The Neonatal Withdrawal Assessment Tool (NWAT): pilot inter-rater reliability and content validity.

OBJECTIVE: There is no validated tool to assess iatrogenic opioid withdrawal in preterm infants in the newborn intensive care unit (NICU). STUDY DESIGN: The Neonatal Withdrawal Assessment Tool (NWAT) was developed to address this gap in clinical practice. In this pilot study, the NWAT was assessed for inter-rater reliability (IRR) and content validity. RESULT: Fifty-one NICU providers scored two standardized simulated cases, then 20 paired provider assessments were completed on 5 preterm infants. The overall IRR was 95.6% on the simulated cases, and 98.8% on the 5 pilot infants. A provider survey assessed for content validity; all of the provider participants strongly agreed/agreed that the NWAT adequately measures withdrawal in critically ill infants. CONCLUSION: The NWAT demonstrated high IRR and content validity for assessment of iatrogenic opioid withdrawal in preterm infants in this pilot study. Further studies in a larger more diverse patient population are needed before wider adoption into clinical practice.

Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.

OBJECTIVE: Joubert syndrome is a neurodevelopmental disorder with a distinctive hindbrain malformation called molar tooth sign, causing motor and cognitive impairments. More than 40 genes have been associated with Joubert syndrome. We aim to describe a group of Joubert syndrome patients clinically and genetically emphasizing organ involvement. METHODS: We retrospectively collected clinical information and molecular diagnosis data of 22 patients with Joubert syndrome from multiple facilities. Clinical exome or whole-exome sequencing were performed to identify causal variations in genes. RESULTS: The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma. Portal hypertension and esophageal varices as liver and polycystic kidney disease and nephronophthisis as kidney involvement was encountered in our patients. The HYLS1 gene, which commonly causes hydrolethalus syndrome 1, was also associated with Joubert syndrome in one of our patients. A mild phenotype with hypophyseal hormone deficiencies without the classical molar tooth sign was observed with compound heterozygous and likely pathogenic variants not reported before in the KATNIP gene. CONCLUSION: Some rare variants that display prominent genetic heterogeneity with variable severity are first reported in our patients. In our study of 22 Joubert syndrome patients, CPLANE1 is the most affected gene, and Joubert syndrome as a ciliopathy is possible without a classical molar tooth sign, like in the KATNIP gene-affected patients.

Seizure treatment with olfactory training: a preliminary trial.

OBJECTIVE: Epilepsy is a chronic condition characterized by recurrent seizures. Despite miscellaneous antiseizure medications, resistance to treatment is still approximately 30%. This resistance brings forward the multidisciplinary approach and complementary treatments. In this study, we aimed to investigate the effect of olfactory training on epileptic seizures with special aromas having antiseizure effects in patients diagnosed with drug-resistant epilepsy. METHODS: A total of 24 patients (14 pediatric and 10 adults) with drug-resistant epilepsy were recruited for the study. Participants were asked to inhale the standardized bottle filled with lavender aroma (Lavandula Angustifolia) twice a day (morning and evening) for 30-45 s (2 cm in front of nose; 10-15 s to right and left nostril and 10-15 s to both nostrils) for 3 months. The type, frequency, duration of seizures, the quality of life (SF-36 and PedsQL 4.0), and olfactory functions (Sniffin' Sticks Test and Pediatric Smell Wheel) were re-assessed. RESULTS: Statistical analysis showed that olfactory training decreased the seizure frequency (p < 0.001) and the seizure duration (p = 0.02). A global 50% seizure reduction was seen among patients. Moreover, olfactory training increased the quality of life (p = 0.003) and improved the olfactory function in both the pediatric and adult groups (p = 0.017, p = 0.05, respectively). There was no adverse reaction and no increase in seizure frequency. SIGNIFICANCE: The observations of the present investigation suggest that olfactory training is a successful complementary therapy with no adverse reaction in patients with drug-resistant epilepsy. Large cohort studies and longer follow-up periods are needed for providing olfactory training as a therapy modality in patients with epilepsy.

Therapeutic plasma exchange in pediatric patients with acute demyelinating syndromes of the central nervous system: A single-center experience.

