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Background and Objective: Tuberous Sclerosis Complex (TSC) is a rare systemic disease with a high prevalence of sleep disorders (SD), although they are still largely under-recognized. The objective of this study was to assess the prevalence of SD in adult patients with TSC, and to evaluate the relationship between sleep, epilepsy, and TSC associated neuropsychiatric disorders (TAND)., Materials and Methods: We administered Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) to 114 adult patients referring to different Italian centers. We also collected information on epilepsy and TAND., Results: PSQI, ISI, and ESS revealed a positive score, respectively, in 52 (46.0%), 30 (26.5%), and 16 (14.1%) patients. PSQI was positive in 26.7% of seizure free patients versus 61.9% with active epilepsy (p = 0.003), and the association remained significative applying a multivariate logistic model considering age, antiseizure medications, TAND and nocturnal epileptic seizures (p = 0.02). ISI was positive in 3.3% of seizure free patients versus 41.3% with active epilepsy (p = 0.0004). Applying a multivariate logistic model with the independent variables listed above, the association remained significant (p = 0.007). On the other hand, multivariate logistic model considering active epilepsy as an independent variable, revealed that TAND didn't appear a significant risk factor for positive PSQI (p = 0.43) nor ISI (p = 0.09)., Conclusions: Our results confirmed that SD are highly prevalent in adults with TSC, with active epilepsy acting as a significant risk factor. A careful assessment of sleep, above all in epileptic patients, is of crucial importance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: To evaluate the efficacy and safety of hypofractionated radiation therapy (HFRT) of the breast/chest wall and regional nodes in patients with locally advanced breast cancer and positive lymph nodes., Materials and Methods: One hundred and twenty-two patients treated between October 2016 and March 2020 with HFRT were retrospectively reviewed. A total dose of 42.4 Gy was delivered to the chest wall and lymph nodes in 16 fractions of 2.65 Gy each, using the IMRT technique. Patients treated with breast-conserving surgery received an overdose (concomitant boost of 3 Gy daily) with the SIB (Simultaneous Integrated Boost) technique., Results: Median age at diagnosis was 58 years (range 34-86 years) and median follow-up was 22 months (range 6-48 months). Overall survival (OS) at 1, 2 and 3 years was 100%, 97.3% and 90%, respectively. Disease-free survival (DFS) at 1, 2, and 3 years was 91.4%, 87%, and 84.8%, respectively. Distant metastasis-free survival (MFS) at 1, 2 and 3 years was 93.1%, 88% and 85.7%, respectively. Two patients (1.6%) experienced local recurrence on the chest wall during FUP. Twenty-one patients (17%) showed a grade 2 dermal toxicity, no grade 3 acute skin toxicity was found. Sixteen patients (13%) showed early-stage arm lymphedema (grade ≤ 2). Twenty-three patients (19%) showed a grade 2 late skin toxicity. Twenty patients (16%) had grade ≤ 2 late arm lymphedema., Conclusion: Given the excellent local control, survival rates and the low toxicity profile demonstrated, HFRT could be considered a valid therapeutic option in patients with locally advanced breast cancer., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS solid malign tumors. The effects on the CNS are disabling and often permanent with limited treatments, thus it is important that clinicians recognize the effects of cancer therapy on the CNS. Knowledge of these conditions can help the practitioner be more vigilant for signs and symptoms of potential neurological complications during the management of pediatric cancers. As early detection and more effective anticancer therapies extend the survival of cancer patients, treatment-related CNS toxicity becomes increasingly vital. This review highlights major neurotoxicities due to pediatric cancer treatments and new therapeutic strategies; CNS primary tumors, the most frequent solid tumors in childhood, are excluded because of their intrinsic neurological morbidity.

