Expanding the Neurological Phenotype of Ring Chromosome 10 Syndrome: A Case Report and Review of the Literature.

Ring chromosome 10 [r(10)] syndrome is a rare genetic condition, currently described in the medical literature in a small number of case report studies. Typical clinical features include microcephaly, short stature, facial dysmorphisms, ophthalmologic abnormalities and genitourinary malformations. We report a novel case of r(10) syndrome and review the neurological and neuroradiological phenotypes of the previously described cases. Our patient, a 3 year old Italian girl, represents the 20th case of r(10) syndrome described to date. Intellectual disability/developmental delay (ID/DD), microcephaly, strabismus, hypotonia, stereotyped/aggressive behaviors and electroencephalographic abnormalities were identified in our patient, and in a series of previous cases. A brain MRI disclosed a complex malformation involving both the vermis and cerebellar hemispheres; in the literature, posterior cranial fossa abnormalities were documented by CT scan in another case. Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems. Our case expands the neurological and neuroradiological phenotype of r(10) syndrome. Although r(10) syndrome represents an extremely rare condition, with a clinical characterization limited to case reports, the recurrence of specific neurological and neuroradiological features suggests the need for specific genotype-phenotype studies.

Neurological Phenotype of Mowat-Wilson Syndrome.

Mowat-Wilson Syndrome (MWS) (OMIM # 235730) is a rare disorder due to ZEB2 gene defects (heterozygous mutation or deletion). The ZEB2 gene is a widely expressed regulatory gene, extremely important for the proper prenatal development. MWS is characterized by a specific facial gestalt and multiple musculoskeletal, cardiac, gastrointestinal, and urogenital anomalies. The nervous system involvement is extensive and constitutes one of the main features in MWS, heavily affecting prognosis and life quality of affected individuals. This review aims to comprehensively organize and discuss the neurological and neurodevelopmental phenotype of MWS. First, we will describe the role of ZEB2 in the formation and development of the nervous system by reviewing the preclinical studies in this regard. ZEB2 regulates the neural crest cell differentiation and migration, as well as in the modulation of GABAergic transmission. This leads to different degrees of structural and functional impairment that have been explored and deepened by various authors over the years. Subsequently, the different neurological aspects of MWS (head and brain malformations, epilepsy, sleep disorders, and enteric and peripheral nervous system involvement, as well as developmental, cognitive, and behavioral features) will be faced one at a time and extensively examined from both a clinical and etiopathogenetic point of view, linking them to the ZEB2 related pathways.

Focal nonconvulsive status epilepticus in children: clinical and electroencephalographic features in 38 patients.

PURPOSE: The aim of this study was to characterize clinically, etiologically, and electroencephalographically focal Nonconvulsive Status Epilepticus (NCSE) in children. Moreover, we tried to identify focal NCSE features distinguishing between different ages, NCSE etiologies, and cases of de novo onset. METHODS: We retrospectively identified patients (aged 1 month to 18 years) who had EEG-documented focal NCSE between January 2001 and December 2019. We analyzed the clinical features, etiology, and EEG features of each event. RESULTS: Thirty-eight patients were included in this study. NCSE had a de novo onset in 26 patients and was the first manifestation of previously undiagnosed epilepsy in 12 patients. NCSE etiology was acute symptomatic in 13 patients. Acute symptomatic NCSE events were mainly observed in hospitalized children, were usually longer, and had a significantly higher frequency of repetitive EEG patterns than other etiologies. In patients with epilepsy, the etiology of NCSE was remote symptomatic in 14, progressive in 6, and cryptogenic in 5; a definite or suspected genetic disorder was observed in 11. EEG localization was frequent in posterior regions (18 children). Eleven patients had refractory NCSE and 4 required admission to the intensive care unit. CONCLUSION: Focal NCSE in children is more frequent in the first years of life, mainly involves posterior regions, and often has de novo onset. In the case of de novo focal NCSE both acute symptomatic NCSE and new-onset epilepsy must be considered and investigated. A higher frequency of repetitive EEG patterns and an inpatient setting are significantly associated with acute symptomatic NCSE.

Acute ataxia in paediatric emergency departments: a multicentre Italian study.

OBJECTIVES: To evaluate the causes and management of acute ataxia (AA) in the paediatric emergency setting and to identify clinical features predictive of an underlying clinically urgent neurological pathology (CUNP). STUDY DESIGN: This is a retrospective medical chart analysis of children (1-18 years) attending to 11 paediatric emergency departments (EDs) for AA in an 8-year period. A logistic regression model was applied to identify clinical risk factors for CUNP. RESULTS: 509 patients (mean age 5.8 years) were included (0.021% of all ED attendances). The most common cause of AA was acute postinfectious cerebellar ataxia (APCA, 33.6%). Brain tumours were the second most common cause (11.2%), followed by migraine-related disorders (9%). Nine out of the 14 variables tested showed an OR >1. Among them, meningeal and focal neurological signs, hyporeflexia and ophthalmoplegia were significantly associated with a higher risk of CUNP (OR=3-7.7, p<0.05). Similarly, the odds of an underlying CUNP were increased by 51% by each day from onset of ataxia (OR=1.5, CI 1.1 to 1.2). Conversely, a history of varicella-zoster virus infection and vertigo resulted in a significantly lower risk of CUNP (OR=0.1 and OR=0.5, respectively; p<0.05). CONCLUSIONS: The most frequent cause of AA is APCA, but CUNPs account for over a third of cases. Focal and meningeal signs, hyporeflexia and ophthalmoplegia, as well as longer duration of symptoms, are the most consistent 'red flags' of a severe underlying pathology. Other features with less robust association with CUNP, such as seizures or consciousness impairment, should be seriously taken into account during AA evaluation.