BACKGROUND: Therapeutic plasma exchange (TPE) is an extracorporeal treatment that can be used in adult and pediatric patients with acute demyelinating syndromes of the central nervous system. In this study, the efficacy and safety of TPE was evaluated in 10 pediatric patients who underwent TPE that were unresponsive to corticosteroid treatment. METHODS: Records of 10 pediatric patients who underwent TPE in our pediatric intensive care unit (PICU) between May 2017 and June 2020 were used. Expanded Disability Status Scale (EDSS), Gait Scale (GS), and Visual Outcome Scale (VOS) were applied to the patients before and after TPE. RESULTS: Of the 10 patients who underwent TPE, five were diagnosed with multiple sclerosis (MS), three with transverse myelitis (TM), and two with acute disseminated encephalomyelitis (ADEM). The median age of the patients was 13.3 years (IQR 8-15), and the median day from symptom onset to onset of TPE was 12.5 days (IQR 7-28). A total of 104 TPE sessions were performed successfully. While no complications were encountered in three patients during the sessions, the most common complication was hypofibrinogenemia. The decrease in EDSS and GS scores was found to be consistent with the clinical response of the patients. There was no statistically significant decrease in the VOS. CONCLUSIONS: With this study, we can say that TPE is a feasible, effective, and safe treatment modality in children with acute demyelinating syndromes of the central nervous system.

Pseudotumor Cerebri Syndrome as a Neurologic Involvement of Multisystem Inflammatory Syndrome in Children: A Case Report.

BACKGROUND: Coronavirus disease 2019 may have neurological manifestations including meningitis, encephalitis, post-infectious brainstem encephalitis and Guillain-Barre syndrome. Neuroinflammation has been claimed as a possible cause. Here, we present a child with multisystem inflammatory syndrome in children (MIS-C) who developed pseudotumor cerebri syndrome (PTCS) during the disease course. CASE: A 11-year-old girl presented with 5 days of fever, headache and developed disturbance of consciousness, respiratory distress, conjunctivitis and diffuse rash on her trunk. Immunoglobulin M and G antibodies against severe acute respiratory syndrome coronavirus 2 were positive in her serum. She was diagnosed with MIS-C. On day 10, she developed headache and diplopia. Left abducens paralysis and bilateral grade 3 papilledema were observed. Brain magnetic resonance imaging revealed optic nerve head protrusion, globe flattening. She was diagnosed with secondary PTCS. Papilledema and abducens paralysis improved under acetazolamide and topiramate. Neurological examination became normal after 2 months. CONCLUSION: PTCS may emerge related to MIS-C.

COVID-19-associated Acute Disseminated Encephalomyelitis-like Disease in 2 Children.

BACKGROUND: The coronavirus disease 2019 pandemic was caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the predominant clinical presentation is a respiratory disease, neurologic manifestations are being recognized increasingly. CASE REPORT: We report 2 children 9 years of age who developed acute disseminated encephalomyelitis-like disease associated with SARS-CoV-2. Seizures and encephalopathy were the main central nervous system symptoms. The cerebrospinal fluid analysis performed within the first week of disease onset showed elevated protein in both children with normal cell count and no evidence of infection including negative SARS-CoV-2 by antibody and polymerase chain reaction. Brain magnetic resonance imaging revealed T2A, fluid-attenuated inversion recovery cortical and subcortical hyperintensity without restricted diffusion consistent with acute disseminated encephalomyelitis-like disease. They received methylprednisolone followed by therapeutic plasma exchange. One of them showed complete clinical improvement and resolution in magnetic resonance imaging findings. The other developed laminar necrosis in brain magnetic resonance imaging and showed significant clinical improvement after therapeutic plasma exchange. He was positive for positive SARS-CoV-2 antibody in cerebrospinal fluid on day 55 of admission. They were both positive for SARS-CoV-2 antibodies in serum after 2 weeks. CONCLUSIONS: Our two cases highlight the occurrence of acute disseminated encephalomyelitis-like disease as a postinfectious/immune-mediated complication of SARS-CoV-2 infection.

Cytotoxic lesions of the corpus callosum in children: Etiology, clinical and radiological features, and prognosis.

OBJECTIVES: Cytotoxic lesions of the corpus callosum (CLOCCs) are secondary lesions associated with entities like infection manifested by restricted diffusion on diffusion-weighted cranial magnetic resonance imaging. Our objectives are to evaluate the clinic-radiological spectrum of pediatric patients with cytotoxic lesions of the corpus callosum (CC). METHODS: Children (0-18 years) admitted between February 2017 and May 2020 with splenial lesions showing diffusion restriction on MRI, either isolated or within involvement of other parts of the brain, were included retrospectively. The primary lesions of the CC (e.g. acute disseminated encephalomyelitis, acute ischemic infarction, and glioblastoma multiforme) were excluded. CLOCCs were divided into infection-associated, metabolic disorder-associated, and trauma-associated lesions, as well as CLOCCs involving other entities. Data were collected from the medical databases. RESULTS: Forty-one patients were determined to have CLOCCs. Twenty-five (61%) were infection-associated, nine (22%) were trauma-associated, and three (7%) were metabolic disorder-associated cases, including 2 inherited disorders of metabolism. There were four (10%) patients with other entities, three with epilepsy, and one had an apparent life-threatening event. Six patients had a known etiology among the infection-associated group; one had multisystem inflammatory syndrome caused by COVID-19 and one had been infected by COVID-19 without any complications. All the infection-associated patients with isolated splenial lesions recovered totally, although six patients required intensive care hospitalization. Four trauma-associated patients had sequela lesions. CONCLUSIONS: CLOCCs are associated with a spectrum of diseases, including the new coronavirus, COVID-19 infection. Infection-associated CLOCCs has the best prognosis, although severe cases may occur. Sequelae are possible based on the etiology.

Percutaneous Endoscopic Gastrostomy Feeding in Children with Cerebral Palsy.

AIM: The prevalence of congenital cerebral palsy (CP) worldwide ranges from 0.15 to 0.4%. CP causes several gastrointestinal complications that inhibit normal eating behavior. This single-center observational study aimed to determine the tolerability and benefits of percutaneous endoscopic gastrostomy (PEG) in pediatric CP patients with malnutrition. MATERIALS AND METHODS: The study included 41 pediatric CP patients with malnutrition. All patient data were retrospectively obtained from Bakirköy Dr. Sadi Konuk Research and Training Hospital, Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Istanbul, Turkey. In addition to baseline measurements of weight, height, triceps skinfold thickness, 1,25-hydroxyvitamin D3, folate, iron, zinc, vitamin B12, hemoglobin, and mean corpuscular volume, data analyzed included follow-up measurements recorded at 3 and 6 months of PEG (standard polymeric enteral supplementation as 1.0 kcal mL-1). RESULTS: There was significant improvement in both height, weight, and triceps skinfold thickness in all patients at 3 and 6 months of PEG (p < 0.05). In terms of blood parameters, there was not significant improvement, except that the number of patients with a low hemoglobin count significantly decreased at 3 and 6 months of (p = 0.022). Moreover, the number of patients with vomiting after PEG also significantly decreased at 3 and 6 months of (p = 0.004). CONCLUSION: PEG significantly improves malnutrition in pediatric CP patients and does not cause any major complications. Based on these findings, we think PEG is a beneficial and cost-effective intervention with a high rate of tolerability in pediatric CP patients with malnutrition.

Axonal Guillain-Barre syndrome associated with SARS-CoV-2 infection in a child.

The relation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and demyelinating Guillain-Barre syndrome (GBS) has been defined. We aim to report the clinical features of a child with axonal GBS associated with SARS-CoV-2. A 6-year-old male presented with symmetric ascending paralysis progressed over a 4-day course and 2 days of fever. He had bilateral lower and upper limb flaccid weakness of 1/5 with absent deep tendon reflexes. He had severe respiratory muscle weakness requiring invasive mechanical ventilation. On admission, SARS-CoV-2 returned as positive by real-time polymerase chain reaction on a nasopharyngeal swab. Cerebrospinal fluid analysis showed elevated protein without pleocytosis. He was diagnosed with GBS associated with SARS-CoV-2 infection. The nerve conduction study was suggestive of acute motor axonal neuropathy. Ten consecutive therapeutic plasma exchange sessions with 5% albumin replacement followed by four sessions on alternate days were performed. On Day 12, methylprednisolone (30 mg/kg/day for 5 days) was given. On Day 18, intravenous immunoglobulin (2 g/kg/day) was given and repeated 14 days after due to severe motor weakness. On Day 60, he was discharged from the hospital with weakness of neck flexor and extensor muscles of 3/5 and the upper limbs and the lower limbs of 2/5 on home-ventilation. Our patient is considered to be the youngest patient presenting with a possible para-infectious association between axonal GBS and SARS-CoV-2 infection. The disease course was severe with a rapid progression, an earlier peak, and prolonged duration in weakness as expected in axonal GBS.

