Efterpi Pavlidou

Neurocutaneous Melanosis: Report of Three Cases and Up-to-date Review

Neurocutaneous melanosis is a rare noninherited embryonic neuroectodermal dysplasia, which is observed sporadically and never affects the entire integument. The hallmark of neurocutaneous melanosis in the neonatal period is the presence of a large bilateral hairy dark nevus with satellite nevi over the trunk and neck. The diagnosis should be considered in neonates with large pigmented nevi and in those with more than 3 hairy dark nevi regardless of their size. Neonates with neurocutaneous melanosis are at risk of developing neurological problems. The most common neurological complications are hydrocephalus, seizures, cranial nerve dysfunction, and signs of spinal cord and root involvement. The authors report 3 cases of histologically confirmed neurocutaneous melanosis and describe the course of neurological symptoms and clinical findings including cognitive tests and neuroimaging. The case reports are complemented by an up-to date review on this clinical entity.

Effectiveness of intermittent diazepam prophylaxis in febrile seizures : Long-term prospective controlled study

The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately.

Cerebral aspergillosis in an infant with corticosteroid-resistant nephrotic syndrome

Abstract.Cerebral aspergillosis is a devastating disease in patients with a compromised immune system. A unique case of a male infant with corticosteroid-resistant nephrotic syndrome complicated by pulmonary and cerebral aspergillosis is described. The patient rapidly developed coma and neurological symptoms and died soon thereafter. Central nervous system aspergillosis was diagnosed radiologically and by detection of Aspergillus DNA and antigen (galactomannan) in blood and cerebrospinal fluid. Moderate immunosuppressive therapy and antifungal phagocytic dysfunction due to nephrotic syndrome per se may have contributed to the occurrence of invasive aspergillosis in our patient. Awareness of this serious complication and early application of diagnostic procedures and antifungal therapy may improve the dismal outcome.

Prognostic factors for subsequent epilepsy in children with febrile seizures

Epilepsy following febrile seizures (FS) has been estimated between 2% and 7%. It concerns a prospective study in a large sample of children with a long‐term follow‐up. The aim of this study is to identify the prognostic factors that can lead children with FS to epilepsy.

Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency

BACKGROUND The term Pontocerebellar hypoplasias collectively refers to a group of rare, heterogeneous and progressive disorders, which are frequently inherited in an autosomal recessive manner and usually have a prenatal onset. Mutations in the SEPSECS gene, leading to deficiency in selenoprotein biosynthesis, have been identified in recent times as the molecular etiology of different pre/perinatal onset neurological phenotypes, including cerebello-cerebral atrophy, Pontocerebellar hypoplasia type 2D and progressive encephalopathy with elevated lactate. These disorders share a similar spectrum of central (e.g., brain neurodegeneration with grey and white matter both involved) and peripheral (e.g., spasticity due to axonal neuropathy) nervous system impairment. CASE PRESENTATION We hereby describe a 9-year-old boy with (i) a typical Pontocerebellar hypoplasia type 2D phenotype (e.g. profound mental retardation, spastic quadriplegia, ponto-cerebellar hypoplasia and progressive cerebral atrophy); (ii) optic nerve atrophy and (iii) mild secondary mitochondrial myopathy detected by muscle biopsy and respiratory chain enzyme analysis. We performed whole exome sequencing which identified a homozygous mutation of the SEPSECS gene (c.1001T > C), confirming the clinical suspect of Pontocerebellar hypoplasia type 2D. CONCLUSION This report further corroborates the notion of a potential secondary mitochondrial dysfunction in the context of selenoprotein biosynthesis deficiency and also adds optic nerve atrophy as a new potential clinical feature within the SEPSECS-associated clinical spectrum. These findings suggest the presence of a possible shared genetic etiology among similar clinical entities characterized by the combination of progressive cerebello-cerebral and optic nerve atrophy and also stress the biological importance of selenoproteins in the regulation of neuronal and metabolic homeostasis.

Lumbar puncture complicated by spinal epidural hematoma in a child with leukemia

We report a case of spinal epidural hematoma (SEH) preceded by diagnostic lumbar puncture (LP) in a 5‐year‐old boy with acute lymphoblastic leukemia. MRI confirmed the presence of SEH between T7 and L5 levels, but the patient showed fast recovery during the next hours and conservative management was elected.

Sleep respiratory parameters in children with idiopathic epilepsy: A cross-sectional study.

BACKGROUND The aim of this study is to explore and compare through polysomnography respiratory sleep parameters between children with idiopathic epilepsy and healthy children. METHODS Our cross-sectional study included 40 children with idiopathic epilepsy and 27 healthy children, who underwent overnight polysomnography. Data about sleep respiratory parameters were obtained and statistically analyzed. The level of statistical significance was set at 0.05. RESULTS The prevalence of Obstructive Sleep Apnea Syndrome was significantly higher in the epilepsy group (35% vs 7.4%, p<0.01). Moreover, the odds ratio of an obstructive apnea index ≥1 in the epilepsy group was 10.6 (95% Confidence Intervals: 3.08-37.08) in comparison to the control group. The mean value of the obstructive apnea-hypopnea index was significantly higher in children with epilepsy compared to healthy children (2.46±1.22 vs 1.21±0.83, p=0.027). The mean values of central apnea index and desaturation index were comparable between these two groups. Longest apnea duration was significantly higher in the group of poor seizure control. All other sleep respiratory variables did not differ significantly between children with poor and good seizure control and between children with generalized and focal epilepsy. CONCLUSIONS Children with epilepsy seem to present more prominent sleep breathing instability in comparison to healthy children, which mainly includes a predisposition to obstructive respiratory events. More studies are needed to investigate the relationship between sleep apneas and seizure control.

Postherpes simplex encephalitis: a case series of viral-triggered autoimmunity, synaptic autoantibodies and response to therapy

Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays. Results: Five patients (two infants, one child and two adults) developed post-HSV autoimmune encephalitis. The infants, aged 9 months and 10 months, after prompt and seemingly successful anti-HSV therapy, were readmitted with typical signs of NMDAR-encephalitis evolving within days, with NMDAR antibodies detected in both serum and CSF. Although they were promptly treated with intravenous immunoglobulin (IVIg) and with IVIg followed by rituximab, respectively, they were both left with psychomotor deficits. A 14-year-old girl with seizures due to HSV encephalitis improved with anti-HSV therapy. Later, she manifested intractable seizures and she was found positive for anti-NMDAR antibodies which persist. The two adults were women, aged 58 and 33 years. The first recovered after anti-HSV therapy and remained asymptomatic for 6 months, until she developed generalized seizures with persisting CSF anti-NMDAR antibodies; the second, who continued to be encephalopathic after 2 weeks of anti-HSV therapy, tested positive for anti-NMDAR antibodies in the serum and anti-GABAbR antibodies in the serum and CSF. She recovered fully following IVIg therapy but her serum anti-GABAbR antibodies persist 34 months later. Discussion: Infection of the CNS with HSV can trigger CNS autoimmunity associated not only with anti-NMDAR but also with anti-GABAbR antibodies. These antibodies can persist in the serum, even without associated symptoms, but their presence in the CSF is firmly associated with disease development. In contrast to children and adults who responded well to therapies, the infants had an incomplete recovery with severe psychomotor deficits probably due to the interference of anti-NMDAR antibodies with neuro-developmental processes.

