Roberto Spreafico

Publications (60)201.73 Total impact

• Article: Heterotopic reelin in human nodular heterotopia: a neuropathological study.

  Laura Rossini, Laura Tassi, Roberto Spreafico, Rita Garbelli
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  ABSTRACT: Aim. The extracellular matrix glycoprotein reelin plays a crucial role in the control of neuronal migration and during development is expressed by Cajal-Retzius cells in the marginal zone. The purpose of this study was to investigate the possible involvement of reelin in the pathogenesis of human nodular heterotopia, a malformation of cortical development frequently associated with focal drug-resistant epilepsy. Methods. Five patients presenting with subcortical nodular heterotopia and referred for epilepsy surgery, after a comprehensive presurgical investigation, were considered. The surgical specimens were studied by combining immunohistochemistry, double immunofluorescence, and in situ hybridisation procedures. Results. The selected cases were characterised by the presence of multiple nodules presenting in the core cell-free zones, reminiscent of the cortical molecular layer. In all cases, small reelin-positive cells, without typical Cajal-Retzius cell features, were distributed inside the nodules and localised in these cell body-sparse regions. Conclusion. The presented data corroborate the hypothesis that reelin might be involved in human heterotopic nodular formation.
  Epileptic disorders: international epilepsy journal with videotape 12/2012; 14(4):398-402. · 1.50 Impact Factor
• Article: Electroclinical, MRI and surgical outcomes in 100 epileptic patients with type II FCD.

  Laura Tassi, Rita Garbelli, Nadia Colombo, Manuela Bramerio, Giorgio Lo Russo, Roberto Mai, Francesco Deleo, Stefano Francione, Lino Nobili, Roberto Spreafico
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  ABSTRACT: Focal cortical dysplasias (FCDs) are highly epileptogenic malformations associated with drug-resistant epilepsy, susceptible to surgical treatment. Among the different types of FCD, the type II includes two subgroups based on the absence (IIa) or presence (IIb) of balloon cells. The aim of this retrospective study was to investigate possible differences in electroclinical presentations and surgical outcomes between the two subgroups in 100 consecutive surgically treated patients with type II FCDs. All patients underwent a comprehensive presurgical assessment including stereo-EEG (SEEG) when necessary. No significant differences in gender, age at epilepsy onset, duration of epilepsy, age at surgery or seizure frequency were found between the two subgroups. Patients with type IIb FCD frequently showed sleep-related epilepsy. Their peculiar electrographic pattern was characterised by localised rhythmic or pseudo-rhythmic spikes or polyspikes ("brushes") enhanced during non-REM sleep and also associated with well-localised, brief, low-voltage fast activity. The incidence and frequency of short bursts of fast discharges, interrupted by activity suppression, increased during slow-wave sleep and often recurred pseudo-periodically. The occurrence of "brushes", present in 76% of the patients with type IIb FCD, was significantly associated (p<0.001) with the presence of balloon cells. We discuss the possible pathogenetic mechanisms underlying this activity. MRI diagnosis of type II FCD was made in 93% of the patients with balloon cells (BCs), suggesting that the presence of balloon cells might be, at least partially, responsible for the MRI features. Patients had very good postsurgical outcomes (83% in Engel class I) even after a long period of follow-up.
  Epileptic disorders: international epilepsy journal with videotape 09/2012; 14(3):257-66. · 1.50 Impact Factor
• Article: Blurring in patients with temporal lobe epilepsy: clinical, high-field imaging and ultrastructural study.