Purpose of Review: To analyze systematically the evidence currently available from the literature regarding the diagnosis, clinical characteristics, treatment and outcome of new daily persistent headache (NDPH)., Recent Findings: NDPH is a primary headache characterized by an abrupt onset with continuous daily pain that can persist for many months. Although self-limiting forms have been described, NDPH is frequently associated with high disability even in children and adolescents. For this reason, it is very important to recognize it from a diagnostic point of view and to treat it. We found little specific data on NDPH in developmental age. Most of the therapy studies have been conducted on adults with conflicting data. Currently, pediatric NDPH therapy is based on experiences in adult patients and in individuals with other forms of primary chronic headache, hence the need for more pediatric studies to fill this information gap., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The objective of this study is to present the rare case of a young girl with idiopathic intracranial hypertension secondary to hypoparathyroidism. Background: Idiopathic intracranial hypertension is a neurological syndrome characterized by elevated intracranial pressure (> 25 cmH 2 O) in the absence of intracerebral abnormalities or hydrocephalus. The pathophysiology of idiopathic intracranial hypertension is unknown, and rare cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. It is supposed that hypocalcemia causes decrease in the absorption of cerebrospinal fluid in arachnoidal granulations. Methods: The workup of the girl with idiopathic intracranial hypertension and hypoparathyroidism included physical examination, blood tests, diagnostic imaging, and lumbar puncture. Results: We present a 9-year-old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent an ophthalmologic examination that revealed papilledema. Lumbar puncture revealed an opening pressure of 65 cm H 2 O; cerebrospinal fluid analysis and brain computed tomography scan were normal. The patient started taking acetazolamide. Blood tests revealed hypocalcemia associated with high phosphorus level and undetectable PTH hormone, which led us to suspect hypoparathyroidism. She had never had cramps, paraesthesias, or tetany. Chvostek's and Trousseau's signs were positive. In the neck ultrasonography, parathyroids were not visible. Oral supplementation with calcitriol and calcium was started. Headache, nausea, and vomiting immediately disappeared after the lumbar puncture, and the papilledema improved gradually. Conclusions: Several anecdotal cases of idiopathic intracranial hypertension secondary to hypoparathyroidism have been described. However, our case report is of particular interest, since the child did not present with typical neurological hypoparathyroidism symptoms. Therefore, we recommend that hypoparathyroidism should be included in diagnostic investigations on children with clinical findings of idiopathic intracranial hypertension, because clinical manifestations of hypoparathyroidism are variable and may involve almost all organ systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sforza, Deodati, Moavero, Papetti, Frattale, Vigevano, Cianfarani and Valeriani.)

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray matter. The aquaporin-4 antibody (AQP4-IgG) is specific for NMOSD. Recently, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been found in a group of AQP4-IgG negative patients. NMOSD is rare among children and adolescents, but early diagnosis is important to start adequate therapy. In this report, we present cases of seven pediatric patients with NMOSD and we review the clinical and neuroimaging characteristics, diagnosis, and treatment of NMOSD in children.

Sleep disorders and primary headaches are frequent health problems in childhood, and they are often comorbid in an individual, linked by a mutual and complex relationship. This comorbidity is frequent and well-documented, but the available literature is usually biased in favor of one aspect or another, mainly depending on the expertise of the authors. The aim of this paper is to review existing literature on the diagnostic assessment of comorbid primary headaches and sleep disorders, so as to propose practical suggestions to accurately investigate the presence of comorbid conditions in children evaluated for primary headaches or for sleep disorders.

Migraine is the first in order of frequency of the neurological disorders, affecting both adult and paediatric populations. It is also the first cause of primary headaches in children. Migraine equivalents are periodic disorders that can be associated with migraine or considered as prognostic features of a future migraine manifestation. Despite the mechanisms underlying migraine and its equivalents are not entirely clear, several elements support the hypothesis of common pathophysiological patterns shared by these conditions. The aim of this review is thus to analyze the literature in order to highlight which currently known mechanisms may be common between migraine and its equivalents.

