With time on our side? Task-dependent compensatory processes in graceful aging.

Graceful aging has been associated with frontal hyperactivations in working- and episodic long-term memory tasks, a compensatory process, according to some, that allows the best normal elders to perform these tasks at a juvenile level, in spite of natural cortical impoverishment. In this study, 24 young and 24 healthy elderly participants were compared. Graceful aging was explored by investigating domains where most healthy elders perform like youngers (e.g. lexical-semantic knowledge) and tasks that are typically more challenging, like episodic long-term recognition memory tasks. With voxel-based morphometry, we also studied to what extent changes of fMRI activation were consistent with the pattern of brain atrophy. We found that hyperactivations and hypoactivations of the elders were not restricted to the frontal lobes, rather they presented with task-dependent patterns. Only hypoactivations and normal levels of activation systematically overlapped with regional atrophy. We conclude that compensatory processes associated with graceful aging may not necessarily be a sign of early saturation of executive resources, if this was to be represented by a systematic frontal hyperactivation, but rather they may represent the ability of recruiting new cognitive strategies. We discuss two possible approaches to further test this hypothesis.

Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study.

BACKGROUND: Worry is considered a key feature of generalized anxiety disorder (GAD), whose neural correlates are poorly understood. It is not known whether the brain regions involved in pathological worry are similar to those involved in worry-like mental activity in normal subjects or whether brain areas associated with worry are the same for different triggers such as verbal stimuli or faces. This study was designed to clarify these issues. METHOD: Eight subjects with GAD and 12 normal controls underwent functional magnetic resonance imaging (fMRI) mood induction paradigms based on spoken sentences or faces. Sentences were either neutral or designed to induce worry. Faces conveyed a sad or a neutral mood and subjects were instructed to empathize with those moods. RESULTS: We found that the anterior cingulate and dorsal medial prefrontal cortex [Brodmann area (BA) 32/23 and BA 10/11] were associated with worry triggered by sentences in both subjects with GAD and normal controls. However, GAD subjects showed a persistent activation of these areas even during resting state scans that followed the worrying phase, activation that correlated with scores on the Penn State Worry Questionnaire (PSWQ). This region was activated during the empathy experiment for sad faces. CONCLUSIONS: The results show that worry in normal subjects and in subjects with GAD is based on activation of the medial prefrontal and anterior cingulate regions, known to be involved in mentalization and introspective thinking. A dysregulation of the activity of this region and its circuitry may underpin the inability of GAD patients to stop worrying.

Contrast-enhanced MR imaging of brain lesions: a large-scale intraindividual crossover comparison of gadobenate dimeglumine versus gadodiamide.

BACKGROUND AND PURPOSE: The higher relaxivity of gadobenate dimeglumine compared with gadodiamide is potentially advantageous for contrast-enhanced brain MR imaging. This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative lesion enhancement. MATERIALS AND METHODS: Adult patients with suggested or known brain lesions underwent 2 identical MR imaging examinations at 1.5T, one with gadobenate dimeglumine and the other with gadodiamide. The agents were administered in randomized order separated by 3-14 days. Imaging sequences and postinjection acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, and global preference) and quantitatively for contrast-to-noise ratio (CNR). RESULTS: One hundred thirteen of 138 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumor, metastasis, extra-axial tumor, or other (47, 27, 18, and 21 subjects, respectively). Readers 1, 2, and 3 demonstrated global preference for gadobenate dimeglumine in 63 (55.8%), 77 (68.1%), and 73 (64.6%) patients, respectively, compared with 3, 2, and 3 patients for gadodiamide (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all qualitative end points and for CNR (increases of 23.3%-34.7% and 42.4%-48.9% [spin-echo and gradient-refocused echo sequences, respectively] for gadobenate dimeglumine compared with gadodiamide). Inter-reader agreement was good for all evaluations (kappa = 0.47-0.69). Significant preference for gadobenate dimeglumine was demonstrated for all lesion subgroup analyses. CONCLUSION: Significantly greater diagnostic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadodiamide at an equivalent dose.

Anatomy of the episodic buffer: a voxel-based morphometry study in patients with dementia.

