Diagnostic controversies in recurrent painful ophthalmoplegic neuropathy: single case report with a systematic review.

BACKGROUND: Ophthalmoplegic migraine, renamed "Recurrent Painful Ophthalmoplegic Neuropathy" (RPON) in 2013 by the International Headache Society is a rare neurologic disorder characterized by recurrent attacks of ophthalmoplegia associated to ipsilateral headache. The etiology is still unknown. Typical magnetic resonance imaging findings show a focal nerve thickening and contrast enhancement. In the majority of cases, there is a full recovery within days or weeks. There is no evidence supporting a specific treatment. The review defines the characteristics of the recurrent painful ophthalmoplegic neuropathy in patients within 2 years of age underlying the importance of the role of magnetic resonance imaging even in presence of the first attack. Thus, an emblematic case report is presented. CASE PRESENTATION: The authors present a case of third cranial nerve paresis in a 17-month-old male child, presenting a neuroradiological pattern highly suggestive of schwannoma, aneurism or recurrent painful ophthalmoplegic neuropathy. Thus, a review of the literature with the pediatric casuistry of recurrent painful ophthalmoplegic neuropathy occurred within 2 years of age focusing on diagnostic considerations is presented. The authors highlight the importance to consider recurrent painful ophthalmoplegic neuropathy in presence of magnetic resonance imaging findings and clinical symptoms referable to aneurysm or schwannoma. Thus, the review defines the characteristics and the neuroradiological findings at the first RPON attack occurred under 2 years of age. CONCLUSION: Although two attacks are necessary, the review strongly suggests to consider recurrent painful ophthalmoplegic neuropathy even at the first attack, in presence of described characteristics and the aforementioned magnetic resonance imaging findings.

Spinal cord compression as tumor onset: an unusual case report of Hodgkin lymphoma in a teenager.

BACKGROUND: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us. CASE PRESENTATION: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function. CONCLUSIONS: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management.

Ketogenic diet for infants with epilepsy: A literature review.

The ketogenic diet (KD) is an established, nonpharmacological treatment for drug-resistant epilepsy (DRE). Actually, KD and its variants have been shown to be elective and resolute for patients with glucose transporter type 1 (GLUT1) deficiency. The aim of this review was to study the use of KD and its variants in infancy, including the neonatal age, and demonstrate the safety and efficacy of this treatment in patients with the age of 0-23 months affected by DRE already subjected to pharmacological approach attempts. A literature search was conducted using PubMed as the medical database source. We used the age limit of 0-23 months, and we considered only articles published between the years 2015 and 2018, in light of increasing interest worldwide in the use of KD and its variants to manage DRE. We included 52 publications: 1 Cochrane study, 22 retrospective studies, 9 prospective studies, 4 randomized controlled trials (RCTs), 12 clinical cases, and 4 clinical reviews. Literature data showed that KD and its variants are safe and useful in patients with the age of 0-23 months with DRE. Classical KD is of first choice in the treatment of GLUT1 deficiency. Earlier introduction of KD in GLUT1 promises a better outcome and a decrease in seizure frequency in these patients.

Neurocutaneous melanocytosis (melanosis).

Neurocutaneous melanosis (NCM; MIM # 249400; ORPHA: 2481], first reported by the Bohemian pathologist Rokitansky in 1861, and now more precisely defined as neurocutaneous melanocytosis, is a rare, congenital syndrome characterised by the association of (1) congenital melanocytic nevi (CMN) of the skin with overlying hypertrichosis, presenting as (a) large (LCMN) or giant and/or multiple (MCMN) melanocytic lesions (or both; sometimes associated with smaller "satellite" nevi) or (b) as proliferative melanocytic nodules; and (2) melanocytosis (with infiltration) of the brain parenchyma and/or leptomeninges. CMN of the skin and leptomeningeal/nervous system infiltration are usually benign, more rarely may progress to melanoma or non-malignant melanosis of the brain. Approximately 12% of individuals with LCMN will develop NCM: wide extension and/or dorsal axial distribution of LCMN increases the risk of NCM. The CMN are recognised at birth and are distributed over the skin according to 6 or more patterns (6B patterns) in line with the archetypical patterns of distribution of mosaic skin disorders. Neurological manifestations can appear acutely in infancy, or more frequently later in childhood or adult life, and include signs/symptoms of intracranial hypertension, seizures/epilepsy, cranial nerve palsies, motor/sensory deficits, cognitive/behavioural abnormalities, sleep cycle anomalies, and eventually neurological deterioration. NMC patients may be symptomatic or asymptomatic, with or without evidence of the typical nervous system changes at MRI. Associated brain and spinal cord malformations include the Dandy-Walker malformation (DWM) complex, hemimegalencephaly, cortical dysplasia, arachnoid cysts, Chiari I and II malformations, syringomyelia, meningoceles, occult spinal dysraphism, and CNS lipoma/lipomatosis. There is no systemic involvement, or only rarely. Pathogenically, single postzygotic mutations in the NRAS (neuroblastoma RAS viral oncogene homologue; MIM # 164790; at 1p13.2) proto-oncogene explain the occurrence of single/multiple CMNs and melanocytic and non-melanocytic nervous system lesions in NCM: these disrupt the RAS/ERK/mTOR/PI3K/akt pathways. Diagnostic/surveillance work-ups require physical examination, ophthalmoscopy, brain/spinal cord magnetic resonance imaging (MRI) and angiography (MRA), positron emission tomography (PET), and video-EEG and IQ testing. Treatment strategies include laser therapy, chemical peeling, dermabrasion, and surgical removal/grafting for CMNs and shunt surgery and surgical removal/chemo/radiotherapy for CNS lesions. Biologically targeted therapies tailored (a) BRAF/MEK in NCM mice (MEK162) and GCMN (trametinib); (b) PI3K/mTOR (omipalisib/GSK2126458) in NMC cells; (c) RAS/MEK (vemurafenib and trametinib) in LCMNs cells; or created experimental NMC cells (YP-MEL).