  Rita Garbelli, Gloria Milesi, Valentina Medici, Flavio Villani, Giuseppe Didato, Francesco Deleo, Ludovico D'Incerti, Michela Morbin, Giulia Mazzoleni, Anna Rita Giovagnoli, Annalisa Parente, Ileana Zucca, Alfonso Mastropietro, Roberto Spreafico
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  ABSTRACT: Magnetic resonance imaging-positive temporal lobe atrophy with temporo-polar grey/white matter abnormalities (usually called 'blurring') has been frequently reported in patients with temporal lobe epilepsy associated with hippocampal sclerosis. The poor distinction of grey and white matter has been attributed to various causes, including developmental cortical abnormalities, gliosis, myelin alterations, a non-specific increase in temporal lobe water content and metabolic/perfusion alterations. However, there is still no consensus regarding the genesis of these abnormalities and no histopathological proof for a structural nature of magnetic resonance imaging changes. The aim of this study was to investigate the pathological substrate of temporo-polar blurring using different methodological approaches and evaluate the possible clinical significance of the abnormalities. The study involved 32 consecutive patients with medically intractable temporal lobe epilepsy and hippocampal sclerosis who underwent surgery after a comprehensive electroclinical and imaging evaluation. They were divided into two groups on the basis of the presence/absence of temporo-polar blurring. Surgical specimens were examined neuropathologically, and selected samples from both groups underwent high-field 7 T magnetic resonance imaging and ultrastructural studies. At the clinical level, the two groups were significantly different in terms of age at epilepsy onset (earlier in the patients with blurring) and epilepsy duration (longer in the patients with blurring). Blurring was also associated with lower neuropsychological test scores, with a significant relationship to abstract reasoning. On 7 T magnetic resonance image examination, the borders between the grey and white matter were clear in all of the samples, but only those with blurring showed a dishomogeneous signal in the white matter, with patchy areas of hyperintensity mainly in the depth of the white matter. Sections from the patients with blurring that were processed for myelin staining revealed dishomogeneous staining of the white matter, which was confirmed by analyses of the corresponding semi-thin sections. Ultrastructural examinations revealed the presence of axonal degeneration and a significant reduction in the number of axons in the patients with blurring; there were no vascular alterations in either group. These data obtained using different methodological approaches provide robust evidence that temporo-polar blurring is caused by the degeneration of fibre bundles and suggest slowly evolving chronic degeneration with the redistribution of the remaining fibres. The article also discusses the correlations between the morphological findings and clinical data.
  Brain 06/2012; 135(Pt 8):2337-49. · 9.46 Impact Factor
• Article: Focal cortical dysplasia type IIa and IIb: MRI aspects in 118 cases proven by histopathology.

  Nadia Colombo, Laura Tassi, Francesco Deleo, Alberto Citterio, Manuela Bramerio, Roberto Mai, Ivana Sartori, Francesco Cardinale, Giorgio Lo Russo, Roberto Spreafico
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  ABSTRACT: This study aims to review the magnetic resonance imaging (MRI) aspects of a large series of patients with focal cortical dysplasia type II (FCD II) and attempt to identify distinctive features in the two histopathological subtypes IIa and IIb. We retrospectively reviewed the MRI scans of 118 patients with histological proven FCD IIa (n = 37) or IIb (n = 81) who were surgically treated for intractable epilepsy. MRI was abnormal in 93 patients (79 %) and unremarkable in 25 (21 %). A dysplastic lesion was identified in 90 cases (97 %) and classified as FCD II in 83 and FCD non-II in seven cases. In three cases, the MRI diagnosis was other than FCD. There was a significant association between the presence of cortical thickening (p = 0.002) and the "transmantle sign" (p < 0.001) and a correct MRI diagnosis of FCD II. MRI positivity was more frequent in the patients with FCD IIb than in those with FCD IIa (91 % vs. 51 %), and the detection rate of FCD II was also better in the patients with type IIb (88 % vs. 32 %). The transmantle sign was significantly more frequent in the IIb subgroup (p = 0.003). The rates of abnormal MRI results and correct MRI diagnoses of FCD II were significantly higher in the IIb subgroup. Although other MRI stigmata may contribute to the diagnosis, the only significant correlation was between the transmantle sign and FCD IIb.
  Neuroradiology 06/2012; 54(10):1065-77. · 2.82 Impact Factor
• Source

  Available from: Ingmar Blümcke

  Article: Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias.