In 2000 Baddeley proposed the existence of a new component of working memory, the episodic buffer, which should contribute to the on-line maintenance of integrated memory traces. The author assumed that this component should be critical for immediate recall of a short story that exceeds the capacity of the phonological store. Accordingly, patients with Alzheimer's dementia (AD) should suffer of a deficit of the episodic buffer when immediate recall of a short story is impossible. On the other hand, the episodic buffer should be somewhat preserved in such patients when some IR can occur (Baddeley and Wilson, 2002). We adopted this logic for a voxel-based morphometry study. We compared the distribution of grey-matter density of two such groups of AD patients with and of a group of age-matched controls. We found that both AD groups had a significant atrophy of the left mid-hippocampus; on the other hand, the anterior part of the hippocampus was significantly more atrophic in patients who were also impaired on the immediate prose recall task. Six out of ten patients with no immediate recall were spared at "central executive" tasks. Taken together our findings suggest that the left anterior hippocampus contributes to the episodic buffer of the revised working memory model. We also suggest that the episodic buffer is somewhat independent from the central executive component of working memory.

Angiographic follow-up of traumatic carotid cavernous fistulas treated with endovascular stent graft placement.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) of carotid cavernous fistulas (CCFs) is based on various techniques, mainly those using detachable balloons. Coronary covered stent grafts have been sporadically used in the intracranial arteries and only 2 traumatic CCFs have been reported in the literature; moreover, there is poor information about the long-term follow-up. We present 8 cases of CCFs treated by the placement of a covered stent, 5 of which have a 1-year clinical and angiographic follow-up. METHODS: Eight patients with posttraumatic CCF were treated by positioning a covered stent in the intracranial internal carotid artery (ICA) to occlude the fistula. They received periodic clinical and angiographic follow-up to evaluate the patency and the stability of clinical results. RESULTS: In all cases, the symptoms related to the CCF regressed after treatment and did not recur in the follow-up. Two patients presented residual filling of the CCF at the end of the procedure. The angiographic follow-up revealed in 6 patients of 7 a good patency of the ICA; in 1 patient, there was an ICA asymptomatic occlusion. One patient required transvenous coil occlusion of the cavernous sinus. CONCLUSION: When standard treatments fail, covered stent grafts can be used as a valid alternative in the treatment of CCFs, but more data are needed, especially in the long-term follow-up.

Left caloric vestibular stimulation ameliorates right hemianesthesia.

BACKGROUND: Left caloric vestibular stimulation (CVS) transiently reduces impairments of right-brain-damaged patients with left unilateral neglect, including left hemianesthesia, contralateral to the side of the lesion (contralesional). Conversely, no effect on right contralesional hemianesthesia in left-brain-damaged patients is seen with right CVS. This discrepancy is unexplained. METHODS: The authors explored the effect of CVS on right- and left-brain-damaged patients with hemianesthesia. One left-brain-damaged patient had an fMRI study during tactile stimulation before and after left CVS. The same fMRI touch study, without CVS, was performed in neurologically unimpaired subjects. RESULTS: A transient remission of right hemianesthesia associated with left brain damage was observed, provided that cold CVS was administered to the left ear. In the left-brain-damaged patient studied with fMRI, left CVS modulated the neural response to right hand tactile stimuli of a portion of the secondary somatosensory area (SII) of the right hemisphere. In neurologically unimpaired subjects, fMRI scans showed that the same part of area SII in the right hemisphere was activated by ipsilateral right-sided touches and to a larger extent than area SII in the left hemisphere by left-sided touches. CONCLUSIONS: Left caloric vestibular stimulation is effective on both left and right hemianesthesia because it modulates the hemisphere that has a more complete representation of, or is capable to attend to, the whole somatosensory surface of the body. These results suggest a hardwired hemispheric asymmetry in hand representation, starting from a somatotopically organized brain region such as area SII.

Preserved functional competence of perilesional areas in drug-resistant epilepsy with lesion in supplementary motor cortex: fMRI and neuropsychological observations.

We report a presurgical fMRI study and a longitudinal behavioral and structural MRI study in a 26-year-old right-handed woman with drug-resistant epilepsy of the supplementary motor region with cytoarchitectural dysplasia and minimal cortico-subcortical gliotic damage. fMRI scans were acquired during a silent phonemic verbal fluency task (VF), an automatic counting task (CT), and a finger-tapping motor task (MT). These were all compared with rest. Presurgical neuropsychological assessment was substantially normal with only a minor deficit in the domain of visuo-constructive and complex motor-planning skills. Noticeably, performance on phonemic verbal fluency was normal. Presurgical fMRI results revealed a normal specialization of left SMA and pre-SMA, including a fine-grained somatotopy for mouth and hand representations despite epilepsy. Immediately after surgical removal of the epileptogenic zone (the posterior third of the superior and middle frontal gyri including pre-SMA and part of SMA, and part of the anterior cingulate region--all of which were active presurgically at the fMRI tests), the patient suffered from transcortical motor aphasia temporarily. One year after surgery, she still showed impaired performance in the verbal fluency tasks while naming and comprehension were recovered. The patient was now free from seizures. This fMRI study supports the case that repeated seizures per se may not be sufficient to alter the distribution of neural representations of cognitive function. Selective behavioral impairment after surgical removal of brain areas that were activated during presurgical fMRI permits us to establish a causal link between these activations and task performance. This link could not have been made on the basis of activation patterns or lesion data taken on their own. These findings support the case that some epileptic patients may represent a unique opportunity for cognitive neuroscience studies.

