Grazia Gabriella Salerno

Vagus nerve stimulation during pregnancy: an instructive case

BackgroundLittle is known about the safety of vagus nerve stimulation during pregnancy.Case ReportHerein we report the case of a young woman affected by childhood-onset partial epilepsy, obesity, and depression in which a malfunctioning of VNS was detected during pregnancy. Although device functioning was not optimal during the critical period of organogenesis, no morphological abnormalities of the fetus were detected.ConclusionA confirmation of VNS safety may increase its use during pregnancy, thus reducing possible systemic effects of antiepileptic drugs and antidepressants on the women and the baby.

Expanding phenotype of PRRT2 gene mutations: A new case with epilepsy and benign myoclonus of early infancy.

BACKGROUND Mutations in the gene PRRT2 have been identified in a variety of early-onset paroxysmal disorders. To date associations between PRRT2 mutations and benign myoclonus of early infancy have not been reported. CLINICAL REPORT We describe a baby affected by PRRT2 mutation and benign infantile epilepsy, with an episode of focal status epilepticus. During follow-up he developed benign myoclonus of early infancy. DISCUSSION We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia. CONCLUSIONS Currently the function of PRRT2 is poorly understood, even if a marked pleiotropy and variable penetrance of its mutations are well known. Our case concurs in expanding the broad clinical spectrum of PRRT2-related disorders.

CMV-associated axonal sensory-motor Guillain-Barré syndrome in a child: Case report and review of the literature.

BACKGROUND Guillain-Barré syndrome is the most frequent cause of flaccid paresis in Western countries. Moreover, CMV infection is the most common antecedent viral infection in adult patients and the presence of specific IGM antiganglioside antibodies is often identified. Instead, Guillain-Barré syndrome following CMV infections is rarely reported in childhood and often presents severe symptoms at onset and longer recovery times. MATERIAL AND METHODS One year of clinical, electrophysiological and serological follow-up of a 9-year old child with axonal sensory-motor Guillain-Barré syndrome following CMV infection is reported. Moreover, the literature data on paediatric sensory-motor axonal GBS and GBS secondary to CMV infection and antiganglioside antibodies are reviewed. RESULTS Our patient presented with paraesthesias and a pattern of weakness showing proximal predominance and affecting the upper limbs more than the lower limbs. At nadir, unilateral facial palsy was also present and he was unable to walk. Electroneurography showed motor-sensory axonal damage. Both anti-CMV and anti-GM2 IgM were positive. After early treatment with IVIG and IV methylprednisolone the patient recovered deambulation. Six months later, his neurological examination was normal and electroneurography showed normal data. CONCLUSION The sensory-motor axonal form of Guillain-Barré syndrome following CMV infection may present a good prognosis and a prompt full recovery also in children, if adequate treatment is started in time.

KCNQ2 encephalopathy: A case due to a de novo deletion

KCNQ2 encephalopathy is characterized by severely abnormal EEG, neonatal-onset epilepsy and developmental delay. It is caused by mutations (typically missense) in the KCNQ2 gene, encoding the voltage gated potassium channel Kv7.2 and leading to a negative-dominant effect. We present one case experiencing recurrent neonatal seizures with changing hemispheres of origin, reminiscent of epilepsy of infancy with migrating focal seizures. At 9months of age the patient is still seizure-free on carbamazepine, although he is developing a spastic-dystonic tetraplegia with severe dysphagia. He harbors a de novo deletion (c.913_915del [p.Phe305del)]), only described once in a couple of severely affected twins, and leading to the deletion of a phenylalanine residue in the pore domain of the channel. In conclusion, our case is the second described with encephalopathy due to this specific deletion (the one and only deletion so far reported in KCNQ2 encephalopathy). Thus, deletion is a newly described mechanism highlighting how not only missense mutations but also deletions in the channel hot spots can lead to a severe phenotype. Furthermore he presented ictal EEG features similar to epilepsy of infancy with migrating focal seizures not previously described.

Long-term follow-up in spastic paraplegia due to SPG56/CYP2U1: age-dependency rather than genetic variability?

We read with great interest the paper by Leonardi et al. [1] which presented an Italian family harboring a novel homozygous mutation in SPG56/CYP2U1 with pigmentary degenerative maculopathy as a prominent feature. SPG56, due to CYP2U1 mutation, is a rare autosomal recessive early-onset complicated form of hereditary spastic paraplegia with spasticity in the upper limbs, rare dystonic postures, cognitive impairment and subclinical neuropathy [2]. The phenotypic spectrum of SPG56 has been recently expanded: 18 subjects have currently been reported with increasing clinical and neuroradiological heterogeneity [1–6]. We would like to present a further case with two novel mutations in in CYP2U1 gene and pigmentary degenerative maculopathy to highlight how the phenotypic variability so far reported might also be age-dependent and not only related to genetic heterogeneity. This 34-year-old patient was the first daughter of healthy non-consanguineous Caucasian parents. During the long-term follow-up started since the first year of age, she underwent different genetic and neurometabolic investigations. We finally identified thanks to targeted re-sequencing TruSeq Custom Amplicon panel (MiSeq Illumina platform) formed by 21 idiopathic intracranial calcification genes two novel heterozygote mutations in SPG56/CYP2U1 gene: a c.1288?1G[A splicing mutation (exon 3) and a c.1545_1546delTTAC frameshift mutation (exon 5). The segregation of the mutations in the family was confirmed by DNA analysis of the parents. To prove pathogenicity of the mutations we conducted studies through the Next Generation Sequencing of the cDNA of CYP2U1 extracted from patient fibroblasts, evidenced the absence of the allele containing the 4 bp deletion and a significative exon 3 skipping. Until 14 years of age, our patient did not show the described pigmentary maculopathy on the retina, although she had already developed macular haemorrhagic lesions. Moreover, delayed flashing lights and P100 in visualevoked potentials only appeared after 10 years of age. Differently from our case and the case reported by Leonardi et al. [1], in other descriptions ophthalmological examinations were unremarkable [3, 4], probably because subjects were in the pediatric age, whereas in the cases reported by Tesson et al. no information about ophthalmological features were available [1]. In our patient, normal developmental milestones were reported until 14 months, when her motor skills began to deteriorate rapidly for the first 3 years and subsequently slowed down in progression. Since 16 months of age, she developed four limbs spasticity, more remarkable in the lower limbs, with ‘‘bottom to top’’ progression. After the age of 4 years appeared dysarthria and focal dystonic postures of the upper limbs probably due to the basal ganglia involvement. In the time of the last evaluation at 34 years old, she was on a wheelchair due severe spasticity with joint contractures especially in a lower limbs and presented swallowing difficulties. These appear to be & Alessandro Iodice alle.iodice@gmail.com

