Ictal vocalizations are relatively common in myoclonic-atonic seizures associated with Doose syndrome: an audio-video-polygraphic analysis.

The aim of this study was to investigate ictal vocalizations associated with myoclonic (MS) and myoclonic-atonic seizures (MAS) in patients with myoclonic epilepsy in infants (MEI) and epilepsy with myoclonic-atonic seizures (EMAS, Doose syndrome), respectively. Subjects were retrospectively recruited among patients with MEI and EMAS for whom ictal video-polygraphs were recorded between 1990 and 2019. We reviewed all MS and MAS in order to estimate how often they were associated with vocalizations, and analyze the temporal relationship between vocalizations and spike-wave complexes (SWCs) and myoclonic EMG potentials based on simultaneous examination of the polygraphs and sound signals. Ictal video-polygraphs from 15 patients with MEI (2-34 MS per patient) and 26 with EMAS (2-26 MAS per patient) were examined. Ictal vocalizations were audible in two patients with MEI (11%; 3-18 MS per patient) and nine with EMAS (35%; 2-11 MAS per patient). Sounds were always non-speech and were immediately followed by head or body dropping in the case of MAS. Detailed analysis based on simultaneous and synchronous examination of video-polygraphs and sound signals in one patient with MEI and five patients with EMAS demonstrated that the onset of the ictal vocalizations corresponded to that of the myoclonic EMG potentials and negative spike components of SWC. Comparison of the length of myoclonic EMG potentials as well as the strength of drop seizures between MAS with and without vocalizations revealed that MAS with vocalizations were associated with longer myoclonic EMG potentials and stronger drop seizures than MAS without vocalizations (p<0.05), suggesting that the vocalizations result from strong contraction of axial muscles. Ictal vocalizations due to massive motor seizure activity are a relatively common finding in MAS in Doose syndrome, which may help in the differential diagnosis of epileptic drop attacks.

Morphometric analysis of spike-wave complexes (SWCs) causing myoclonic seizures in children with idiopathic myoclonic epilepsies - A positive SWC component correlates with myoclonic intensity.

AIM: To elucidate the morphological characteristics of spike-wave complexes (SWCs) causing myoclonic seizures (MS) in childhood-onset idiopathic myoclonic epilepsies. SUBJECTS AND METHODS: The subjects were 8 patients, including 4 with epilepsy with myoclonic-atonic seizures (EMAS), 3 with myoclonic epilepsy in infancy (MEI) and 1 with idiopathic unclassifiable myoclonic epilepsy. Morphometric parameters of the SWCs were compared between those with MS [SWC-MS (+)] and those without MS [SWC-MS (-)], and a correlation coefficient analysis was performed between the SWC parameters and the duration of myoclonic electromyogram (EMG) potentials. RESULTS: A total of 155 SWC-MS (+) (range: 7 ∼ 34) and 80 SWC-MS (-) (10 each as a control) were analyzed. Comparison of the parameters of the SWCs between SWC-MS (+) and SWC-MS (-) demonstrated that the depth and the width of the positive-sharp-components (PSC) in the SWC-MS (+) were significantly deeper in amplitude and longer in duration than those in the SWC-MS (-), respectively, in all 8 patients (P < 0.05), whereas the number of the polyphasic-multiple-spike-components (PMSC) and the height of negative-spike-components (NSC) were not significantly different in most of the patients, respectively. The depth and the width of PSC were also significantly correlated with the duration of myoclonic EMG potentials in all patients except one [depth of PSC (n = 7): r = 0.623 ∼ 0.888; width of PSC (n = 8): r = 0.676 ∼ 0.948, P < 0.05]. CONCLUSIONS: This study revealed that the depth and width of PSC of the SWC are positively correlated with the MS intensity in childhood-onset idiopathic myoclonic epilepsies and are an important neurophysiological marker to generate MS.

Transition from pediatric to adult care in a Japanese cohort of childhood-onset epilepsy: prevalence of epileptic syndromes and complexity in the transition.

AIM: We retrospectively examined patients with childhood-onset epilepsy who transitioned from pediatric to adult care to reveal the clinical characteristics and evaluate the complexity of transitioning. METHODS: The subjects were 220 patients (89 males, 131 females) who had been treated at our pediatric epilepsy clinic and had transferred to adult care between 2014 and 2018 without attending a transition clinic or program. The demographic data of the patients were retrospectively analyzed. RESULTS: The ages at transition ranged from 15 to 54 years (median: 27 years old). There were 91 patients with focal epilepsies (FEs) and 129 patients with generalized epilepsies [genetic generalized epilepsy (GGE) n = 30, generalized epilepsy of various etiologies (GEv) n = 99]. A most frequent epileptic syndrome was temporal lobe epilepsy followed by frontal lobe epilepsy in FEs, GTCS only followed by juvenile myoclonic epilepsy in GGE and Lennox-Gastaut syndrome followed by Dravet syndrome in GEv. At the age of transition, a total of 77 of the 96 patients with developmental and epileptic encephalopathies (DEE) had pharmacoresistant seizures, which was positively correlated with a late transition age (P≤0.05). More than monthly seizures and greater than moderate disabilities were noted in 45% and 55% of the patients, respectively. CONCLUSION: The patients with childhood-onset epilepsy transitioned to adult care from the hospital-based pediatric epilepsy clinic were characterized by generalized>focal epilepsy, a frequent complication of DEE, more than monthly seizures, and worse than moderate intellectual disabilities. The complication of DEE made a smooth transition difficult and delayed the transition age.

