Hypertrophic olivary degeneration in a 16-year-old girl after subtotal surgery of a brainstem pilocytic astrocytoma : a case report

Purpose: Hypertrophic olivary degeneration (HOD) is a unique neurological condition caused by interruption of the dentato-rubro-olivary pathway, also known as the triangle of Guillain and Mollaret. Magnetic resonance (MR) imaging is the best modality to diagnose both the degeneration of the inferior olivary nucleus and the underlying cause. Case report: We describe a case of a unilateral HOD in a 16-year-old girl several months after a subtotal excision of a brainstem pilocytic astrocytoma. Taking into account the patient's history, tumour recurrence must have been considered, but the typical location and MR morphology, as well as the time of occurrence after brainstem surgery, contributed to the diagnosis of HOD. The causative factor was the interruption of the central tegmental tract, which forms one arm of the Guillain and Mollaret triangle. Additionally, this is an interesting case of a child, who stayed in a coma for several months following brainstem surgery, but finally was discharged home with only minor neurological defects and returned to normal life. Conclusions: Hypertrophic olivary degeneration is an infrequent neurological condition, especially in the paediatric population. Nevertheless, it should be considered when interpreting late postoperative scans of children with a history of a brain tumour

Neurochirurgiczne leczenie lekoopornej padaczki na podstawie fuzji obrazów MR i SPECT : opis przypadku

Background: Epilepsy concerns at least 0.5% of population and in most of the cases (approx. 70%) can be treated pharmacologically, which helps to prevent seizures. In all other patients, such a treatment does not produce the desired results. Their condition may require neurosurgical management. The aim of this work was to fuse anatomical MRI images and functional SPECT images in patients with drugresistant epilepsy, without structural changes on MRI or with changes so severe that it would be impossible to establish which ones are responsible for seizures. The authors presented a case of a child subjected to a neurosurgical procedure carried out on the basis of the fused MRI and SPECT images. Case Report: A seven-year-old boy with an extensive defect of the right hemisphere (cortical dysplasia with multiple balloon-like cells) operated on three times due to a history of treatment-resistant seizures present since the age of one. A subsequent MRI examination was performed with magnetic field intensity of 1.5 T, within a routine epilepsy protocol applying volumetric thin-slice T1-weighted images. Next, in the interictal period, a SPECT examination was performed with the use of the 99mTc-labelled ethyl cysteinate dimer (99mTcECD). For fusion and postprocessing, the following software was used: PMOD (Biomedical Image Quantification PMOD Technologies) with PFUS (Flexible Image Matching and Fusion Tool) and a program for a quantitative analysis of counts in the region of interest, so called VOI Constructor (Volume of Interest Constructor). On the basis of the fusion of images, the boy was subjected to the next operation procedure. The remaining fragments of the right frontal and parietal lobe adjacent to the occipital lobe were removed. Seizure remission was obtained and it was already 31 months long when we were writing this article. Conclusions: Owing to this multi-stage procedure, it was possible to avoid a total anatomical and functional hemispherectomy. This allowed for a resection limited to regions indicated by integrated imaging. Removal of cortical areas including lesions was advantageous in this presented case, as it allowed for saving active regions of the brain

Wczesnoniemowlęca encefalopatia padaczkowa 19 z dyskinezami uwarunkowana nową mutacją w genie GABRA1 – pierwszy przypadek w polskiej populacji

Background: Dominant, heterozygous mutations in the GABRA1 gene on chromosome 5q34 cause a heterogeneous, constantly growing group of neurological disorders. Aim: The aim of the study was to report on an individual with profound psychomotor retardation, extrapyramidal symptoms and epilepsy due to a new mutation in GABRA1 gene (c.799C>A). Material and Methods: The child with unremarkable family and perinatal history, fetal and perinatal primary microcephaly, delayed psychomotor development in a profound degree as well as with impaired global physical development and a failure to thrive. From the first months of life dyskinesias, bruxism, upward eye deviation and oropharyngeal movements were present. However, on sleep EEG generalized spike and wave discharges were present. Whole-exome sequencing (WES) was carried out in the proband. Results: WES results detected disease-causing novel mutation in the GABRA1 gene, the first case in the Polish population. Conclusions: Our observation expands the spectrum of syndromes of EIEE19 associated with GABRA1 gene mutations. This mutation (c.799 C>A) has not been described previously in the literature.Wstęp: Dominujące, heterozygotyczne mutacje w genie GABRA1 zlokalizowanym na chromosomie 5q34 powodują zróżnicowaną, stale powiększającą się grupę zaburzeń neurologicznych. Cel pracy: Celem pracy jest przedstawienie fenotypu pacjenta z opóźnieniem rozwoju psychoruchowego w stopniu głębokim, objawami pozapiramidowymi oraz padaczką, uwarunkowanych nowo powstałą mutacją w genie GABRA 1 (c.799C>A). Materiał i Metody: Dziecko z nieobciążonym wywiadem rodzinnym, płodowo-okołoporodowym, pierwotnym małogłowiem, opóźnionym rozwojem psychoruchowym w stopniu głębokim jak również z zaburzonym rozwojem fizycznym. Od pierwszych miesięcy życia obserwowano: dyskinezy, bruksizm, zwroty gałek ocznych ku górze, ruchy orofaryngealne. W zapisie EEG we śnie stwierdzono zmiany napadowe uogólnione iglica fala. W celu identyfikacji genów odpowiadających za fenotyp przeprowadzono sekwencjonowanie całego eksomu (WES). Wyniki: Badanie metodą WES wykazało mutację w genie GABRA1, odpowiadającą za chorobę – pierwszy przypadek w polskiej populacji. Wnioski: Opis naszego przypadku poszerza spektrum objawów EIEE19 powiązanych z mutacjami w genie GABRA1. Mutacja (c.799C>A) nie została jak dotychczas opisana w literaturze

Genetic Risk Factors for Neurological Disorders in Children with Adverse Events Following Immunization: A Descriptive Study of a Polish Case Series

Studies conducted on large populations show a lack of connection between vaccination and serious neurological symptoms. However, there are isolated cases that indicate such a relationship. These reports on adverse effects following immunization (AEFI) reduce social confidence in vaccination; however, their background may be rare genetic defects. The aim of the presented study was to examine if neurological AEFI in children may be associated with variants in genes related to neurodevelopment. To identify such possible associations, a descriptive study of the Polish case series was conducted. We performed next-generation sequencing in patients who, up to 4 weeks of injection of any vaccine, manifested neurological AEFI. We included 23 previously normally developing children with first seizures that occurred after vaccination. We identified pathogenic/likely pathogenic variants in genes engaged in neurodevelopment in nine patients and variants of uncertain significance in another nine patients. The mutated genes belonged to the group of genes related to epilepsy syndromes/epileptic encephalopathy. We showed that AEFI might have a genetic background. We hypothesized that in some AEFI patients, the vaccine might only trigger neurological symptoms that would have been manifested anyway as a result of a pathogenic variant in a gene engaged in neurodevelopment

PIGN encephalopathy: Characterizing the epileptology

International audienceOBJECTIVE: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. METHODS: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. RESULTS: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. SIGNIFICANCE: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment

PIGN encephalopathy: Characterizing the epileptology

International audienceOBJECTIVE: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. METHODS: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. RESULTS: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. SIGNIFICANCE: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment

PIGN encephalopathy : characterizing the epileptology

International audienceOBJECTIVE: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. METHODS: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. RESULTS: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. SIGNIFICANCE: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment