Roberta Di Giacomo - Academia.edu (original) (raw)

Papers by Roberta Di Giacomo

Clinical neurophysiology, Jul 1, 2024

medRxiv (Cold Spring Harbor Laboratory), Jan 26, 2024

Neural Computing and Applications

A light microscopy-based histopathology diagnosis of human brain specimens obtained from epilepsy... more A light microscopy-based histopathology diagnosis of human brain specimens obtained from epilepsy surgery remains the gold standard to confirm the underlying cause of a patient’s focal epilepsy and further inform postsurgical patient management. The differential diagnosis of neocortical specimens in the realm of epilepsy surgery remains, however, challenging. Herein, we developed an open access, deep learning-based classifier to histopathologically assess whole slide microscopy images (WSI) and to automatically recognize various subtypes of Focal Cortical Dysplasia (FCD), according to the ILAE consensus classification update of 2022. We trained a convolutional neuronal network (CNN) with fully digitalized WSI of hematoxylin–eosin stainings obtained from 125 patients covering the spectrum of mild malformation of cortical development (mMCD), mMCD with oligodendroglial hyperplasia in epilepsy (MOGHE), FCD ILAE Type 1a, 2a and 2b using 414 formalin-fixed and paraffin-embedded archival t...

Aging Clinical and Experimental Research, 2013

Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/inc... more Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

Journal of Neurology, Neurosurgery, and Psychiatry, Apr 11, 2016

Brain Pathology, Dec 23, 2022

Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previo... more Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previously demonstrated a severe spine loss and synaptic reorganization in human neocortices presenting Type II focal cortical dysplasia (FCD), a developmental malformation and frequent cause of drug‐resistant focal epilepsy. We extend the findings, investigating the potential role of complement components C1q and C3 in synaptic pruning imbalance. Data from Type II FCD were compared with those obtained in focal epilepsies with different etiologies. Neocortical tissues were collected from 20 subjects, mainly adults with a mean age at surgery of 31 years, admitted to epilepsy surgery with a neuropathological diagnosis of: cryptogenic, temporal lobe epilepsy with hippocampal sclerosis, and Type IIa/b FCD. Dendritic spine density quantitation, evaluated in a previous paper using Golgi impregnation, was available in a subgroup. Immunohistochemistry, in situ hybridization, electron microscopy, and organotypic cultures were utilized to study complement/microglial activation patterns. FCD Type II samples presenting dendritic spine loss were characterized by an activation of the classical complement pathway and microglial reactivity. In the same samples, a close relationship between microglial cells and dendritic segments/synapses was found. These features were consistently observed in Type IIb FCD and in 1 of 3 Type IIa cases. In other patient groups and in perilesional areas outside the dysplasia, not presenting spine loss, these features were not observed. In vitro treatment with complement proteins of organotypic slices of cortical tissue with no sign of FCD induced a reduction in dendritic spine density. These data suggest that dysregulation of the complement system plays a role in microglia‐mediated spine loss. This mechanism, known to be involved in the removal of redundant synapses during development, is likely reactivated in Type II FCD, particularly in Type IIb; local treatment with anticomplement drugs could in principle modify the course of disease in these patients.

Epilepsy & Behavior, Nov 1, 2020

Abstract During epidemic outbreaks, epilepsy course can be modified by different physical and psy... more Abstract During epidemic outbreaks, epilepsy course can be modified by different physical and psychological stressors and, most importantly, by irregular therapy intake. The effect of COVID-19 and quarantine isolation on the course of epilepsy and on incidence of new-onset seizures is still unclear. With the aim of managing epilepsy in quarantined patients, three Italian Epilepsy Centers set up telephone consultations using a semistructured interview, allowing a prospective collection of data on seizure course and other seizure-related problems during pandemic. The collected data on seizure course were compared with the analogous period of 2019. The level of patients' concern relating to the COVID-19 pandemic was also assessed using a numeric rating scale. To address the effect of COVID-19 pandemic on seizure incidence, data collection included the number of consultations for first seizures, relapse seizures, and status epilepticus (SE) in the emergency department of one of the participating centers. Clinical telephone interviews suggest the absence of quarantine effect on epilepsy course in our cohort. No differences in incidence of emergency consultations for seizures over a two-month period were also observed compared with a control period. As demonstrated in other infective outbreaks, good antiepileptic drug (AED) supplying, precise information, and reassurance are the most important factors in chronic conditions to minimize psychological and physical stress, and to avoid unplanned treatment interruptions.

Neurological Sciences, Jul 17, 2023

World Neurosurgery, Mar 1, 2023

Epileptic Disorders, Apr 1, 2021

The study of dementia and epilepsy may provide particular insight into behavioural alterations. W... more The study of dementia and epilepsy may provide particular insight into behavioural alterations. We describe a rare case of ictal aggressive behaviour in a patient with focal epilepsy associated with a non‐dominant dorso‐lateral prefrontal lesion. During focal seizures, our patient showed intense agitation and anger, for a long time misinterpreted as psychogenic attacks, which disappeared after epilepsy surgery. The defined anatomical origin of such ictal emotional behaviour is not fully understood, however, the dorso‐lateral prefrontal area appears to correlate less frequently with aggressiveness compared to the antero‐mesial area. We describe the electroclinical data of our patient and provide a brief review of the mechanisms underlying aggressive conduct in epilepsy and dementia. An understanding of this mechanism could help to clarify the neural basis and treatment of violence associated with these and other neurological disorders. [Published with video sequence].

