A Pediatric Case of B Cell Precursor ALL With Blinatumomab-associated Encephalopathy.

Blinatumomab is a CD3/CD19-directed bispecific T-cell engager used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Although blinatumomab has shown efficacy, it can cause serious adverse events, including cytokine release syndrome and neurological events. Among the neurological events, encephalopathy is rare, and knowledge is lacking. Herein, we present a pediatric case of blinatumomab-associated encephalopathy that initially presented with refractory convulsions and later developed into a cerebral infarction. The patient experienced prolonged paralysis and increased brain damage.

A Successful Infliximab Treatment of a Pediatric Case of Severe Polyarteritis Nodosa With a Cerebral Infarction and a Decreased Adenosine Deaminase 2 Activity.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis common in males over 50 years of age that causes various organ symptoms. In recent years, it has become important to distinguish deficiency of adenosine deaminase 2 (DADA2) from childhood-onset PAN. A 13-year-old girl was urgently transferred to our hospital with sudden weakness in her right upper and lower limbs. The National Institutes of Health Stroke Scale (NIHSS) was 8. Plain MRI of the brain indicated high-signal areas in the right caudate nucleus, internal capsule, and left basal ganglia when applying T2-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI); and low signals in the same regions in an apparent diffusion coefficient (ADC) map. It demonstrated inflammatory demyelinating disease of the central nervous system or multiple cerebral infarctions attributable to vasculitis, and it is difficult to differentiate between them based on image findings alone, and cannot be determined without following the clinical course. Hence, we treated with steroid therapy, which is effective for both conditions. Although the paralysis was alleviated, an MRI of the brain reperformed on day 7 revealed expansion of the lesion with contrast enhancement in the feeding area of the left lateral striatal artery, a high signal in DWI, and a low signal in an ADC map. Based on the clinical and radiological findings, we diagnosed a cerebral infarction attributable to vasculitis. Contrast computed tomography (CT) of her chest and abdominal CT angiography revealed that she met the diagnostic criteria for PAN, and adenosine deaminase 2 (AD2) activity level was low. The patient was treated with steroids combined with azathioprine and cyclophosphamide but three weeks after discharge developed a new cerebral infarction in the right basal ganglia. We commenced infliximab; no recurrence of cerebral infarction has been noted. The low AD2 activity may explain the intractable atypical course of this case. Further studies are needed to reveal the role of AD2 in patients with residual enzyme activity and reevaluation of the PAN diagnostic criteria is essential.

Evaluation of cerebrospinal fluid biomarkers in pediatric patients with spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterised by muscle weakness and muscle atrophy and classified into five known subtypes based on clinical features. The recent development of novel drugs to treat SMA has been encouraging, and nusinersen is the first drug approved to treat SMA. OBJECTIVE: To explore cerebrospinal fluid (CSF) biomarkers of SMA and investigate their relationship with symptoms and the treatment response in pediatric patients. METHODS: We analyzed the CSF levels of chitotriosidase 1 (CHIT1) and inflammatory cytokines (tumor necrosis factor [TNF]-α and interferon [INF]-γ) using enzyme-linked immunosorbent assays in pediatric SMA patients treated at Hiroshima University Hospital over 2 years. RESULTS: This study analyzed pediatric SMA patients. While the CSF inflammatory cytokines (TNF-α and INF-γ) in these SMA children were unchanged, the CHIT1 levels decreased significantly from year 1 to 2 of treatment. We also found a trend toward an inverse correlation between the motor function score (HINE-2 scores) and CHIT1 level from year 1 to 2 of treatment. CONCLUSIONS: CHIT1 may be a CSF biomarker of the treatment response in pediatric SMA.

Effect of Lacosamide therapy on blood cells and IgA levels in children and adolescents with epilepsy in a clinical setting.