High Intellectual Potential (HIP) and High Functioning Autism (HFA) are two different conditions sharing some clinical and neurobiological features. The aim of the present study was to characterize a sample of HIP children (n: 16; M/F: 14/2; median age: 10 years) in comparison to those with HFA (n: 17; M/F: 16/1; median age: 13 years) and to neurotypically developed (NTD) children (n: 10; M/F: 4/6; median age: 11 years) from a clinical and neurophysiological perspective. Specifically, a standardized clinical assessment of cognitive and adaptive skills, autistic symptoms, executive functions and behavioral features was performed. Moreover, event-related potentials (ERPs) were recorded, referring specifically to the mismatch negativity (MMN) and P300 paradigm. Our data highlighted the presence of similarities between the intellectually gifted individuals and the ones with autism (i.e., a nonhomogeneous intellective profile, an adaptive skills impairment, subthreshold autistic symptoms and increased perfectionism). Interestingly, a distinct neurophysiological characterization between groups came out, with evidence of a reduced MMN amplitude only in the HFA group. Furthermore, no differences within groups in the P300 component emerged. Therefore, our results start to provide a more informative characterization of the HIP phenotype in comparison to those of HFA and NTD, highlighting the potential role of the MMN amplitude index in helping clinicians and researchers to distinguish between HIP and HFA. Nevertheless, further research on the topic is strongly needed.

Objectives: Although somatosensory evoked potentials (SEPs) after median nerve stimulation are widely used in clinical practice, the dorsal horn generator of the N13 SEP spinal component is not clearly understood. To verify whether wide dynamic range neurons in the dorsal horn of the spinal cord are involved in the generation of the N13 SEP, we tested the effect of heterotopic noxious conditioning stimulation, which modulates wide dynamic range neurons, on N13 SEP in healthy humans., Methods: In 12 healthy subjects, we performed the cold pressor test on the left foot as a heterotopic noxious conditioning stimulus to modulate wide dynamic range neurons. To verify the effectiveness of heterotopic noxious conditioning stimulation, we tested the pressure pain threshold at the thenar muscles of the right hand and recorded SEPs after right median nerve stimulation before, during and after the cold pressor test., Results: The cold pressor test increased pressure pain threshold by 15% (p = 0.04). During the cold pressor test, the amplitude of the N13 component was significantly lower than that recorded at baseline (by 25%, p = 0.04)., Discussion: In this neurophysiological study in healthy humans, we showed that a heterotopic noxious conditioning stimulus significantly reduced N13 SEP amplitude. This finding suggests that the N13 SEP might be generated by the segmental postsynaptic response of dorsal horn wide dynamic range neurons., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding this work, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [777,500]. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The statements and opinions presented here reflect the author's view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained therein. www.imi-paincare.eu; www.imi.europa.eu, (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction/aims: Spinal muscular atrophy type 1 (SMA 1) is a devastating motor neuron disorder that leads to progressive muscle weakness, respiratory failure and premature death. Although sensory electrophysiological changes have been anecdotally found in pediatric SMA 1 patients, the age of onset of sensory neuropathy remains unknown., Methods: Sensory nerve conduction studies of the median and sural nerves were performed in 28 consecutive SMA 1 patients of different ages. Sensory nerve conduction velocities and sensory nerve action potential (SNAP) amplitudes recorded in these patients were compared with those obtained from 93 healthy subjects stratified by age., Results: SNAP amplitudes decreased with increasing age in the sural and median nerves, without any significant difference between upper and lower limbs., Discussion: Our data suggest that sural and median nerve SNAP amplitudes are normal in younger patients, while an axonal neuropathy appears in older ones., (© 2021 Wiley Periodicals LLC.)

Anti- N -methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune illness characterized by a constellation of often severe, but treatable, psychiatric and neurological symptoms. Whereas symptoms such as psychosis and bizarre and abnormal motor behavior are common in adults, pediatric patients typically present with behavioral changes, irritability and sleep dysfunction. The recovery phase is usually slow and may be associated with longstanding adaptive, behavioral and neuropsychological problems. Very few studies explored the cognitive and adaptive sequelae in children with anti-NMDAR encephalitis. The present review article suggests that, although most children and adolescents return to their daily life and previous activities, they may have a low quality of life and show neuropsychological sequelae involving language, memory, especially verbal memory, and attentional resources, even after several months from the hospital discharge. In particular, the available results reveal difficulties in cognitive skills involving executive functions. This impairment is considered the "core" of the cognitive profile of young patients with anti-NMDAR encephalitis. On the other hand, some cognitive skills, such as general intelligence, show good overall recovery over time. Additional neuropsychological research evaluating larger samples, more homogenous methods and longitudinal studies is required.

Objectives: To investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents., Methods: SEPs were recorded in 6 patients suffering from Parkinson's disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed., Results: After median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts., Conclusions: Stimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential., Significance: Our results shed light on the subcortical processing of the somatosensory input of different modalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Multifocal motor neuropathy (MMN) is a slowly progressive motor neuropathy characterized by asymmetric muscle weakness without sensory involvement. Typically, MMN respond completely to treatment with intravenous immunoglobulin (IVIg). MMN is even rarer in the pediatric population, where only five patients have been reported up to now., Case Report: We discuss the 3-year follow-up of a 13-year-old girl with MMN who was positive for IgM antibodies to gangliosides GM1. She was diagnosed with MMN in accordance with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria. Serological studies revealed that she tested positive for IgM antibodies to GM1. She underwent intravenous methylprednisolone followed by an oral prednisone taper, intravenous immunoglobulin (IVIg), plasma exchange followed by IVIG and prednisone and Rituximab. No improvement was referred. At the present, she shows flaccid tetraplegia, facial diplegia, and bulbar cranial nerve palsy., Conclusion: Although childhood onset MMN is rare, most patients reported in literature respond to IVIg treatment. In a few cases, however, IVIg can be ineffective. In our patient, IVIg as well as treatment with prednisolone, plasma exchange and rituximab have failed., Competing Interests: None declared., (Thieme. All rights reserved.)

Background/aim: We evaluated local control and toxicity in patients receiving radiotherapy associated with immune check point inhibitors and analyzed which oligometastatic disease setting benefits the most from local ablation in terms of advantage in overall survival., Patients and Methods: We retrospectively identified 60 oligoprogressive patients treated with a PD-1 inhibitor in association with radiotherapy on the site of progression (119 lesions)., Results: After a median follow-up of 11.7 months (range=1-39 months), we observed complete response (CR) in 45/119, partial response (RP) in 42/119, and stable disease (SD) in 30/119 patients. Nine radionecrotic events occurred. Two patients experienced grade 3 toxicities and 32 patients reported grade 2 toxicities. The number of radiologically evident metastatic organs in patients who received concomitant PD-1 inhibitors and radiotherapy showed a significant increase in survival (respectively, 73% after 12 months and 47% after 24 months) in patients with 0-3 metastatic organs compared to those with more than 3 organ sites involved (p<0.0001)., Conclusion: Radiotherapy associated with PD-1 inhibitors is overall safe and efficacious. Patients eligible for intensification of local treatments should have less or equal to 3 metastatic organ sites., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To investigate whether radiotherapy as metastasis-directed therapy (MDT) on oligo-progressive sites in metastatic castration-resistant prostate cancer (mCRPC) patients during treatment with androgen receptor-targeted therapy (ARTT) may lead to control resistant lesions, prolonging ARTT. We analysed progression free survival, overall survival and prognostic parameters that can identify patients that best suit to this approach., Patients and Methods: Retrospective analysis of a total of 67 lesions in 42 mCRPC patients treated with ablative or palliative RT to oligoprogressive lesions during ARTT. Twenty-eight patients (67%) underwent ARTT with Abiraterone acetate and 14 patients (33%) underwent ARTT with Enzalutamide. Median time between the start of ADT and ARTT beginning was 50.14 months (range 3.37-219 months). We treated 58 lesions (87%) with 3D conformal radiotherapy (3DCRT) and nine lesions (13%) with stereotactic body radiotherapy (SBRT). The Kaplan Meier method was used to assess the median overall survival (OS) and the progression-free survival (PFS)., Results: Median follow-up was 28 months (range 3-82 months). Median OS was 32.5 months (95% CI 25.77-39.16), 1 and 2-year OS were 71.6% and 64.1%, respectively. Median PFS was 19,8 months (95% CI 11.34-28.31), 1 and 2-year PFS were 67.2% and 47.4%, respectively. Median OS for patients that underwent radiotherapy before 6 months from the start of ARTT was 23.4 months (95% CI 2.04-44.89) and 45.5 months (95% CI 31.19-59.8) for patients that underwent radiotherapy after 6 months ( p = 0.009 )., Conclusion: Local ablative radiation therapy directed to progressive metastasis is a non-invasive, well tolerated treatment with efficacy on prolonging clinical benefit of systemic therapies with ARTT. Patients who underwent RT >6 months from the start of ARTT presented a statistically better OS and PFS compared with patients who underwent radiotherapy <6 months from the start of ARTT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Massaro, Facondo, Vullo, Aschelter, Rossi, De Sanctis, Marchetti, Osti and Valeriani.)

