Novel insights into the clinico-radiological spectrum of phenotypes associated to PIGN mutations.

OBJECTIVES: Autosomic recessive mutations in the PIGN gene have been described in less than 30 subjects to date, in whom multiple congenital anomalies combined with severe developmental delay, hypotonia, epileptic encephalopathy, and cerebellar atrophy have been described as crucial features. A clear-cut neuroradiological characterization of this entity, however, is still lacking. We aim to present three pediatric PIGN mutated cases with an in-depth evaluation of their brain abnormalities. METHODS: We present the neuroradiological, clinical, and genetic characterization of three Caucasian pediatric subjects with pathogenic/likely pathogenic variants in the PIGN gene revealed by Next Generation Sequencing analysis. RESULTS: We identified three subjects (two siblings, one unrelated case) presenting with encephalopathy with early-onset epilepsy, hypotonia, and severe global developmental delay. No additional severe multiple congenital anomalies were detected. Neuroradiological evaluation showed extensive quantitative reduction of white matter, severe and progressive cortical atrophy, with frontal predominance and an anteroposterior gradient, combined with cerebellar and brainstem atrophy. CONCLUSIONS: Our findings broaden and systematize the neuroradiological spectrum of abnormalities in PIGN related encephalopathy. Furthermore, our dataset confirms that mutations in PIGN gene appear to be pan-ethnic and represent an underestimated cause of early-onset encephalopathy.

Migraine Symptoms Improvement During the COVID-19 Lockdown in a Cohort of Children and Adolescents.

Background: Pediatric migraine is among the most common primary or comorbid neurologic disorders in children. Psychological stressors are widely acknowledged as potential triggers involved in recurring episodes of pediatric migraine. As the COVID-19 emergency may have affected the levels of stress perceived by children and adolescents with migraine, the present study was aimed to understand the effect of COVID-19 emergency on symptoms intensity and frequency in pediatric patients. Methods: A cohort of 142 child and adolescent patients with a diagnosis of migraine was enrolled at the Child Neurology and Psychiatry Unit of the IRCCS Mondino Foundation in Pavia (Italy). Socio-demographic and clinical characteristics were obtained from medical records. An on-line survey was used to collect information on COVID-19 exposure, stress response to the lockdown period, anxious symptoms during COVID-19 emergency, as well as migraine symptoms intensity and frequency before and during the lockdown. Results: The great majority were outpatients (n = 125, 88.0%), 52 (36.6%) had migraine with aura, whereas, 90 (63.4%) had migraine without aura. All the patients reporting worsening symptoms progression before COVID-19, had reduced intensity during the lockdown (χ2 = 31.05, p < 0.0001). Symptoms frequency reduction was observed in 50% of patients presenting worsening symptoms before the lockdown, 45% of those who were stable, and 12% of those who were already improving. All patients who had resolved symptoms before COVID-19 were stable during the lockdown (χ2 = 38.66, p < 0.0001). Anxious symptomatology was significantly associated with greater migraine symptoms frequency (χ2 = 19.69, p < 0.001). Repeating the analysis separately for individuals with and without aura did not affect the findings and significant associations were confirmed for both the patients' subgroups. Discussion: A significant reduction of migraine symptoms intensity and frequency was observed in pediatric patients during the COVID-19 lockdown phase in northern Italy. The improvement in both intensity and frequency of the migraine symptoms was especially significant in patients who were stable or worsening before the lockdown. The reduction of symptoms severity during a period of reduced environmental challenges and pressures further highlights the need of providing effective training in stress regulation and coping for these patients.