa-sensitive acromegalic patients. These data suggest, but do not prove, that ibopamine is able to directly stimulate pituitary dopamine receptors.

Inhibition of prolactin release by serotonin antagonists in hyperprolactinemic subjects.

Metergoline (4 mg) and methysergide (3 mg), two serotonin antagonists known to inhibit prolactin secretion in normal subjects, and the dopaminergic agonist, bromocriptine (2.5 mg) were orally administered in hyperprolactinemic patients. Mean serum prolactin concentration was significantly decreased between 120 and 240 min following the ingestion of all three drugs in comparison with a placebo; a consistent reduction to below 50% of basal values occurred in 10 of 14 patients after metergoline, in 5 of 10 after methysergide, and in 11 of 14 after bromocriptine administration. These data indicate that serotonin antagonists may acutely lower serum prolactin levels in hyperprolactinemic patients similarly to bromocriptine, though their mechanism of action is most likely different.

Effects of chronic prazosin treatment on the renin-angiotensin-aldosterone system in man.

The effects of chronic prazosin treatment (3 mg/day for three weeks) on plasma renin activity (PRA) and plasma aldosterone (PA) levels were evaluated in 12 hypertensive patients, under conditions of metabolic balance. After three weeks of drug administration no significant change occurred in PRA as well as PA levels, with respect to pretreatment values, both in basal conditions and following 2 hours of ambulation. No change was observed in heart rate, while a fall in both systolic (P less than 0.02) and diastolic (P less than 0.05) blood pressure occurred in supine as well as in deambulation-stimulating condition. A mild increase in body weight (P less than 0.05) and a decrease in serum sodium (P less than 0.05) was induced by prazosin treatment. These findings are in keeping with the pharmacologic properties of prazosin, which is a selective blocker of postsynaptic alpha adrenoreceptors and therefore lowers vascular resistance without reflex sympathetic overactivity. The moderate volume expansion after prazosin does not appear to be aldosterone mediated.

Restoration of cyclic ovarian function by metergoline treatment in a patient with a prolactin-secreting pituitary microadenoma.

A patient with amenorrhea due to a prolactin-secreting pituitary microadenoma was treated with the antiserotoninergic drug metergoline for 8 months. The first menstruation occurred after 1 month of therapy, and it was followed by regular menses by the 3rd month. Presumptive evidence of ovulation was obtained in at least some instances by serum progesterone and gonadotropin determination. Serum prolactin was only slightly lowered by treatment. The patient had menses and possibly ovulation in the 2 months following drug withdrawal. Metergoline might restore ovarian function in hyperprolactinemic amenorrhea either by prolactin suppression or perhaps by direct stimulation of gonadotropin release.

Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline, and lisuride.

One hundred ninety-one hyperprolactinemic patients (78 women and 13 men; 54 with pituitary macroadenoma, 53 with microadenoma, and 84 with idiopathic disease) were treated for 2 to 48 months with one or two of the following prolactin (PRL)-lowering drugs: bromocriptine, metergoline, and lisuride. All of the three drugs used were highly effective in lowering PRL levels and restoring gonadal function both in females and in males in the majority of patients with either idiopathic or tumorous disease. In poorly responsive patients, increasing the drug doses resulted in further PRL lowering for all the three drugs. Mild side effects were frequently encountered with initiation of drug treatment but spontaneously subsided in most cases; severe side effects, necessitating stopping of the treatment, occurred in only 12 instances, but changing of the drug allowed PRL-lowering treatment to be continued in 11 of them.

Cerebral blood flow velocity and cerebrospinal fluid pressure after single bolus of propofol.

The effects of propofol on cerebral blood flow velocity, cerebrospinal fluid pressure, cerebral perfusion pressure and mean arterial pressure were studied during induction in 25 patients scheduled for elective craniotomy. Premedication consisted of only atropine sulphate 0.007 mg/kg (im) 45 min before induction. Measurements were made or derived at time zero and 1, 2, 3, 4 and 5 min after an induction dose of propofol (2.5 mg/kg). Patients were retrospectively stratified into two groups, according to cerebrospinal pressure basal values: (i) lower than 10 mmHg (10 pts) and (ii) higher than 10 mmHg (15 pts). Cerebral blood flow velocity, measured by transcranial Doppler, fell in all the patients, but the reduction was significant at 1, 2, 3 and 4 min only in the group with high CSF pressure, while it never reached the critical value of 10 cm/s. Cerebrospinal fluid pressure and mean arterial pressure decreased in both groups of patients and the fall reached a statistical significance at 1 and 2 min in the group with higher baseline CSF pressure, only at 1 min: a parallel decrease of CPP was recorded, but it was not significant. Thus propofol decreases CSF pressure without hazardous effects on cerebral blood velocity and on cerebral perfusion pressure and seems to be a suitable anaesthetic agent in controlling high cerebrospinal fluid pressure in neuroanaesthesia.

Isolated cervical juvenile xanthogranuloma in childhood.

STUDY DESIGN: This is a report of an exceptional case of isolated cervical juvenile xanthogranuloma in a child. OBJECTIVES: This case report draws attention to the fact that isolated xanthogranuloma of the central nervous system should be considered among possible diagnosis of subdural extramedullary spinal masses in children and young adults. SUMMARY AND BACKGROUND DATA: Isolated juvenile xanthogranuloma of the central nervous system is extremely rare. When located in the spinal canal it behaves like any extramedullary mass-occupying lesion. MRI depicts the tumor's association with adjacent structures. In cases in which a subtotal surgical removal was possible, radiotherapy has been indicated. METHODS: A three-year-old girl presented severe pain in the right shoulder and spastic tetraparesis. The MRI showed an intradural extramedullary mass homogeneously enhancing after DTPA-gadolinium infusion. Complete surgical removal of the tumor was performed through open-door laminoplasty. RESULTS: The child was pain free immediately after the surgical removal of the tumor. A gradual complete recovery of the neurologic deficits followed. Open-door laminoplasty provided sufficient operative space, and it minimized the impact on the growing spinal column. CONCLUSIONS: Isolated juvenile xanthogranuloma does not show any predilections of localization inside the central nervous system. Both intracranial and spinal juvenile xanthogranulomas appear isointense in MRI and enhance homogeneously with gadolinium. Whenever possible, total surgical removal alone seems to be curative. Otherwise, a subtotal removal of the tumor might be followed by radiotherapy. Immunohistochemical tests ensure the diagnosis.

Supracondyloid process and anomalous insertion of pronator teres as sources of median nerve neuralgia.

A case of median nerve entrapment at the elbow between the supracondyloid process and the anomalous origin of the pronator teres on it is presented. The anatomical variant and the histological background of this syndrome are outlined. The pathophysiology of the neuralgia is discussed. A relatively simple surgical procedure afforded complete relief of symptoms.