  Roland Coras, Onno J de Boer, Dawna Armstrong, Albert Becker, Thomas S Jacques, Hajime Miyata, Maria Thom, Harry V Vinters, Roberto Spreafico, Buge Oz, [......], Marc Polivka, Felice Giangaspero, Dyah Fauziah, Jang-Hee Kim, Lei Liu, Wang Dandan, Jing Gao, Benjamin Lindeboom, Ingmar Blümcke, Eleonora Aronica
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  ABSTRACT: An International League Against Epilepsy (ILAE) consensus classification system for focal cortical dysplasias (FCDs) has been published in 2011 specifying clinicopathologic FCD variants. The aim of the present work was to microscopically assess interobserver agreement and intraobserver reproducibility for FCD categories among an international group of neuropathologists with different levels of experience and access to epilepsy surgery tissue. Surgical FCD specimens covering a broad histopathology spectrum were retrieved from 22 patients with epilepsy. Three surgical nonepilepsy specimens served as controls. A total of 188 slides with routine or immunohistochemical stainings were digitalized with a slide scanner to allow Internet-based microscopy review. Nine experienced neuropathologists were invited to review these cases twice at a time gap of 3 months and different orders of case presentation. The 2011 ILAE FCD consensus classification served as instruction. Kappa analysis was calculated to estimate interobserver and intraobserver agreement levels. In a third evaluation round, 21 additional neuropathologists with different experience and access to epilepsy surgery reviewed the same case series. Interobserver agreement was good (κ = 0.6360), with 84% consensus of diagnoses during the first evaluation (21 of 25 cases). Kappa values increased to 0.6532 after reevaluation, and consensus was obtained in 24 (96%) of 25 cases. Overall intraobserver reproducibility was also good (κ = 0.7824, ranging from 0.4991 to 1.000). Fewest changes in the classification were made in the FCD type II group (2.2% of 225 original diagnoses), whereas the majority of changes occurred in FCD type III (13.7% of 225 original diagnoses). In the third evaluation round, interobserver agreement was reflected by the level of experience of each neuropathologist, with κ values ranging from moderate (0.5056; high level of experience >40 cases/year) to low (0.3265; low level of experience <10 cases/year). Our study achieved a good and reliable interobserver agreement among the group of expert neuropathologists originally involved in the ILAE FCD consensus classification system. Intraobserver reproducibility in this group was even more robust. These results showed considerable improvement compared to a previous study evaluating the 2004 Palmini FCD classification. Agreement levels were lower in our second group of neuropathologists and were related to their level of access and experience with epilepsy surgery specimens. These results suggested that the more precise ILAE definition of FCD histopathology patterns improves operational procedures in the diagnosis of FCDs. On the other hand, microscopic assessment of FCD is a challenge and requires sustained experience and teaching. The virtual slide review system allowed testing of this hypothesis and reached a widespread group of participating colleagues from different centers all over the world. We propose to further use this tool as a teaching device and also to address other epilepsy-associated entities still difficult to classify such as hippocampal sclerosis, long-term epilepsy-associated tumors, or mild malformations of cortical development (mMCDs), which were not yet covered by current ILAE classification systems.
  Epilepsia 05/2012; 53(8):1341-8. · 3.96 Impact Factor
• Article: Malformations of cortical development.

  Eleonora Aronica, Albert J Becker, Roberto Spreafico
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  ABSTRACT: Structural abnormalities of the brain are increasingly recognized in patients that suffer from pharmacoresistant focal epilepsies by applying high-resolution imaging techniques. In many of these patients, epilepsy surgery results in control of seizures. Neuropathologically, a broad spectrum of malformations of cortical development (MCD) is observed in respective surgical brain samples. These samples provide a unique basis to further understand underlying pathomechanisms by molecular approaches and develop improved diagnostics and entirely new therapeutic perspectives. Here we provide a comprehensive description of neuropathological findings, available classification systems as well as molecular mechanisms of MCDs. We emphasize the recently published ILEA classification system for focal cortical dysplasias (FCDs), which are now histopathologically distinguished as types I to III. However, this revised classification system represents a major challenge for molecular neuropathologists, as the underlying pathomechanisms in virtually all FCD entities will need to be specified in detail. The fact that only recently, the mammalian target of rapamycin (mTOR)-antagonist Everolimus has been introduced as a treatment of epilepsies in the context of tuberous sclerosis-associated brain lesions is a striking example of a successful translational "bedside to bench and back" approach. Hopefully, the exciting clinico-pathological developments in the field of MCDs will in short term foster further therapeutic breakthroughs for the frequently associated medically refractory epilepsies.
  Brain Pathology 05/2012; 22(3):380-401. · 3.99 Impact Factor
• Article: Cause matters: a neuropathological challenge to human epilepsies.

  Ingmar Blümcke, Roberto Spreafico
  Brain Pathology 05/2012; 22(3):347-9. · 3.99 Impact Factor
• Article: Epileptogenic networks of type II focal cortical dysplasia: a stereo-EEG study.