Neuroimaging of focal cortical dysplasia: neuropathological correlations.

Focal cortical dysplasia is a well-known cause of intractable epilepsy with early onset of seizures, and is potentially amenable to surgical therapy. It was first described by Taylor in 1971 as a peculiar malformative disorganisation of the neocortex characterised at histology by loss of cortical lamination and accompanied by giant, dysmorphic neurones and, most frequently, by "balloon cells" littered throughout the cortex and sub-cortical white matter. While in the past decades the term "cortical dysplasia" has referred to various malformations of cortical development, such as agyria, pachygyria, polymicrogyria, heterotopia and hemimegalencephaly, it is now widely accepted that the entity identified by Taylor should be considered separately, from both histological and neuroimaging standpoints. More recently, the recognition of various histological subtypes of focal cortical dysplasia characterised by different degrees of cortical disruption with or without cytological abnormalities has generated several classifications that are still unsatisfactory. With better magnetic resonance capability, subtle and very small focal cortical dysplasias may now be visualised and the differential magnetic resonance aspects of the histological subgroups can be established. We will discuss the problem of histopathological classification and magnetic resonance imaging differentiation of the various subtypes of focal cortical dysplasia in the light of personal data collected from a large series of epileptic patients who underwent surgery and had a histological diagnosis of focal cortical dysplasia.

Pathophysiology, clinical manifestations and supportive care of metastatic brain cancer.

Brain metastases (BrM) are tumours that originate in tissues outside the central nervous system and spread secondarily to involve mainly the brain. The management of patients with cerebral metastases is complex, costly, and in some instances controversial. Furthermore, even in patients with widespread systemic cancer, the symptoms of the disease are often controllable while the symptoms of the BrM may be disabling. The treatment of BrM is one of the few areas of neuro-oncology where real progress has been made in the last twenty years. Moreover, the costs of managing this disease are rising, as therapies become more intensive and the number of patients with BrM increases. Modern neuroradiological imaging techniques, which are able to discover BrM earlier in the course of systemic cancer, and the greater efficacy of specific treatments, which lengthens survival, have increased the prevalence. The aggressive treatment of BrM may add some benefits to the patient, but its excessive cost leads to the necessity for accurate cost-effectiveness analysis. The latter begins with a complete understanding of the disease: its diagnosis, natural history and results of various modalities of treatment. While the development of BrM usually indicates a poor prognosis for the patient, advances in supportive care have made it possible to reverse most of the neurological symptoms and to give patients a meaningful extension of useful life.

Endovascular treatment with GDCs: results in 100 patients.

BACKGROUND: In this paper we review the clinical and morphological results of intracranial aneurysms treated with Guglielmi Detachable Coils. METHODS: We report our experience in 100 patients with intracranial aneurysms treated with GDC. Since February 1993 we have treated 70 females and 30 males, with a mean age of 57 years old, for a total of 118 intracranial aneurysms. Sixty-five patients had a recent history of ruptured aneurysm, 10 suffered from a previous subarachnoid hemorrhage and 25 patients had never bled. In the choice of treatment for subarachnoid aneurysm, in accordance with our neurosurgeons, we have not applied a protocol, rather we have followed guidelines in relation to: age, neurological clinical conditions, systemic disease and location of aneurysm. Morphological aspect of immediate aneurysm occlusion was: 60% more or less complete occlusion, 30% loose packing with 10% failures. RESULTS AND CONCLUSIONS: The clinical outcome at follow-up (1 month-3 years) was: 72 patients without neurological deficits, 19 patients improved pre-existing neurological deficits, 3 patients worsened for procedural complications; 6 patients died (1 patient unrelated).

Multidisciplinary (surgical and endovascular) approach to intracranial aneurysms.

In spite of the availability of the new endovascular technique (GDC) to manage cerebral aneurysms, to date, the crucial question "which is the proper treatment in a given patient?" still remains unsettled. In order to check whether an answer is possible, we retrospectively reviewed a personal series of 192 consecutive patients with cerebral aneurysms (1993-1995). We found 164 patients who had been considered eligible for active aneurysm treatment. Treatment modality has been chosen case by case on the basis of patient conditions, and aneurysm size and location. Four groups of patients were identified: Group 1: 104 patients (63.4%) with subarachnoid hemorrhage (SAH) in whom the treatment of choice was surgery; Group 2: 27 SAH patients (16.4%) in whom the first choice was GDC; Group 3: 7 SAH patients (4.2%) who died before the scheduled treatment; Group 4: 26 patients (15%) with not ruptured aneurysm who had either surgery or GDC. Based on the results of this series (improvement of the overall results through the multidisciplinary approach), we have developed the guidelines to prospectively manage future cases of cerebral aneurysms with the purpose to rationalize the management, thus further improving the overall results.