INTRODUCTION: Lacosamide (LCM) is a third-generation antiepileptic drug (AED) that affects sodium channel inactivation. AEDs can affect multiple organ systems and blood parameters. Carbamazepine (CBZ) reportedly affects blood sodium, lipid, and immunoglobulin levels and thyroid function. Despite multiple studies on the adverse effects of AEDs, few reports have discussed the impact of LCM on blood parameters. The purpose of this study was to clarify the effects of LCM on blood parameters. METHODS: We retrospectively examined the medical records of 15 children and adolescents in whom LCM was initiated between April 2017 and March 2021, 6 and 12 months after treatment initiation. Blood cell counts, biochemical and thyroid function, and immunoglobulin levels were investigated at baseline and 6 and 12 months after initiation of LCM. RESULTS: Neutrophil levels were significantly reduced 12 months after LCM initiation (p = 0.0046); however, the value was not abnormal. Immunoglobulin A was significantly elevated 6 and 12 months after LCM initiation (p = 0.0078 and 0.020, respectively). No significant difference was identified in the other parameters. Electrolyte and lipid levels and thyroid function remained unaffected, unlike with CBZ. CONCLUSIONS: LCM may affect the immune system, as well as hematological parameters. Further investigation with larger samples is required in the future to assess the clinical impact.

[A case suspected Sensory Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis].

A 9-year-old girl was admitted to our hospital with severe plantar pain, 7 days after the onset of Campylobacter jejuni enteritis. On admission, extremity strength and the deep tendon reflex were normal; however, there was difficulty in walking owing to plantar pain. Motor nerve conduction test showed no abnormalities. No spinal cord protein cell dissociation. Lumbar spine-enhanced MRI showed a 4th and 5th lumbar vertebrae nerve root contrast-enhanced effect. Gabapentin was effective in minimizing her pain, eventually enabling the patient to walk. Antiganglioside antibody tests on admission showed multiple positive results. Six months after the initial onset of symptoms, she had recovered completely. She was suspected with sensory Guillain-Barré syndrome (GBS). GBS subsequent to Campylobacter jejuni enteritis has been recognized as an acute motor axonal neuropathy; hence, this report is considered to be valuable.

Clinical impact of the dose and blood concentration of lacosamide in Japanese pediatric patients with epilepsy: A cohort study.

PURPOSE: The relationship between treatment efficacy/tolerability and the dose/blood concentration of lacosamide (LCM) was investigated in a clinical cohort of Japanese pediatric patients with epilepsy. METHODS: This retrospective analysis reviewed the medical records of patients treated with LCM for >6 months at the Department of Pediatrics, Hiroshima University Hospital, from September 2017 to January 2021. The collected data included age, sex, epilepsy type, seizure type, seizure frequency before and after treatment initiation, adverse events leading to LCM discontinuation, dose at any evaluation point, serum concentration, and concomitant antiepileptic drugs (AEDs). RESULTS: The study included 51 patients (31 male patients) between the ages of 2 and 19 years. All patients were Japanese. Epilepsy was classified as focal in 44 patients, generalized in six patients, and combined generalized and focal in one patient. The 50% responder rate for LCM treatment was 56.9%. Seven patients experienced complete seizure control (absence of seizures for 6 months before the follow-up visit). A relationship between dose and blood concentration was identified. Although the blood LCM concentration was higher in the responders than in the nonresponders (7.86 vs. 6.16 µg/mL; p = 0.028), there was no significant difference in dose between the two groups. Lacosamide showed efficacy at a dose >5 mg/kg/day in more than half of the 50% responders. The treatment-emergent adverse events (TEAEs) included seizure aggravation in five patients, irritability in two patients, and somnolence and drug eruption in one patient each. In six patients with TEAEs, the TEAEs developed within 1 month after treatment initiation and led to LCM discontinuation. CONCLUSION: In Japanese pediatric patients with epilepsy, LCM treatment is effective, particularly at higher doses. The blood concentration may be related more to efficacy than to dose. Lacosamide is generally well-tolerated by pediatric patients, and should be used at the maximum tolerable dose (needed to be gradually increased) in patients with otherwise insufficient seizure control. As TEAEs leading to discontinue treatment likely occur in early phase, it is needed to monitor patients carefully if TEAEs would happen in that phase.