  Giulia Varotto, Laura Tassi, Silvana Franceschetti, Roberto Spreafico, Ferruccio Panzica
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  ABSTRACT: In the context of focal and drug-resistant epilepsy, surgical resection of the epileptogenic zone may be the only therapeutic option for reducing or suppressing seizures. In many such patients, intracranial stereo-EEG recordings remain the gold standard for the epilepsy surgery work-up. Assessing the extent of the epileptogenic zone and its organisation is a crucial objective, and requires advanced methods of signal processing. Over the last ten years, considerable efforts have been made to develop signal analysis techniques for characterising the connectivity between spatially distributed regions. The aim of this study was to evaluate the changes in dynamic connectivity pattern under inter-ictal, pre-ictal and ictal conditions using signals derived from stereo-EEG recordings of 10 patients with Taylor-type focal cortical dysplasia. A causal linear multivariate method - partial directed coherence - and indices derived from graph theory were used to characterise the synchronisation property of the lesional zone (corresponding to the epileptogenic zone in our patients) and to distinguish it from other regions involved in ictal activity or not. The results show that a significantly different connectivity pattern (mainly in the gamma band) distinguishes the epileptogenic zone from other cortical regions not only during the ictal event, but also during the inter- and pre-ictal periods. This indicates that the lesional nodes play a leading role in generating and propagating ictal EEG activity by acting as the hubs of the epileptic network originating and sustaining seizures. Our findings also indicate that the cortical regions beyond the dysplasia involved in the ictal activity essentially act as "secondary" generators of synchronous activity. The leading role of the lesional zone may account for the good post-surgical outcome of patients with type II focal cortical dysplasia as resecting the dysplasia removes the epileptogenic zone responsible for seizure organisation. Furthermore, our findings strongly suggest that advanced signal processing techniques aimed at studying synchronisation and characterising brain networks could substantially improve the pre-surgical evaluation of patients with focal epilepsy, even in cases without an associated anatomically detectable lesion.
  NeuroImage 04/2012; 61(3):591-8. · 5.89 Impact Factor
• Article: Epilepsy and NREM-parasomnia: a complex and reciprocal relationship.

  Alessandro Pincherle, Paola Proserpio, Giuseppe Didato, Elena Freri, Suela Dyljgeri, Tiziana Granata, Lino Nobili, Roberto Spreafico, Flavio Villani
  Sleep Medicine 01/2012; 13(4):442-4. · 3.40 Impact Factor
• Article: Cortical malformations.

  Roberto Spreafico, Laura Tassi
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  ABSTRACT: The formation of the normal human cortex is the result of complex, precisely timed sequences of processes taking place during embryogenesis and any insult (either genetic or environmental) involving one or more of the leading processes of corticogenesis may result in cortical malformation. Malformations of cortical development (MCDs) are defined in their broadest sense as malformative lesions of the cortex resulting from derangements of normal processes that take place during the first two trimesters of human pregnancy and involve cells that, under normal circumstances, participate in the formation of the cortical mantle. The etiology of malformative disorders is often uncertain and the mechanisms by which they generate epilepsy and neurological disorders are not completely understood; however, over the past decade, molecular, biological and genetic studies of cortical development have greatly expanded our knowledge of the normal mammalian brain's development and derangements. Several disorders of cortical development have been recognized, and for some of them specific causative genetic defects have been identified. Although the precise incidence of MCDs is not known, it appears that they are more common than recognized in the pre-magnetic resonance imaging era, particularly in patients with epilepsy since MCDs can be intrinsically epileptogenic, presumably owing to an abnormal rearrangement of the intralesional circuitry. In this chapter the major cortical malformations, their classification, their possible etiology, and their involvement in generating epileptic seizures and epilepsy syndromes are presented.
  Handbook of Clinical Neurology 01/2012; 108:535-57.
• Article: Sleep breathing disorders in 40 Italian patients with Myotonic dystrophy type 1.