Reversible splenial lesion syndrome associated with SARS-CoV-2 infection in two children.

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral infections. CASE PRESENTATION: We report two children with multisystem inflammatory syndrome-children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed RESLES during the disease course. Encephalopathy was the main central nervous system symptom. Both of the children showed a rapid recovery, and brain magnetic resonance imaging revealed complete resolution of the splenial lesion within 1 week. CONCLUSION: The complete resolution of the splenial lesion and rapid recovery from encephalopathy in RESLES associated with SARS CoV-2 were similar to observed in MERS.

Clinically isolated syndrome and multiple sclerosis in children: a single center study.

BACKGROUND AND OBJECTIVES: This study was conducted to determine the differences in clinical and radiological features at the first demyelinating event in children with clinically isolated syndrome (CIS) and multiple sclerosis (MS). METHODS: This was a single center retrospective cohort study of the children with CIS followed-up at Istanbul University Faculty of Medicine, Department of Pediatric Neurology, between 2010 and 2018. Children with CIS who were assessed at 3, 6, 12 and 24 months following their first identified demyelinating event were included. Demographic data, mode of presentation and the presence of the oligoclonal band in the cerebrospinal fluid (CSF) were abstracted from the medical records. Magnetic resonance imaging of the brain and spinal cord was analyzed for the location, number, size and gadolinium enhancement of the lesions. RESULTS: A total of 51 patients` data was assessed, 38 patients at a mean age of 12.3 years were enrolled in the study. Twenty-seven children (71%) evolved into clinically definite MS after a mean follow-up of 11 months. Older age at first demyelinating event and the presence of the oligoclonal band in CSF were tended to be more common in patients with MS than patients with CIS (p < 0.05). The increased number of T2-hyperintense lesion and the presence of the lesion in periventricular, infratentorial and corpus callosum were associated with a tendency for development of MS (p < 0.05). CONCLUSION: Older age at first demyelinating event, the presence of the oligoclonal band in CSF, the number and localization of T2-hyperintense lesion were associated with a tendency for development of MS.

The factors relevant to partial remission in children with type 1 diabetes mellitus after measles vaccination: A retrospective study.

We aimed to identify the determinants of partial remission in patients with type 1 diabetes mellitus (DM), and whether there is an influence of vaccination against measles on partial remission. This was a retrospective study consisting of consecutive patients diagnosed with type 1 DM followed-up from 1 September 2010, through 30 November 2011. The study included children vaccinated within 3 months after diagnosis, and children unvaccinated during the first 12 months of the disease. The daily insulin dose, hemoglobin A1c, and C-peptide levels, and whether children are in partial remission based on the insulin dose-adjusted HbA1c were recorded at diagnosis and 3, 6, 9, 12, 24, and 36 months. A total of 55 children with type 1 DM were analyzed. Thirty-one patients (56.4%) reached partial remission during the follow-up period, whereas 24 of them did not. Patients with diabetic ketoacidosis (DKA) at diagnosis were less likely to reach partial remission than patients without DKA (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.062-0.946; P = .038). Patients vaccinated against measles were more likely to be in partial remission than patients unvaccinated (OR, 4.2; 95% CI, 1.35-13; P = .011). Partial remission was significantly associated with the C-peptide level and insulin dosage at diagnosis P = .002; P = .013, respectively). The lack of DKA, higher C-peptide level, and lower insulin dosage at diagnosis, and vaccination against measles after diagnosis may have an influence on partial clinical remission in patients with new-onset type 1 DM.

Epileptic spasm and other forms of epilepsy in presumed perinatal arterial ischemic stroke in Turkey after more than 10 years follow-up: A single centre study.