Unexpected elevation in valproic acid concentration and agranulocytosis in a patient with short-chain acyl-CoA dehydrogenase deficiency.

BACKGROUND: Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive metabolic disorder or condition of fatty acid ß-oxidation, caused by mutations in the gene encoding SCAD (ACADS). We report an infant with SCAD deficiency who unexpectedly exhibited an extremely high blood concentration of valproic acid (VPA) and agranulocytosis. CASE REPORT: An 8-month-old girl was diagnosed with West syndrome (infantile spasms), and VPA was administered at the standard level of 25 mg/kg/day. However, the blood concentration of VPA rose unexpectedly to 230 µg/mL (two- to three-fold higher than the expected value), and continued to remain relatively high even after the dosage was reduced (7 mg/kg/day, blood concentration of 88 µg/mL). Furthermore, she presented with a high-grade fever with agranulocytosis (neutrophil 231/µL). The abnormal pharmacokinetics and toxicity of VPA raised the suspicion of possible inborn errors of metabolism in the fatty acid ß-oxidation pathway. Blood tandem mass spectrometry revealed a transient elevation of C4, and urine gas chromatography-mass spectrometry revealed a continuous elevation of ethylmalonate. Finally, gene analysis revealed compound heterozygous mutations, c.625G > A (p.G209S) and c.1031A > G (p.E344G), in ACADS. CONCLUSION: VPA should be avoided if a patient is suspected to have inborn errors of ß-oxidation including SCAD deficiency.

Low-dose phenobarbital for epilepsy with myoclonic absences: A case report.

BACKGROUND: Epilepsy with myoclonic absences (EMA) is a rare childhood-onset syndrome characterized by absences of responsiveness accompanied by bilateral rhythmic clonic-like myoclonic jerks. Herein, we describe the case of a child with EMA, resistant to multiple commonly used antiepileptic drugs, in whom low-dose phenobarbital unexpectedly achieved complete remission of epilepsy. CASE REPORT: A 10-year-old boy was referred to our hospital because of pharmaco-resistant frequent myoclonic absence seizures (MASs) and occasional generalized tonic-clonic seizures (GTCSs) that had commenced at the age of 7 years. Antiepileptic drugs including valproate sodium (VPA), levetiracetam, ethosuximide (ESM), clobazam, zonisamide, topiramate, clonazepam and lamotrigine were tested without significant effects. At the age of 8 years, phenobarbital was added to the VPA and ESM and increased to 1.2 mg/kg/day (blood concentration 8.6 µg/mL), which suppressed MASs completely within 1 month, and epileptic discharges on electroencephalography (EEG) within 5 months. To date, the boy has been seizure-free with normal EEG for 2 years. CONCLUSION: Phenobarbital is a potential therapeutic option for pharmaco-resistant EMA.

A de novo GABRB2 variant associated with myoclonic status epilepticus and rhythmic high-amplitude delta with superimposed (poly) spikes (RHADS).

We report a child who developed myoclonic status epilepticus (MSE) at four months of age, associated with rhythmic high-amplitude delta and superimposed (poly) spikes (RHADS), harbouring a GABRB2 (ß2 subunit of the GABA A receptor) variant. The patient was treated under a presumptive diagnosis of neonatal-onset Alpers syndrome (AS) and underwent targeted sequence analysis for POLG1 (polymerase gamma 1) and subsequent whole-exome sequence analysis (WES). The patient is currently a 10-year, eight-month-old boy, suffering from daily MSE associated with RHADS and severe global developmental delay from early infancy. Although POLG1 mutation was negative, WES revealed a de novo missense variant of GABRB2 (NM_021911.2: c.784G>T, p.[Val262Phe]). Based on a review of case series with GABRB2 variants, we found that five of the 18 cases shared the clinical and EEG characteristics associated with our patient. In summary, this de novo GABRB2 variant was associated with an AS phenotype, characterized by treatment-resistant MSE and RHADS, and may represent an alternative aetiology for neonatal-onset AS without POLG1 mutation [Published with video sequence].

A missense variant of SMC1A causes periodic pharmaco-resistant cluster seizures similar to PCDH19-related epilepsy.