  Alessandro Pincherle, Vincenzo Patruno, Paola Raimondi, Sabrina Moretti, Ambra Dominese, Filippo Martinelli-Boneschi, Maria Barbara Pasanisi, Eleonora Canioni, Franco Salerno, Francesco Deleo, Roberto Spreafico, Renato Mantegazza, Flavio Villani, Lucia Morandi
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  ABSTRACT: The aim of this study was to estimate the prevalence and nature of sleep breathing disorders in Myotonic dystrophy type 1 (DM1). We wanted to determine whether there is a relationship between sleep breathing disorders and clinical parameters such as pulmonary function, degree of neuromuscular impairment, daytime sleepiness, and fatigue. This will help assess the prevalence of DM1 patients requiring nocturnal ventilatory treatments. We studied a random sample of 40 unrelated patients and found that 22/40 patients had obstructive sleep apnoea. Of these 22 patients, five showed also periodic breathing and four showed sleep hypoventilation. Nine patients were put on nocturnal ventilation following clinical and instrumental evaluations. Our study reveals that obstructive sleep apnoea is very common in these patients, but cannot be predicted on the basis of clinical-neurological features and diurnal functional respiratory tests. Our data emphasize that a periodical evaluation by polysomnography should be mandatory to ascertain, and treat if necessary, the presence of obstructive sleep apnoea, periodic breathing or nocturnal hypoventilation.
  Neuromuscular Disorders 12/2011; 22(3):219-24. · 2.80 Impact Factor
• Article: Altered layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy.

  Laura Rossini, Ramona F Moroni, Laura Tassi, Akiya Watakabe, Tetsuo Yamamori, Roberto Spreafico, Rita Garbelli
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  ABSTRACT: Neuropathologic investigations frequently reveal the presence of architectural cortical dysplasia in patients with temporal lobe epilepsy (TLE), sometimes as an isolated finding but more commonly associated with hippocampal sclerosis (HS) and white matter abnormalities. The histologic pattern and the developmental origin of these alterations are not clear, and their diagnostic criteria are poorly defined. The aim of this study was to investigate the expression patterns of layer-specific genes in cortical specimens from patients with TLE presenting different subtypes of cortical malformations in order to elucidate the disorganization of the laminar architecture of such epileptogenic abnormalities and provide evidence to enable a more objective neuropathologic diagnosis. We analyzed the expression patterns of CUX2, RORBETA, ER81, NURR1, and CTGF genes, respectively specific markers of layers II-III, IV, V, VI, and VIb, in surgical samples by means of in situ hybridization and compared them with those observed in control cortices. The pathologic samples included typical architectural dysplasia (group 1); temporal lobe sclerosis, a variant of architectural dysplasia (group 2); and white matter heterotopic neuronal aggregates, namely small lentiform nodules (group 3). These abnormalities may have been associated or not with HS. All of the genes had a laminar expression pattern in normal cortices, whereas groups 1 and 2 showed alterations mainly involving layers V and VI, and highlighted by the altered distribution of ER81- and NURR1-positive cells. The expression of ER81 and NURR1 genes was different among the groups, and atypical coexpression of NURR1 and CUX2 mRNA was detected in the neurons making up the small lentiform nodules. These findings indicate that defects in cortical organization involving the deeper cortical neurons may be a common etiopathogenic mechanism in group 1 and 2 cortical dysplasia, whether isolated or associated with HS, and that developmental disorders may also be present in the white matter (group 3). They also provide evidence that the layer-specific genes can be usefully used to investigate the neuropathology of human cortical dysplasia.
  Epilepsia 08/2011; 52(10):1928-37. · 3.96 Impact Factor
• Article: Theory of mind in frontal and temporal lobe epilepsy: cognitive and neural aspects.

  Anna Rita Giovagnoli, Silvana Franceschetti, Fabiola Reati, Annalisa Parente, Carmelo Maccagnano, Flavio Villani, Roberto Spreafico
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  ABSTRACT: Theory of mind (ToM) is an important prerequisite to social behavior. This study evaluated ToM in patients with temporal (TLE) or frontal lobe epilepsy (FLE) aiming to determine the cognitive aspects, severity, and pathophysiologic mechanisms of ToM impairment in focal epilepsy. One hundred thirty-eight patients with TLE (n = 109) or FLE (n = 29) and 69 healthy subjects underwent the Faux Pas task (FPT), which evaluates the recognition and comprehension of others' mental states, and neuropsychological tests for other cognitive functions. Factor analysis of all test scores yielded two ToM factors (Recognizing faux pas, FP; Excluding nonexistent FP) distinct from the Control, Language, Matching, and Praxis factors. With respect to healthy subjects, both TLE and FLE patients showed correct exclusion of nonexistent FPs but significantly lower recognition and comprehension of real FPs. FLE patients were also impaired with respect to TLE patients. In the whole patient group, schooling and group membership predicted ToM impairment. In FLE patients, the comprehension of mental states was predicted by disease duration, whereas TLE patients' comprehension of affects and intentions was associated with early age of seizure onset and medial temporal lobe sclerosis (MTLS). Focal epilepsy impairs advanced ToM abilities. FLE may affect online performances owing to long-lasting dysfunctions of the prefrontal areas. MTLS may provoke selective ToM deficits due to medial temporal damage, prefrontal dysfunctions, or early interference with cognitive development. Future studies are needed to determine the implications of ToM impairment on behavior and quality of life.
  Epilepsia 08/2011; 52(11):1995-2002. · 3.96 Impact Factor
• Article: Tractographic reconstruction protocol optimization in the rat brain in-vivo: towards a normal atlas.