Introduction to phacomatoses (neurocutaneous disorders) in childhood.

The Dutch ophthalmologist, Jan van der Hoeve, first introduced the terms phakoma/phakomata (from the old Greek word "ϕαχοσ" = lentil, spot, lens-shaped) to define similar retinal lesions recorded in tuberous sclerosis (1920) and in neurofibromatosis (1923). He later applied this concept: (a) to similar lesions in other organs (e.g. brain, heart and kidneys) (1932) and (b) to other disorders (i.e. von Hippel-Lindau disease and Sturge-Weber syndrome) (1933), and coined the term phakomatoses. At the same time, the American neurologist Paul Ivan Yakovlev and psychiatrist Riley H. Guthrie (1931) established the key role of nervous systems and skin manifestations in these conditions and proposed to name them neurocutaneous syndromes (or ectodermoses, to explain the pathogenesis). The Belgian pathologist, Ludo van Bogaert, came to similar conclusions (1935), but used the term neuro-ectodermal dysplasias. In the 1980s, the American paediatric neurologist Manuel R. Gomez introduced the concept of "hamartia/hamartoma" instead of phakoma/phakomata. "Genodermatoses" and "neurocristopathies" were alternative terms still used to define these conditions. Nowadays, however, the most acclaimed terms are "phacomatoses" and "neurocutaneous disorders", which are used interchangeably. Phacomatoses are a heterogeneous group of conditions (mainly) affecting the skin (with congenital pigmentary/vascular abnormalities and/or tumours), the central and peripheral nervous system (with congenital abnormalities and/or tumours) and the eye (with variable abnormalities). Manifestations may involve many other organs or systems including the heart, vessels, lungs, kidneys and bones. Pathogenically, they are explained by interplays between intra- and extra-neuronal signalling pathways encompassing receptor-to-protein and protein-to-protein cascades involving RAS, MAPK/MEK, ERK, mTOR, RHOA, PI3K/AKT, PTEN, GNAQ and GNA11 pathways, which shed light also to phenotypic variability and overlapping. We hereby review the history, classification, genomics, clinical manifestations, diagnostic criteria, surveillance protocols and therapies, in phacomatoses: (1) predisposing to development of tumours (i.e. the neurofibromatoses and allelic/similar disorders and schwannomatosis; tuberous sclerosis complex; Gorlin-Goltz and Lhermitte-Duclos-Cowden syndromes); (2) with vascular malformations (i.e. Sturge-Weber and Klippel-Trenaunay syndromes; megalencephaly/microcephaly-capillary malformation syndromes; CLOVES, Wyburn-Mason and mixed vascular nevus syndromes; blue rubber bleb nevus syndrome; hereditary haemorrhagic telangiectasia); (3) with vascular tumours (von Hippel-Lindau disease; PHACE(S)); (4) with pigmentary/connective tissue mosaicism (incontinentia pigmenti; pigmentary/Ito mosaicism; mTOR-related megalencephaly/focal cortical dysplasia/pigmentary mosaicism; RHOA-related ectodermal dysplasia; neurocutaneous melanocytosis; epidermal/papular spilus/Becker nevi syndromes; PENS and LEOPARD syndromes; encephalocraniocutaneous lipomatosis; lipoid proteinosis); (5) with dermal dysplasia (cerebellotrigeminal dermal dysplasia); and (6) with twin spotting or similar phenomena (phacomatosis pigmentovascularis and pigmentokeratotica; and cutis tricolor).

Apnea events in neonatal age: A case report and literature review.