Ischemic cerebral infarction in a 5-year-old male child with neurofibromatosis type 1

Stroke is a common cause of neurological disease in children and ranks in the top ten causes of death in the USA, with poor outcome and neurological deficits for the survivors. The annual incidence of pediatric stroke is estimated from 1.3 to 13 cases out of 100,000 population [1]. The broad definition of pediatric stroke includes ischemic and hemorrhagic stroke. In childhood, 55 % of stroke is ischemic and 45 % hemorrhagic, whereas in adults, 85 % of stroke is ischemic [2]. According to the World Health Organization, “ischemic stroke” is a clinical syndrome of rapidly developing focal or global disturbance of brain function lasting more than 24 h or leading to death, caused by arterial or venous infraction (thrombosis or embolism) [3]. Arterial ischemic/hemorrhagic strokes in children usually concern anterior and middle cerebral arteries and their brunches, as also the thalamus and basal ganglia [1]. Children with stroke usually present with hemiparesis, sensory disorders (hemianesthesia), and visual disturbance (hemianopia). Headache is usually present with hemorrhagic stroke, post-traumatic arterial thrombosis, and venous thrombosis. Altered levels of consciousness indicate intracranial hemorrhage, ischemic infarction of the middle cerebral artery, or extensive infarct in the posterior circulation. Seizures mainly occur in cerebral venous sinus thrombosis, most frequently in the neonatal period. Acute onset of clinical presentation usually indicates embolism or acute thrombosis due to posttraumatic rupture of the arterial endothelium, while subacute onset of clinical presentation usually indicates progressive thrombosis [4, 5]. Generally, clinical presentation of pediatric stroke is age dependent. It is also varied and nonspecific, encompassing a broad differential diagnosis. So, the diagnosis of stroke in childhood is often delayed and is rarely made within 6 h of symptom onset [6]. We describe a case of a 5-year-old male child who presented to our clinic with acute right pyramidal tract signs. The aim of this case presentation is to point out the importance of early recognition of pediatric stroke and also to discuss the possible association of neurofibromatosis type 1 (NF1) with intracranial arterial anomalies and problems of blood coagulation.

Benign Infantile Epilepsy Mimicking Reflex Anoxic Seizures in an Infant with PRRT2 Gene Mutation

To the Editor: A 12-mo-old Caucasian girl presented with recurrent seizures since the age of nine months. She was the first child of non-consanguineous parents. Shewould become vacant with facial pallor, occasional lips cyanosis and isolated upper limb jerky movement. A tonic stiffening of upper limbs, myoclonic movements of fingers and facial musculature contraction would follow after five minutes. She would then fall asleep for two hours. The triggers were difficult to identify, but speculated to include frustration, fright or a feeling of abandonment. Neurological examination was normal. Routine, sleepdeprived and 24-h electroencephalography (EEG) telemetry study were all reported as normal. Brain MRI did not reveal any pathological findings and cardiac investigations were also normal. Given the unusual presentation, a genetic cause was suspected. Targeted sequence analysis of the PRRT2 gene, the leading cause for paroxysmal disorders, detected the exon 2 c.649dupC p.(Arg217Profs*8) PRRT2 variant in the heterozygous state. The father was found to share the samemutation. PRRT2 encodes for the proline-rich transmembrane protein 2 in the developing nervous system and interacts with synaptosomal associated protein 25 (SNAP-25), involved in the interaction of Ca2 + −triggered release of neurotransmitters at the presynaptic terminals [1]. To date, some 1500 patients with approximately seventy different PRRT2 mutations have been reported. Of these, 5.5% (79/1444) occurred de novo, while 87.1% (1258/1444) are familial in origin [2]. PRRT2 mutations have been mainly associated with Benign Familial Infantile Epilepsy, Paroxysmal Kinesigenic Dyskinesia and Infantile Convulsions and Choreoathetosis [2] and lately with benign myoclonus of early infancy [3] and paroxysmal hypnogenic dyskinesia (PHD) [4]. At 25 mo of age, the child has been seizure free with a normal psychomotor development and no anticonvulsant medications. Though her presentation was highly evocative of reflex anoxic seizures, her clinical phenotype and the PRRT2 loss of function mutation corroborated the diagnosis of a benign form of epilepsy, according to ILAE classification of 2010 [5]. Currently, PRRT2 physiological function remains unclear, even though a marked pleiotropy and variable penetrance of its mutations are well-described. Our case herein concurs in expanding the clinical spectrum of PRRT2 related disorders.