  Maria Giulia Preti, Alessandro Di Marzio, Alfonso Mastropietro, Domenico Aquino, Giuseppe Baselli, Maria Marcella Laganà, Ileana Zucca, Carolina Frassoni, Roberto Spreafico
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  ABSTRACT: The tractographic reconstruction of anatomical and microstructural features provided by Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) gives essential information of brain damage in several pathological animal models. The optimization of a tractographic protocol is undertaken in normal rats for the future construction of a reference atlas, as prerequisite for preclinical pathological in-vivo studies. High field, preclinical in-vivo DTI faces important difficulties relevant to Signal-to-Noise Ratio (SNR), distortion, high required resolution, movement sensitivity. Given a pixel-size of 0.17 mm and TE/TR = 29/6500 ms, b value and slice thickness were fixed at 700 s/mm(2) and 0.58 mm, respectively, on preventive ex-vivo studies. In-vivo studies led to the choice of 30 diffusion directions, averaged on 16 runs. The final protocol required 51 min scanning and permitted a reliable reconstruction of main rat brain bundles. Tract reconstruction stopping rules required proper setting. In conclusion, the viability of DTI tractography on in-vivo rat studies was shown, towards the construction of a normal reference atlas.
  Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:8467-70.
• Article: Reelin and human nodular heterotopia.

  Maria Thom, Rita Garbelli, Roberto Spreafico
  Epilepsia 03/2011; 52(3):650-2. · 3.96 Impact Factor
• Source

  Available from: Ingmar Blümcke

  Article: An international consensus classification for focal cortical dysplasias.

  Ingmar Blümcke, Roberto Spreafico
  The Lancet Neurology 01/2011; 10(1):26-7. · 23.46 Impact Factor
• Source

  Available from: Ingmar Blümcke

  Article: The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission.

  Ingmar Blümcke, Maria Thom, Eleonora Aronica, Dawna D Armstrong, Harry V Vinters, Andre Palmini, Thomas S Jacques, Giuliano Avanzini, A James Barkovich, Giorgio Battaglia, [......], Imad Najm, Ciğdem Ozkara, Charles Raybaud, Alfonso Represa, Steven N Roper, Noriko Salamon, Andreas Schulze-Bonhage, Laura Tassi, Annamaria Vezzani, Roberto Spreafico
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  ABSTRACT:   Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. Thirty-two Task Force members have reevaluated available data on electroclinical presentation, imaging, neuropathological examination of surgical specimens as well as postsurgical outcome. The ILAE Task Force proposes a three-tiered classification system. FCD Type I refers to isolated lesions, which present either as radial (FCD Type Ia) or tangential (FCD Type Ib) dyslamination of the neocortex, microscopically identified in one or multiple lobes. FCD Type II is an isolated lesion characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). Hence, the major change since a prior classification represents the introduction of FCD Type III, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with epileptogenic lesions acquired in early life (i.e., traumatic injury, ischemic injury or encephalitis). This three-tiered classification system will be an important basis to evaluate imaging, electroclinical features, and postsurgical seizure control as well as to explore underlying molecular pathomechanisms in FCD.
  Epilepsia 01/2011; 52(1):158-74. · 3.96 Impact Factor
• Article: Accuracy of pre-surgical fMRI confirmed by subsequent crossed aphasia.