[Surgical versus endovascular treatment in cerebral aneurysm. The opinion of a neuroradiologist]. / Trattamento chirurgico o endovascolare dell'aneurisma cerebrale. Il parere del neuroradiologo.

Surgery is currently the treatment of choice for acutely ruptured aneurysms, representing an efficient option both in the short and long term. We believe that the endovascular option may be of help in high surgical-risk cases.

Surgical interruption of leptomeningeal drainage as treatment for intracranial dural arteriovenous fistulas without dural sinus drainage.

Intracranial dural arteriovenous fistulas (AVFs) have been recognized as acquired lesions that can behave aggressively depending on the pattern of venous drainage. Based on the type of venous drainage, they can be classified as fistulas drained only by venous sinuses, those drained by venous sinuses with retrograde flow in arterialized leptomeningeal veins, and fistulas drained solely by arterialized leptomeningeal veins. Serious symptoms, including hemorrhage and focal deficit, are related to the presence of arterialized leptomeningeal veins. In this paper, the authors report a consecutive series treated between 1988 and 1993 of 20 cases of intracranial dural AVFs with "pure leptomeningeal drainage." All patients underwent surgical interruption of the leptomeningeal draining veins. Based on the arterial supply, nine patients were managed by direct surgery, whereas 11 patients were prepared for surgery by means of preoperative arterial embolization. Radioanatomical cure of the fistula and good neurological recovery were achieved in 18 cases. Complete obliteration of the fistula was documented angiographically in two cases, but fatal hemorrhage occurred, probably due to partial thrombosis of the venous drainage. Based on this experience, the authors believe that surgical interruption of the draining veins is the best treatment option for intracranial dural AVFs. However, surgical results may be affected by the extension of postoperative thrombosis, which in turn may be related to the degree of preoperative venous engorgement.

Propofol anaesthesia in spontaneously breathing paediatric patients during magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the use of propofol to induce and maintain anaesthesia in spontaneously breathing paediatric patients (age 2 weeks-11 years) during Magnetic Resonance Imaging (MRI) of the CNS. METHODS: All patients were spontaneously breathing, without intubation, and received supplemental O2. Pulse rate, blood pressure (BP), electrocardiogram and EtCO2 were recorded in all patients, and in 38 subjects SpO2 was also monitored. Patients were divided in 2 groups according to their body weights: Group A (n = 34, bwt < or = 10 kg), and Group B (n = 48, bwt > 10 kg). RESULTS: Dosage of propofol during the time of induction (from insertion of the i.v. cannula to positioning on the MRI table) was significantly higher in smaller children (Group A; 5.4 +/- 2.2 (SD) mg/kg) as compared to children with bwt above 10 kg (Group B; 3.7 +/- 1.6 mg/kg). Propofol dosage for maintenance of anaesthesia was significantly higher in smaller children (Group A: 10.1 +/- 5.7 vs Group B: 7.1 +/- 3.0 mgkg-1 h-1, P = 0.003). During the time of induction, transient episodes of reduced BP (< or = 20%) occurred in 6 patients in Group A and 2 patients in Group B. During anaesthesia in Group B there was 1 episode of oxygen desaturation (95%), and 3 episodes of short and mild increases of EtCO2(< or = 52 mmHg). No other side effects occurred in any patient. MRI studies were successfully completed, only 3 sequences (Group A) had to be restarted. CONCLUSION: Propofol can be safely used for total intravenous anaesthesia in children undergoing MRI.

MR of corticotropin-secreting pituitary microadenomas.

PURPOSE: To assess the accuracy of MR in the preoperative identification of corticotropin-secreting pituitary microadenomas. METHODS: Twenty-six patients with clinical and biochemical evidence of pituitary-driven Cushing disease in whom MR of the seller region was performed were selected for this study. The MR examinations were retrospectively evaluated by a neuroradiologist who was aware of the presence of an adenoma at surgery but not of location and size of the lesion. RESULTS: Considering the whole group of MR examinations performed either without (n = 26) or without and with intravenous injection of gadopentetate dimeglumine (n = 16), overall 20 MR studies were judged to show disease. Seventeen of 26 microadenomas were adequately shown and located by MR (true-positive, 65.4%). In three cases the sides of the microadenomas were misjudged (false-positive, 11.5%). Six patients had negative MR studies (false-negative, 23%). Twelve of the 16 patients studied after gadopentetate dimeglumine injection had true-positive MR findings (75%). CONCLUSIONS: In our experience the accuracy of MR in detecting corticotropin-secreting microadenomas as small as 2 to 3 mm is 65% to 75%. Although precontrast images provide diagnostic information, the microadenoma can be better seen with administration of contrast material.