Infantile neuroaxonal dystrophy and PLA2G6-associated neurodegeneration: An update for the diagnosis

Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder characterized by infantile onset of rapid motor and cognitive regression and hypotonia evolving into spasticity. Recessively inherited mutations of the PLA2G6 gene are causative of infantile neuroaxonal dystrophy and other PLA2G6-associated neurodegeneration, which includes conditions known as atypical neuroaxonal dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive impairment. Phenotypic spectrum continues to evolve and genotype-phenotype correlations are currently limited. Due to the overlapping phenotypes and heterogeneity of clinical findings characterization of the syndrome is not always achievable. We reviewed the most recent clinical and neuroradiological information in the way to make easier differential diagnosis with other degenerative disorders in the paediatric age. Recognizing subtle signs and symptoms is a fascinating challenge to drive towards better diagnostic and genetic investigations.

Steroids efficacy in the acute management of seizure clusters in one case of PCDH19 female epilepsy

We read with great interest the paper entitled ‘‘Immediate suppression of seizure clusters by corticosteroids in PCDH19 female epilepsy’’ by Higurashi et al. [1]. Clusters of febrile and afebrile seizures, mainly focal motor or hypomotor with affective symptoms, are typical of PCDH19 female epilepsy (PCDH19-FE) [2]. After first reporting on the excellent efficacy of corticosteroids in acute cluster termination in one

Ocular flutter, generalized myoclonus, and ataxia associated with anti-GM1, GD1a, and GD1b antibodies in a 6-year-old child

Dear Editor-in-Chief, Ocular flutter is a rare oculomotor symptom characterized by back-to-back horizontal conjugate saccades, limited to one plane and without intersaccadic interval [1]. Ocular flutter is clinically distinct from opsoclonus, which presents irregular multi-directional movements, but both symptoms often manifest along with myoclonus and ataxia [1]. The causes of both these conditions include parainfectious autoimmune encephalitis, metabolic toxic states, demyelinating diseases, and paraneoplastic conditions (primarily neuroblastoma in children) [1]. However, often, the cause remains unknown [1]. The clinical syndrome of ocular flutter, stimulus sensitive myoclonus, and truncal ataxia has been considered to share a common pathophysiology with paraneoplast ic or postinfectious autoimmunity, and in some cases, it seems to be related to specific antiganglioside antibodies [2]. Its presence in a patient with antiganglioside antiGQ1b antibodies has been previously described only in a single adult patient [2]. A 6-year-old Chinese boy was admitted to our Neurologic Unit with ocular flutter, generalized myoclonus, and truncal ataxia. These symptoms appeared abruptly the day before the admittance. The boy had been suffering from hand-foot-andmouth disease for a few days, 8 days before. He was born to healthy non-consanguineous parents, and the perinatal history was unremarkable. Motor and mental developmental milestones were normally achieved. He had no significant past medical history or family history. On admission, neurological examination revealed periodic, rapid, conjugated oscillations of the eyes with a strict preponderance for the horizontal plane (ocular flutter) (video 1). Moreover, he presented an intense stimulus sensitive myoclonus, more pronounced in the neck and arms, which was provoked by sitting on the bed and ceased when he was lying down. A similar intense myoclonic response was also seen in response to intense and unexpected auditory stimuli (i.e., door slamming, hand clapping). Truncal ataxia with titubation was also evident, therefore he was not able to sit or walk unsupported. The remaining neurological evaluation showed normal cognition, bilateral flexor plantar responses, and normally evocated deep tendon reflexes. Brain, spinal, abdominal, and thoracic magnetic resonance imaging (MRI) were unremarkable; no gadolinium enhancement was found. Electroencephalogram (EEG) and electroneurography (ENG) were normal. Red and white blood cell counts, and biochemistry, free T4, free T3, thyrotropin, thyroglobulin, anti-thyrotropin receptor, and anti-thyroglobulin antibody were normal. Infectivologic screening was negative for serum antibodies against adenovirus, toxoplasma gondi, cytomegalovirus, herpes simplex virus (1 and 2), Chlamydia pneumoniae , Mycoplasma pneumoniae, Epstein-Barr virus, and influenza A and B viruses. Antiphospholipid antibodies were negative as well as ANA, ANCA, and anti-neuronal immunological reaction. Stool culture was negative for Shigella and Campylobacter infection as it was for virus isolation. Plasmatic analysis confirmed the recent Coxackie virus infection with specific high IgM and very high IgG titer. Neuron-specific enolase and a 24-h urine vanillylmandelic and homovanillic acid collection for neuroblastoma evaluation were negative. Plasmatic research of anti-GQ1B and GM2 ganglioside, anti-N-methyl-D-aspartate (NMDA) Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-018-3476-1) contains supplementary material, which is available to authorized users.