PURPOSE: To identify the frequency of epilepsy and whether the association of epilepsy with clinical and neuroimaging findings in children with presumed perinatal arterial ischemic stroke (PPAIS). METHODS: We performed a retrospective analysis of 37 children with PPAIS followed-up at a tertiary referral center between January 1, 2000, and October 31, 2016. Clinical data including demographic features, age at onset of symptoms and seizures, initial clinical presentation, epilepsy features, used antiepileptic drugs, and thrombophilia screening results were abstracted from medical records. Brain magnetic resonance imaging scans were assessed for infarct laterality, location and affected brain regions. RESULTS: The median age of the patients was 12 years (range 2-17.9 years) at last assessment. The initial symptom of PPAIS was early hand preference in 33 children (89%) and seizure in 4 children (11%). A total of 20 children (54%) developed epilepsy at a median age of 0.9 years. There were two peaks of epilepsy onset in infancy and adolescence. Fifteen children (41%) had focal epilepsy and 5 children (14%) had epileptic spasms. Twelve out of 20 children (60%) with epilepsy had drug resistant epilepsy. Cortical involvement was a statistically significant predictor of epilepsy (p = 0.021, relative risk 4.4, 95% confidence interval 0.7-27.7). CONCLUSION: More than half of the children with PPAIS suffered from epilepsy during childhood, of whom developed drug resistant epilepsy in majority. Children with cortical lesion may have a higher risk to develop epilepsy.

Autism spectrum disorder and attention-deficit/hyperactivity disorder-related symptoms in benign childhood epilepsy with centrotemporal spikes: A prospective case-control study.

BACKGROUND: Benign childhood epilepsy with centrotemporal spikes (BECTS), one of the most common idiopathic epilepsy syndromes in children, has been associated with neuropsychological problems. PURPOSE: The objective of this study was to investigate the frequency of symptoms related to comorbid neurodevelopmental disorders, the autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children with typical BECTS, and to identify corresponding risk factors. METHODS: Children and adolescents with typical BECTS aged 6-16 years were included in the study period from January 1, 2017, to December 31, 2017. Children with atypical presentations of BECTS, other neurological disorders, and preexisting neuropsychiatric disorders were excluded. The ASD and ADHD were assessed by the Social Communication Questionnaire (SCQ) and the Turgay Diagnostic and Statistical Manual of Mental Disorders - 4th Edition - Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S), respectively. Patients' scores were compared with those of healthy subjects. Correlation analyses were performed to evaluate the association between the age at seizure onset, the total number of seizures and the SCQ and T-DSM-IV-S scores. RESULTS: Fifty-eight children with BECTS and 60 healthy children participated in the study. The total SCQ score, the SCQ reciprocal social interaction score, and the SCQ communication score significantly differed between children with BECTS and the control group (p = 0.001, p < 0.001, p = 0.001, respectively). The total ADHD score was significantly different between patients and controls (p < 0.001). A significant difference was observed between patients and controls in terms of the T-DSM-IV-S hyperactivity-impulsivity score and the T-DSM-IV-S inattention score (p = 0.012, p < 0.001, respectively). The age at seizure onset was significantly correlated with the total SCQ score (p = 0.03). The Spearman's correlation coefficient was 0.352 for the total SCQ score, indicating a positive association between the age at seizure onset and the total SCQ score. CONCLUSION: Children with typical BECTS may have an increased risk of suffering from symptoms of ASD and ADHD. Children with late onset of seizures may be more likely to develop neuropsychological disturbances regarding ASD and ADHD.

Efficacy of Stiripentol and the Clinical Outcome in Dravet Syndrome.

Dravet syndrome is a rare and progressive epileptic encephalopathy of infancy. Stiripentol reduces the seizure frequency in patients with Dravet syndrome. We evaluated the clinical characteristics of patients with Dravet syndrome and their response to stiripentol. We retrospectively collected the data of 21 patients (11 females; mean age, 8.2 years, range: 5.4-15 years) with Dravet syndrome who were treated with stiripentol in our outpatient clinic between June 2016 and June 2017. Patients with seizure reduction ≥50% were considered responders. Most of our patients had severe (47%) or moderate (33%) cognitive disabilities, although 14% had mild cognitive disability. There was a significant difference in both status epilepticus and age between the groups with normal/mild versus severe/moderate neurocognitive prognoses. Of the patients, 85.7% were using stiripentol. The mean duration of stiripentol use was 41.2 months (range: 24-64 months). In 12 patients (57%), the seizure frequency decreased by more than 50%, and 2 of them were seizure-free. Status epilepticus was not recorded after stiripentol treatment in 8 of 11 patients with status epilepticus. Despite the small sample size, our results suggest that stiripentol has a favorable efficacy. In addition, considering the absence of status epilepticus after treatment and the negative effects of status epilepticus on cognitive development, early treatment should be initiated in SD patients, for whom disease control is difficult.

Efficacy of rufinamide in childhood refractory epilepsy.