Inferior petrosal sinus sampling: evidence of a stimulatory effect of oCRH on GH secretion in Cushing's disease.

Preoperative localization of ACTH-secreting microadenomas has been performed in 9 patients with Cushing's disease by using bilateral and simultaneous venous sampling of the inferior petrosal sinuses. In addition to ACTH and PRL we determined GH levels after oCRH stimulation in order to confirm the possible occurrence of unilateral GH increases, as recently observed by us in one patient. A central-to-peripheral and an intersinus gradient of ACTH concentration was observed in all patients examined before and/or after oCRH stimulation. In 7 patients central-to-peripheral and side-to-side PRL gradients were recorded in basal conditions: in 5 of these patients a unilateral oCRH-induced PRL increase was observed. Six out of the 7 patients with unilateral PRL increases also showed an intersinus GH gradient in basal conditions (ratio greater than or equal to 1.5); in 5 of them a clearcut oCRH-induced GH increase was observed. A peripheral oCRH-induced GH and PRL increase was not observed in any of the patients. The observation of a paradoxical oCRH-induced GH increase in the inferior petrosal sinus with the higher ACTH concentration is of speculative and clinical interest; whether it reflects co-secretion of hormones by the tumour or hormone release by non-tumourous cells via paracrine mechanism is still to be clarified. The unilateral GH increase could represent an additional signal of the presence and localization of an ACTH-secreting tumour.

Bilateral and simultaneous venous sampling of inferior petrosal sinuses for ACTH and PRL determination: preoperative localization of ACTH-secreting microadenomas.

We report our experience on venous sampling of the inferior petrosal sinuses for basal and CRH-stimulated ACTH and PRL gradients in 8 patients with surgically proven Cushing's disease who had normal preoperative neuroradiological studies. In 7 patients basal plasma ACTH concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral sinus; the gradients were enhanced by oCRH administration. In one out of two patients who had previously undergone unsuccessful pituitary microsurgery, neither basal nor oCRH-induced ACTH increases led to correct localization of the microadenoma within the pituitary. In 4 out of 7 patients basal serum PRL concentrations in the inferior petrosal sinus ipsilateral to the tumor were higher than in the contralateral; only two out of 4 showed an increase in PRL levels after oCRH injection. Our study confirms that simultaneous and bilateral venous sampling of inferior petrosal sinuses is a valuable means to identify the site of microadenomas in patients with Cushing's disease without neuroradiological evidence of the tumor. This procedure may give misleading results in patients previously operated on. Unilateral or predominant increases of PRL concentration during catheterization of the inferior petrosal sinuses, when present, always lateralize to the side of the corticotroph adenoma, providing a possible additional signal of the presence of the tumor.

Intracerebral venous hemorrhage in "high-risk" carotid-cavernous fistula.

Intracerebral hematoma associated with carotid-cavernous fistula is a rare occurrence. Based on a review of the literature and on the analysis of personal observation, the authors define as "high-risk fistula" a carotid-cavernous fistula at risk of intracerebral hemorrhage. Characteristic features of these are computed tomography demonstration of parenchymal vermicular enhancement of brain vessels, and an angiographic pattern of dilated and tortuous cerebral veins. When an intracerebral hemorrhage occurs in a patient with carotid-cavernous fistula an early but phased and combined neuroradiological-neurosurgical approach is suggested as the best way to treat this life-threatening situation.

Morphological and blood flow MR findings in cerebral vascular malformations.

The authors report MR findings in 139 patients with 159 cerebral vascular malformations (36 arteriovenous malformations, 25 venous angiomas and 98 cavernous angiomas). Morphological aspects and hemodynamic findings due to rapid and slow flow are analysed. MR is able to differentiate the various type of lesions and permits the visualization of angiographically occult vascular malformations. In the case of cavernous angiomas MR information may not be sufficient for an absolute diagnosis because of differential diagnostic problems; correlation with the clinical history, CT and angiographic findings and follow-up MR study are certain to be necessary to increase specificity. Usually it is possible to distinguish histopathological components of the lesion and perilesional modifications in the cerebral parenchyma.