  Paolo Vitali, Nina Dronkers, Alexander Pincherle, Anna Rita Giovagnoli, Carlo Marras, Ludovico D'Incerti, Francesco Ghielmetti, Roberto Spreafico, Flavio Villani
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  ABSTRACT: Atypical patterns of language activation in functional MRI (fMRI) are not unusual, particularly in patients with severe epilepsy. Still, the functional significance of these activations is under debate. We describe a case of a right-handed patient affected by drug-refractory right temporal lobe epilepsy in whom pre-surgical fMRI showed bilateral language activations, greater in the right hemisphere (RH). After surgery, a right subdural hematoma caused epileptic status and severe aphasia. This post-surgical complication of a crossed aphasia confirmed the prior fMRI findings of RH language thus stressing the value of pre-surgical fMRI evaluations, even when surgery is planned in the RH of a right-handed patient.
  Neurological Sciences 11/2010; 32(1):175-80. · 1.32 Impact Factor
• Source

  Available from: Carolina Frassoni

  Article: Aquaporin 4 expression in control and epileptic human cerebral cortex.

  Valentina Medici, Carolina Frassoni, Laura Tassi, Roberto Spreafico, Rita Garbelli
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  ABSTRACT: Aquaporin-4 (AQP4), the prominent water channel in the brain, is particularly concentrated in astrocytic endfeet membranes lining the capillaries and the pia. This localisation pattern makes it well suited to regulate the flow of water and the homeostasis of the interstitial fluid surrounding the neurons. Using immunocytochemical and Western blot techniques, we investigated the expression of AQP4 and some related proteins (i.e. glial fibrillary acidic protein, glial glutamate transporter 1, the endothelial marker CD34, and dystrophin) in tissue taken from epileptic patients. To this end, we used surgical samples containing focal cortical dysplasia (FCD) Type IIB, samples of normal-appearing (cryptogenic) cortex, and samples from non-epileptic patients as controls. AQP4 expression and distribution in the cryptogenic patients were similar to those observed in the control cases, mainly concentrated around blood vessels. In the patients with FCD type IIB, severe malformation in cortical development, the protein was more expressed and the distribution pattern of AQP4 immunoreactivity was different, being strong in the neuropil and around several dysplastic neurons, whereas the vessels appeared to be less intensely stained by AQP4 and dystrophin. As the efficiency of AQP4 in regulating water and ion homeostasis in extracellular space depends on its spatial distribution in astrocytes, the different distribution of AQP4 protein in the FCD type IIB samples may modify fluid homeostasis control and the regular functioning of neuronal cells.
  Brain research 10/2010; 1367:330-9. · 2.46 Impact Factor
• Article: Type I focal cortical dysplasia: surgical outcome is related to histopathology.

  Laura Tassi, Rita Garbelli, Nadia Colombo, Manuela Bramerio, Giorgio Lo Russo, Francesco Deleo, Gloria Milesi, Roberto Spreafico
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  ABSTRACT: Pre-surgical and post-surgical data were examined and compared from 215 consecutive patients undergoing surgery for intractable epilepsy. Patients were selected on the basis of a proven histopathological diagnosis of type I focal cortical dysplasia (FCD I), alone or associated with other lesions. The patients were divided into five sub-groups: i) 66 with isolated FCD I, ii) 76 with FCD I and hippocampal sclerosis, iii) 49 with FCD I and tumours, iv) 16 with FCD I and other malformations of cortical development and v) eight with FCD I and anoxic-ischaemic or inflammatory diseases. The duration of epilepsy was greatest in patients with FCD I associated with hippocampal sclerosis, and those with isolated FCD I showed the highest seizure frequency at the time of surgery. Hippocampal sclerosis and tumours were the most frequent pathological lesions associated with FCD I in temporal lobe epilepsy. Febrile seizures significantly correlated with the presence of hippocampal sclerosis and FCD I. Isolated FCD I was observed in 31% of the patients, characterized by frequent seizures, negative magnetic resonance imaging, and frequent frontal or multilobar involvement. In comparison to patients with FCD I associated with hippocampal sclerosis, MCD or tumours, the patients with isolated FCD I had a worse post-surgical outcome (46% in class I). Our findings indicate that there is a high incidence of FCD I associated with other apparently distinct pathologies, particularly those affecting the temporal lobe, and highlight the need for a comprehensive clinicopathological approach for the classification of FCD I.
  Epileptic disorders: international epilepsy journal with videotape 09/2010; 12(3):181-91. · 1.50 Impact Factor