Migraine and tension-type headache are common in children and adolescents, but several other headache disorders may pose a great challenge in diagnosis and management to families and attending clinicians. In this review, we highlight several of these disorders, which need appropriate assessment to make the right diagnosis and appropriate investigations where necessary. Timely recognition and implementation of appropriate management strategies can improve the health of children with some disorders, and is vital in achieving improvement in the quality of life.

There is a high comorbidity between migraine and sleep disorders (SD), with a mutual dependence between sleep and headache. This study aimed to analyze the relationship between headache features (migraine frequency and severity, migraine equivalents, use and efficacy of treatments) and sleep in pediatric migraine. Parents of children and adolescents with migraine completed the Children's Sleep Habits Questionnaire (CSHQ) and the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) and answered questions about headache characteristics. The presence of SD was defined according to CSHQ score. SD were detected in 72.9% of 140 subjects, but only 5.0% already received a diagnosis. Patients with SD presented statistically significant higher headache frequency ( p = 0.031) and higher prevalence of migraine equivalents ( p = 0.007). A higher CSHQ total score was associated with higher frequency of severe attacks ( p = 0.012) and lower acute drug efficacy ( p = 0.003). Significant positive correlations of sleep onset delay, sleep duration and nightwakings subscales with migraine frequency emerged. Our findings indicate that SD are highly prevalent in pediatric migraine and frequently associated with a higher headache severity and lower response to acute therapy, but often remain underdiagnosed. Improving sleep quality could help to reduce migraine intensity and disability and vice versa.

The link between migraine and nutrition can be explored from several points of view. Lifestyle and, in particular, aspects of nutrition can have a significant impact on the course of pediatric migraine. In addition, some dietary treatments, such as the ketogenic diet, and some active ingredients present in foods (nutraceuticals) may have a therapeutic effect on migraine. A diet that can control weight gain and obesity has beneficial effects on migraine severity. On the other hand, when we talk about the link between nutrition and headaches, it is also necessary to point out that some public information is actually fake news that has no scientific basis. The purpose of this review is to provide an update on the salient points linking pediatric migraine to nutritional principles, focusing on the relationship between weight and headaches, the therapeutic effect of food for medical purposes, the ketogenic diet as a migraine treatment, and the relationship between migraine and dietary habits.

Background: Metastatic castration-resistant prostate cancer (mCRPC) is the final stage of pCa history and represents a clinically relevant phenotype with an elevated burden of mortality. The aim of the present study was to evaluate the efficacy and safety of enzalutamide in a "real-life" setting in mCRPC patients., Methods: Data about all mCRPC patients treated with enzalutamide from September 2017 to September 2018 were collected. Demographics, comorbidities, clinical parameters, outcomes, toxicity, overall survival and progression free survival were analyzed., Results: Overall, 158 patients were enrolled. Mean age was 75.8 (±8.7) years with a baseline median PSA of 16.5 (IQR 7.4-47.8) ng/mL. The median follow-up lasted 7.7 (IQR 4-14.1) months. Of all the 10.1% of patients reported grade 3-4 adverse events. 43.7% of patients experienced a progression. Overall, the 6 and 12 months PFS rates were 69.5% (95% CI: 61.7-78.3%) and the 45.6% (95% CI: 36.5-57.1%); a median baseline PSA>16 ng/mL (HR:2.0, 95% CI: 1.2-3.3, P<0.005), the use of opioid (HR: 3.1, 95% CI: 1.9-5.0, P<0.001), a previous treatment (abiraterone, docetaxel or abiraterone + docetaxel) were significantly associated with higher rates of cancer progression. Conversely, a brief pain questionnaire of 0-1 (HR: 0.4, 95% CI: 0.2-0.7, P<0.001), a 12 weeks 50% PSA reduction (HR: 0.4, 95% CI: 0.2-0.8, P<0.006) and a longer time to mCRPC (HR: 0.4, 95% CI: 0.3-0.7, P<0.002) were related to lower cancer progression rates., Conclusions: Our data shows an effective and safe profile of enzalutamide in a "real world" perspective in patients with mcRPC.