Clinical Neurophysiology, 2021

Journal of Neuroimmunology, Dec 1, 2019

We report the case of a 42-year-old woman who presented with vertigo and migraine and rapidly dev... more We report the case of a 42-year-old woman who presented with vertigo and migraine and rapidly developed cognitive decline and seizures. Both serum and cerebro-spinal fluid samples showed high titer of anti-glutamic acid decarboxylase (anti-GAD65) antibodies (998,881 IU/ml and 54,687 IU/ml respectively). Limbic encephalitis was diagnosed and high dose steroids treatment started. During one-year follow-up, without further immunomodulatory therapy, the patient became seizure free, and cognitive functions returned to normal. Serum anti-GAD65 antibodies titer decreased significantly but remained elevated (192,680 IU/ml). We discuss the prognostic and pathogenic value of high titer anti-GAD65 antibodies and its variations in a case of autoimmune limbic encephalitis.

Epilepsia, Dec 1, 2020

Objective: To assess seizure and cognitive outcomes and their predictors in children (<16 years a... more Objective: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. Methods: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons. Results: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short-vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. Significance: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.

Journal of Neurology, Apr 11, 2022

Cobalamin C (CblC) deficiency (alias methylmalonic aciduria and homocystinuria, CblC type, OMIM #... more Cobalamin C (CblC) deficiency (alias methylmalonic aciduria and homocystinuria, CblC type, OMIM # 277,400) is the most common inborn error of intracellular cobalamin metabolism. The onset is usually in the first year of life [1], but occasionally it can present in adolescence or adulthood with a large spectrum of neurological and extra-neurological features, including neuropsychiatric symptoms, myelopathy/ peripheral neuropathy, thromboembolism, and kidney disease [2, 3]. CblC deficiency can be a progressive and even life-threatening disease when not promptly recognized and treated [1]. With therapy, the prognosis can be good, especially in lateonset cases [4], while if treatment is delayed, neurological sequelae are usually permanent [1, 4]. In this article, we report a case of adult-onset CblC deficiency manifesting for years as an epileptic syndrome with myoclonus. A 36 year-old man, born to non-consanguineous parents and with normal psychomotor development, was referred to our Epilepsy Centre because of a complicated, drug-resistant epileptic syndrome with myoclonus. His medical history started at the age of 18 when he had one morpheic tonic–clonic seizure (TCS), followed by recurrent jerks involving both arms suggestive of myoclonic seizures (Fig 1a). Brain MRI was unremarkable, and interictal electroencephalography (EEG) showed normal background and few spikes. Juvenile myoclonic epilepsy (JME) was suspected, and valproate was started with benefit. At age 20, valproate was stopped with no further TCSs and only occasional jerks. At age 32, he had another TCS, and levetiracetam was initiated. At age 34, he developed renal failure with estimated glomerular filtration rate reduction until 32.7 ml/min/1.73 mq (normal value> 60); renal biopsy was non-specific.[5] At age 35, he developed cognitive decline with superimposed episodes of severe confusion, progressive memory deterioration, poor speech, and insomnia. He also presented behavioural changes with social withdrawal, anxiety, kinaesthetic hallucinations, and compulsive disorder. There was a concomitant marked worsening of the frequency and severity of jerks and seizure recurrence (Fig. 1a). Given the lack of response to anti-seizure medication, he was referred to our Institute. Our neurological examination revealed bradykinesia and motor awkwardness, subtle tremor-like finger twitches, and exaggerated deep tendon reflexes, whereas neuropsychological assessment revealed moderate multi-domain dysfunction (i.e., attention, naming, verbal fluency, figure recognition, learning, long-term visual memory, praxis, and theory of mind difficulties). Brain MRI showed diffuse atrophy without leukoencephalopathy, and brain FDG-PET revealed marked hypometabolism in multiple regions (Fig. 1b, c). Neuro-ophthalmologic evaluation showed optic nerve atrophy with retinopathy. Spinal cord MRI was normal, while motor-evoked potentials of lower limbs showed central conduction time increase. EEG and magnetoencephalography showed diffuse delta waves, and simultaneous electromyography recording during the maintenance of hand extension showed repeated myoclonic Roberta Di Giacomo and Ettore Salsano have contributed equally to the present work.

Clinical Neurophysiology, Dec 1, 2021

OBJECTIVE We use co-registration of foramen-ovale and scalp-EEG to investigate network alteration... more OBJECTIVE We use co-registration of foramen-ovale and scalp-EEG to investigate network alterations in temporal-lobe epilepsy during focal seizures without (aura) or with impairment of awareness (SIA). METHODS One aura and one SIA were selected from six patients. Temporal dynamic among 4 epochs, as well as the differences between aura and SIA, were analyzed through partial directed coherence and graph theory-based indices of centrality. RESULTS Regarding the auras temporal evolution, fronto-parietal (FP) regions showed decreased connectivity with respect to the interictal period, in both epileptogenic (EH) and non-epileptogenic hemisphere (nEH). During SIAs, temporal dynamic showed more changes than auras: centrality of mesial temporal (mT) regions changes during all conditions, and nEH FP centrality showed the same dynamic trend of the aura (decreased centrality), until the last epoch, close to the impaired awareness, when showed increased centrality. Comparing SIA with aura, in proximity of impaired awareness, increased centrality was found in all the regions, except in nEH mT. CONCLUSIONS Our findings suggested that the impairment of awareness is related to network alterations occurring first in neocortical regions and when awareness is still retained. SIGNIFICANCE The analysis of 'hub' alteration can represent a suitable biomarker for scalp EEG-based prediction of awareness impairment.