BACKGROUND: Among the most common autonomic signs visible in preterm neonates, apnea can represent the first sign of several neurologic and non-neurologic disorders, and seizure is a relatively infrequent cause. Herein authors present a case of neonatal autonomic apnea, discussing the polygraphic video-EEG features of this pathological entity and the differential diagnosis with central apnea and autonomic apnea. CASE REPORT: A female preterm Caucasian infant (29 + 4 weeks' gestational age (GA)), first twin of a twin pregnancy, at birth was intubated and surfactant administration was performed. She was ventilated via invasive ventilation for three days, with subsequent weaning with non-invasive ventilation for other two days, when she stopped requiring any ventilator support. After one week the ventilation weaning, the child presented episodes of cyanosis associated with sudden oxygen desaturation, skin pallor, apnea, and bradycardia. Therefore, the child underwent a continuous video-eeg recording with polygraphic study. The exam showed the presence of apneic episodes with an abrupt and clear start, associated with oxygen desaturation at 70%, with minimal thoracic effort at onset, and then evolving into central apnea. Central apnea lasted about 16 s and presented clear start- and end-points. These episodes were also associated with suppression of the EEG trace in frequency and amplitude, and after about 10 s of central apnea an abrupt decrease of the child's heart rate (more than 50% variation, from 160 bpm to 65 bpm) was recorded. In the suspect of epileptic apneas of autonomic origin, a therapy with oral Levetiracetam, at a starting dose of 10 mg/Kg/day, then increased up to 40 mg/Kg/day, was initiated, and after about 48 h the first administration of the anticonvulsant therapy, no new episodes of cyanosis or electrical apneas were recorded. HYPOTHESIS: Herein the authors suggest to consider the diagnosis of autonomic seizures in those neonates with apneic events associated with EEG suppression. Considering that apnea events are not only present in preterm infants but also in term neonates, it is mandatory to diagnose in this context neonatal seizures for a correct diagnosis and a proper therapeutic choice.

Prevalence of high ankle-brachial index (ABI) in general population of Southern Italy, risk factor profiles and systemic cardiovascular co-morbidity: an epidemiological study.

Many studies have been carried out to assess the prevalence, risk factors and co-morbidities of peripheral artery disease (PAD). By contrast, to date there is a lack of data on patients with high-ABI. This study aimed at estimating the prevalence of increased ABI (ABI>1.4) and to evaluate the involvement of traditional cardiovascular (CV) risk factors and the atherosclerotic burden (peripheral and carotid arteries) of these patients in a population of Southern Italy. We invited 9647 subjects, age ranging from 30 to 80, by letters to undergo an ABI measurement. Consequently, in patients with ABI>1.4, an ultrasound evaluation of the peripheral and carotid arteries was performed. An ABI>1.4 was found in 260 of 3412 subjects (7.6%). Statistically significant differences were reported in age, diabetes and hypertension, body mass index (BMI) and waist circumference (WC). No differences in sex distribution, dyslipidemia and smoke prevalence were observed. Moreover, 67.9% of ABI>1.4 patients showed a peripheral intima-media thickness (IMT)>0.9 mm; at linear regression it was correlated with ABI values; 25% of patients showed peripheral plaques. A carotid IMT>0.9 mm was reported in 78.6% of high-ABI patients and 32.1% were affected by atherosclerotic plaques. The observed increased-ABI prevalence of 7.6% was higher than previously reported. This was more prevalent in an older population with diabetes, hypertension and obesity. Moreover, these patients are characterized by an extended atherosclerotic involvement. Further studies are needed to clarify this evidence, a longitudinal observation of this clinical outcome, as we are performing, could provide a number of interesting elements.

Study on unrecognized peripheral arterial disease (PAD) by ankle/brachial index and arterial comorbidity in Catania, Sicily, Italy.

Peripheral arterial disease (PAD) is under diagnosed and early diagnosis decreases consequences. We screened unrecognized PAD focusing on arterial co-morbidities. In the 3412 subjects, screened from 10 general practices in the city of Catania (Sicily, Italy), ankle brachial index (ABI) measurements were performed. An ABI < or =0.9 was considered as valid in diagnosing PAD. ABI value < or =0.9 was found in 2.3%, and a significant rate of carotid stenosis was also found Echocardiographic markers left ventricular diameter (LVD) >55 mm, interventricular septum (IVS) >11 mm, left ventricular diastolic volume (LVDV) was found > 100 ml), and ejection fraction (EF) was <50% were found with high frequency in those with ABI < or =0.9. Unrecognized PAD is lower compared with other findings but our prevalence resulted higher than other prevalence previously found by other study performed in Italy. Unrecognized PAD shows significant arterial co-morbidities and the ABI is a useful method to screen asymptomatic PAD.