Background: Migraine is the most common neurological disease, with high social-economical burden. Although there is growing evidence of brain structural and functional abnormalities in patients with migraine, few studies have been conducted on children and no studies investigating cortical gyrification have been conducted on pediatric patients affected by migraine without aura., Methods: Seventy-two pediatric patients affected by migraine without aura and eighty-two controls aged between 6 and 18 were retrospectively recruited with the following inclusion criteria: MRI exam showing no morphological or signal abnormalities, no systemic comorbidities, no abnormal neurological examination. Cortical thickness (CT) and local gyrification index (LGI) were obtained through a dedicated algorithm, consisting of a combination of voxel-based and surface-based morphometric techniques. The statistical analysis was performed separately on CT and LGI between: patients and controls; subgroups of controls and subgroups of patients., Results: Patients showed a decreased LGI in the left superior parietal lobule and in the supramarginal gyrus, compared to controls. Female patients presented a decreased LGI in the right superior, middle and transverse temporal gyri, right postcentral gyrus and supramarginal gyrus compared to male patients. Compared to migraine patients younger than 12 years, the ≥ 12-year-old subjects showed a decreased CT in the superior and middle frontal gyri, pre- and post-central cortex, paracentral lobule, superior and transverse temporal gyri, supramarginal gyrus and posterior insula. Migraine patients experiencing nausea and/or vomiting during headache attacks presented an increased CT in the pars opercularis of the left inferior frontal gyrus., Conclusions: Differences in CT and LGI in patients affected by migraine without aura may suggest the presence of congenital and acquired abnormalities in migraine and that migraine might represent a vast spectrum of different entities. In particular, ≥ 12-year-old pediatric patients showed a decreased CT in areas related to the executive function and nociceptive networks compared to younger patients, while female patients compared to males showed a decreased CT of the auditory cortex compared to males. Therefore, early and tailored therapies are paramount to obtain migraine control, prevent cerebral reduction of cortical thickness and preserve executive function and nociception networks to ensure a high quality of life., (© 2021. The Author(s).)

Peripheral neuropathy is a well described complication in children with cancer. Oncologists are generally well aware of the toxicity of the main agents, but fear the side effects of new drugs. As chemotherapeutic agents have been correlated with the activation of the immune system such as in Chemotherapy Induced Peripheral Neuropathy (CIPN), an abnormal response can lead to Autoimmune Peripheral Neuropathy (APN). Although less frequent but more severe, Radiation Induced Peripheral Neuropathy may be related to irreversible peripheral nervous system (PNS). Pediatric cancer patients also have a higher risk of entering a Pediatric Intensive Care Unit for complications related to therapy and disease. Injury to peripheral nerves is cumulative, and frequently, the additional stress of a malignancy and its therapy can unmask a subclinical neuropathy. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication along with patient factors, namely age and inherited susceptibilities. The recent identification of individual genetic variations has advanced the understanding of physiopathological mechanisms and may direct future treatment approaches. More research is needed on pharmacological agents for the prevention or treatment of the condition as well as rehabilitation interventions, in order to allow for the simultaneous delivery of optimal cancer therapy and the mitigation of toxicity associated with pain and functional impairment. The aim of this paper is to review literature data regarding PNS complications in non-primary pediatric cancer.