Yildiz EP, Hizli Z, Bektas G, Ulak-Özkan M, Tatli B, Aydinli N, Çaliskan M, Özmen M. Efficacy of rufinamide in childhood refractory epilepsy. Turk J Pediatr 2018; 60: 238-243. Rufinamide has been used as a new antiepileptic drug in the treatment of drug-resistant epilepsy, in recent years. The objective of this study was to evaluate the reliability of rufinamide and its impact on seizure frequency in patients diagnosed with drug-resistant epilepsy, where seizures could not be controlled with `classical` antiepileptic drugs. We retrospectively reviewed the data of epileptic patients who were followed up between January 2004 and December 2014 in the Pediatric Neurology Department. Patients who were diagnosed with `drug resistant epilepsy` and treated with rufinamide were evaluated. Decrease in seizure frequency and drug side effects were assessed as parameters. A total of 38 patients (14 girls, 24 boys) with a mean age of 8.5 (range, 3.5-17) years were included in the study. The mean follow-up duration was 25.5 (23-29.5) months, while the mean maximal dose of rufinamide was 32.5 (28-42) mg/kg/day. Response to treatment was assessed by the reduction in frequency of seizures. The decrease was < 50% (essentially unresponsive to treatment) in 20 patients and 50­99% in 8 patients. Ten patients (26.3%) remained seizure-free. The response rate for tonic seizures was 50%. In drop/attacks seizures, this ratio was found as 73%, which was quite high. Patients with myoclonic and tonic-clonic seizures did not significantly benefit from rufinamide. The rate of patients with Lennox-Gestaut syndrome (LGS) who responded very well (reduction in seizure frequency > 50%) was 55.5%. In the LGS group, patients with drop/attacks showed the best response to treatment. Rufinamide was not effective in two patients diagnosed with Dravet syndrome. Rufinamide can be safely used in pediatric patients who use multiple antiepileptic drugs and are unresponsive to the treatment. It was seen to be effective especially in patients diagnosed with LGS and drop/attacks types of seizures.

Vanishing white matter disease with a novel EIF2B5 mutation: A 10-year follow-up.

BACKGROUND: Vanishing white matter disease is a heterogeneous disorder caused by mutation in one of the five genes encoding subunits of the eukaryotic initiation factor eIF2B. It is a heterogeneous disorder due to phenotypic variation and a clear genotype-phenotype correlation could not be established so far. We describe a novel mutation in the EIF2B5 gene by analyzing the clinical phenotype and the progression of brain lesions for 10 years. CASE: A novel mutation in the EIF2B5 gene was detected in the heterozygous state; c.1688G > A (p. Arg563Gln) mutation in exon 12, accompanied by a previously detected c.806G > A (p. Arg269Gln) mutation in exon 6, leading to substitution of arginine for a glutamine. This compound heterozygous mutation was associated with disease onset at early childhood and relatively slow progression of neurological deterioration. In contrast to previous findings indicated the association of c.806G > A mutation and peripheral neuropathy in patients with vanishing white matter disease, electromyography of our case was normal. The corpus callosum inner rim was the affected area at early stages, which may be remarkable for early diagnosis of vanishing white matter disease. Serial follow-up magnetic resonance imaging revealed the white matter signal abnormality, subsequently cystic degeneration and decrease in white matter volume. CONCLUSION: The novel mutation c.1688G > A in compound heterozygous state leads to intermediate phenotype of the vanishing white matter disease. In the early stages of the disease the signal abnormality in the corpus callosum inner rim might be remarkable.

Spinal muscular atrophy with progressive myoclonic epilepsy linked to mutations in ASAH1.

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), a rare disorder caused by mutation in the ASAH1 gene, is characterized by progressive muscle weakness and intractable epilepsy. The literature about SMA-PME is very rare and most of the time limited to case reports. Mutation in the ASAH1 gene is also found in another rare syndrome which is Farber disease. We report a case of a 13.5-year-old girl with SMA-PME associated with ASAH1 gene mutation. She presented with progressive muscle weakness, tremor, seizure, and cognitive impairment. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epilepsy. The marked difference in disease manifestations may explain why Farber and SMA-PME diseases were not suspected of being allelic conditions. SMA-PME cases with ASAH1 mutation could be treated using therapeutic studies regarding Farber disease. In patients with undefined PME or lower motor neuron disease cases, ASAH1 mutation scans should be studied.