SMC1A variants causing Cornelia de Lange syndrome (CdLS) produce another phenotype characterized by moderate to severe neurological impairment and severe early-onset epilepsy without morphological characteristics of CdLS. The patients are all female and have truncation mutations in SMC1A. The epilepsy also follows a characteristic clinical course with pharmaco-resistant cluster seizures since infancy, mimicking that of PCDH19-related epilepsy. We report here that a missense variant of the SMC1A gene affecting a daughter (proband) and her mother caused similar phenotypes of early-onset (2 years and 1 month of age) and late-onset (12 years of age) epilepsy, respectively. Both patients lacked the morphological characteristics of CdLS, and had severe and moderate intellectual disability, respectively. The cluster seizures were characteristic, occurring approximately every 2-4 weeks (interval; mean ±â€¯SD: 20.2 ±â€¯8.3 days) at the peak of the clinical course, especially in the proband. Thus, SMC1A-related encephalopathy is caused not only by truncation mutations but also by missense variants of the SMC1A gene. The periodicity of cluster seizures mimicking that of PCDH19-related epilepsy may characterize SMC1A-related encephalopathy.

An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a patient with a novel frameshift mutation in HNRNPU.

Microdeletions in the 1q44 region encompassing the HNRNPU gene have been associated with infantile spasms and hemiconvulsion-hemiplegia-epilepsy syndrome. Recent studies have revealed that heterozygous HNRNPU variants resulted in early onset epilepsy and severe intellectual disability. A de novo frameshift mutation in HNRNPU was identified in a 5-year-old boy with developmental delay associated with Rett-like features including stereotypic hand movements and respiratory abnormalities with episode of apnea and hyperpnea followed by falling. He also showed an episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy. Unique and variable clinical features are related to loss-of-function or haploinsufficiency of HNRNPU.

Thrombocytopenia associated with Mycoplasma pneumonia during pregnancy: case presentation and approach for differential diagnosis.

Thrombocytopenia during pregnancy has many different causes, but Mycoplasma pneumoniae is not usually considered one of the several pathogens that induce thrombocytopenia. Herein, we present a case of severe thrombocytopenia that was associated with M. pneumoniae during pregnancy. The patient experienced fever, cough, and cytopenia with M. pneumoniae-specific IgM antibody increasing from 40-fold to 160-fold during the 2 weeks of illness. A diagnosis was made after excluding other diseases that cause thrombocytopenia. The patient was successfully treated with azithromycin hydrate, and she delivered a healthy newborn without any complications. Pregnant women who are infected with M. pneumoniae during pregnancy may develop severe and fatal thrombocytopenia. Prompt diagnosis and initiation of treatment lead to early recovery.

Ketogenic diet therapy can improve ACTH-resistant West syndrome in Japan.

PURPOSE: Ketogenic diet therapy (KD) has been used to treat children with refractory generalized epilepsy. We herein reported the efficacy of KD for West syndrome (WS) resistant to ACTH therapy. SUBJECTS: SUBJECTS, consisting of 6 patients (3 boys, 3 girls) with WS who continued to have epileptic spasms (ES) and hypsarrhythmia, received KD because other treatments including ACTH therapy failed to control WS. METHODS: We retrospectively studied the clinical details of these patients and the efficacy of KD. RESULTS: The mean age at the onset of epilepsy was 4 months (0-15 months). The underlying etiology consisted of lissencephaly, Down's syndrome, and focal cortical dysplasia. Hypsarrhythmia disappeared 1 month after the introduction of KD in 5 patients. The disappearance of ES was achieved in 2 patients, the frequency of ES episodes was 80% less in 3, and no change was observed in 1. Psychomotor development was promoted in 5 patients, along with improvements in ES and EEG. Gastrointestinal complications and lethargy, presumably caused by rapid ketosis, were reported as side effects in 3 patients during the first week of KD. Side effects including lethargy, anorexia, and unfavorable weight gain continued thereafter in these patients in spite of tolerance to KD. CONCLUSION: KD was effective for WS resistant to ACTH therapy, although gastrointestinal side effects should be considered when introducing KD to milk-fed infants.

Latent hypoparathyroidism in an osteoporotic patient with multiple endocrinopathies and secondary hemochromatosis due to multiple blood transfusions, unmasked by alendronate and glucocorticoid at adrenal crisis.

A 30-year-old normocalcemic man with hypopituitarism, hypogonadism, diabetes mellitus, and secondary hemochromatosis due to multiple blood transfusions was admitted because of adrenal crisis. After intravenous administration of saline and cortisol, the corrected serum level of calcium decreased to 7.3 mg/dl. This osteoporotic patient had been prescribed alendronate for radial bone fracture. Since the increase in intact PTH (68 pg/ml) was impaired compared to that seen in hypocalcemic patients with secondary hyperparathyroidism, we presume that the patient has had latent hypoparathyroidism, which was unmasked by the administration of glucocorticoid and bisphosphonate. With a supplemented dose of 1alpha-OHD3, the patient has been eucalcemic.