An observational study of fixed-dose Tanacetum parthenium nutraceutical preparation for prophylaxis of pediatric headache.

BACKGROUND: Migraine is one of the most prevalent chronic pain manifestations of childhood. Despite the multitude of available treatments, parents are often concerned about chronic therapies and pediatricians have insufficient confidence in prescribing prophylactic drugs. Therefore, there is now growing interest for natural supplements used to control recurrent migraine headaches. Such approach may increase acceptance and adherence to long-term prophylaxis therapy in children. METHODS: This is an observational multicenter study performed in children (n = 91) with migraine, with (MO) or without aura (MA), or tension-type headache (TTH). A fixed-dose Andrographis paniculata, CoQ10, riboflavin, and magnesium, was administered for 16 weeks. Patients were evaluated at baseline (T0), at week 8 (T1) and at the end of treatment at week 16 (T2). A follow-up period occurred at week 20 (T3) and week 32 (T4). RESULTS: The herbal supplement significantly reduced the frequency of headaches in TTH patients during treatment period (T0: 11.97 + 1.92 vs T2: 5.13 + 1.93; p < 0.001) and the efficacy was maintained after 16 weeks of treatment withdrawal (T4: 4.46 + 1.75; p < 0.001 vs T0). The frequency of migraine attacks was also reduced in the MO group during treatment (T0: 9.70 + 0.96 vs T2: 4.03 + 0.75; p < 0.01) and after withdrawal (T4: 2.96 + 0.65; p < 0.01 vs T0). Conversely, MA patients showed reduction in migraine's frequency during treatment (T0: 8.74 + 1.91 vs T2: 3.78 + 2.02; p < 0.01) but not at the end of the study (T4: 5.57 + 3.31; p > 0.05 vs T0). TTH patients did not report significant improvement of pain intensity. A significant effect was observed in the MO group during treatment (T0: 3.06 + 0.11 vs T2: 2.14 + 0.19; p < 0.001) and after treatment withdrawal (T4: 2.20 + 0.21; p < 0.001 vs T0). Likewise, MA group showed a significant treatment effect (T0: 2.57 + 0.20 vs T2: 0.86 + 0.45; p < 0.001) and the efficacy persisted at the end of the study (T4: 1.00 + 0.58; p < 0.001 vs T0). CONCLUSION: This fixed-dose Tanacetum parthenium preparation improved headache frequency and pain intensity in children affected by TTH. Despite the main limits, this study supports the use of nutraceutical in pediatric headache/migraine.

Long-term follow-up of cognitive functions in patients with continuous spike-waves during sleep (CSWS).

Continuous spike-waves during sleep (CSWS) are associated with several cognitive, neurological, and psychiatric disorders, which sometimes persist after CSWS disappearance. The purpose of this retrospective study was to investigate the correlation between general (clinical and instrumental) and neuropsychological findings in CSWS, to identify variables that predispose patients to a poorer long-term neuropsychological outcome. Patients with spikes and waves during sleep with a frequency ≥25/min (spikes and waves frequency index - SWFI) were enrolled. There were patients presenting abnormal EEG activity corresponding to the classic CSWS and patients with paroxysmal abnormalities during sleep <85% with SWFI ≥25/min that was defined as excessive spike-waves during sleep (ESWS). Clinical and instrumental features and neuropsychological findings during and after the spike and wave active phase period were considered. A statistical analysis was performed utilizing the Spearman correlation test and multivariate analysis. The study included 61 patients; the mean follow-up (i.e., the period between SWFI ≥25 first recording and last observation) was 7years and 4months. The SWFI correlated inversely with full and performance IQ during CSWS/ESWS. Longer-lasting SWFI ≥25 was related to worse results in verbal IQ and performance IQ after CSWS/ESWS disappearance. Other variables may influence the neuropsychological outcome, like age at SWFI ≥25 first recording, perinatal distress, pathologic neurologic examination, and antiepileptic drug resistance. This confirms that CSWS/ESWS are a complex pathology and that many variables contribute to its outcome. The SWFI value above all during CSWS/ESWS and long-lasting SWFI ≥25 after CSWS/ESWS disappearance are the most significant indexes that appear mostly to determine cognitive evolution. This finding underscores the importance of EEG recordings during sleep in children with a developmental disorder, even if seizures are not reported, as well as the importance of using therapy with an early efficacy.