Perivascular abnormalities in pediatric encephalopathy with fulminant brain edema.

BACKGROUND: Acute encephalopathy with acute brain swelling (ABS) is a recently proposed disease of unknown etiology, characterized by rapid progression to whole-brain swelling. To our knowledge, we reported the first case of a patient with acute encephalopathy with ABS wherein brain magnetic resonance imaging (MRI) abnormalities were noted prior to the diffuse brain swelling onset. CASE PRESENTATION: An 11-year-old boy was admitted to our unit owing to prolonged disturbance of consciousness following febrile status epilepticus. At the initial visit, the vital signs were within the normal range, except for the body temperature and consciousness level (Glasgow Coma Scale 6; E1V1M4). The initial laboratory results showed elevated inflammatory marker levels and mild hyponatremia. Cerebrospinal fluid analysis revealed albuminocytologic dissociation, whereas the myelin basic protein level was not elevated. Electroencephalography showed diffuse, high-amplitude slow waves. No abnormalities were detected on the initial brain computed tomography (CT) scan. However, at 11 h after the seizure onset, diffuse hyperintense lesions were observed throughout the cerebrum on T2-weighted brain MRI. The patient was diagnosed with acute encephalopathy and received methylprednisolone-pulse therapy (1 g) with high-dose gamma globulin (1 g/kg) administration. At 14 h after the seizure onset, the patient was declared brain-dead; the brain CT findings revealed whole-brain swelling and herniation. CONCLUSION: Our findings were suggestive of a perivascular pathophysiology and may be used for subtyping acute encephalopathy. In cases where such findings are observed, subsequent development of severe diffuse brain swelling should be considered.

Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency.

Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy. Nerve conduction studies revealed both axonal degeneration and demyelinating features. A diagnosis of cerebral folate deficiency was confirmed by a homozygous c.466T>G (p.W156G) mutation in FOLR1, coupled with extremely low cerebrospinal fluid levels of 5-methyltetrahydrofolate. Her symptoms, neuroradiological findings, and polyneuropathy were alleviated by oral folinic acid treatment in conjunction with intravenous and intramuscular administration therapy. Our patient shows that folinic acid therapy can ameliorate the clinical symptoms, white matter disturbances, cortical insults, and peripheral neuropathy of cerebral folate deficiency caused by FOLR1 mutation. It is important to recognize these clinical symptoms and make a precise diagnosis early on, because cerebral folate deficiency is treatable.

High prevalence of genetic alterations in early-onset epileptic encephalopathies associated with infantile movement disorders.

OBJECTIVE: Recent studies have elucidated causative roles for genetic abnormalities in early-onset epileptic encephalopathies (EOEE). Accompanying characteristic features, in addition to seizures, have also been suggested to provide important clues for an early and accurate genetic diagnosis of affected patients. In this study, we investigated the underlying genetic causes in patients with EOEE associated with infantile movement disorders. METHODS: We examined 11 patients with EOEE and involuntary movements (nine with West syndrome and two with nonsyndromic epileptic encephalopathy). All showed severe developmental delay, cognitive impairment, and involuntary movements such as chorea, ballism, dyskinesia or myoclonus, and hand stereotypies. We performed whole-exome sequencing of 10 patients, while the other patient underwent high-resolution melting analysis of candidate EOEE genes. RESULTS: We identified mutations in CDKL5, SCN2A, SETD5, ALG13, and TBL1XR1 in seven patients with West syndrome, and in SCN1A and GRIN1 in the two patients with unclassified epileptic encephalopathy. All mutations were validated as de novo events. The genetic cause was undetermined in the remaining two patients. CONCLUSIONS: We found pathogenic mutations in seven genes, in nine of 11 patients with EOEE and involuntary movements. Although the results of our study are preliminary because of the small number of patients, they nevertheless suggest that specific accompanying phenotypes such as hyperkinetic movements or hand stereotypies could be important in narrowing the disease spectrum and identifying causative genetic abnormalities.

Acute encephalitis and encephalopathy associated with human parvovirus B19 infection in children.

Reports of neurologic manifestations of human parvovirus B19 (B19) infection have been on the rise. Acute encephalitis and encephalopathy is the most common, accounting for 38.8% of total B19-associated neurological manifestations. To date, 34 children with B19 encephalitis and encephalopathy have been reported, which includes 21 encephalitis and 13 encephalopathy cases. Ten (29%) were immunocompromised and 17 (39%) had underlying diseases. Fever at the onset of disease and rash presented in 44.1% and 20.6% of patients, respectively. Neurological manifestations include alteration of consciousness occurred in all patients, seizures in 15 (44.1%) patients, and focal neurologic signs in 12 (35.3%) patients. Anemia and pleocytosis in cerebrospinal fluid (CSF) occurred in 56.3% and 48.1% of patients, respectively. Serum Anti-B19 IgM (82.6%) and CSF B19 DNA (90%) were positive in the majority of cases. Some patients were treated with intravenous immunoglobulins and/or steroids, although an accurate evaluation of the efficacy of these treatment modalities cannot be determined. Nineteen (57.6%) patients recovered completely, 11 (33.3%) patients had some neurological sequelae and 3 (8.8%) patients died. Although the precise pathogenesis underlying the development of B19 encephalitis and encephalopathy is unclear, direct B19 infection or NS1protein of B19 toxicity in the brain, and immune-mediated brain injuries have been proposed.

Rub epilepsy in an infant with Turner syndrome.

We report a case of infantile refractory epilepsy associated with Turner syndrome (TS), showing very frequent, focal clonic seizures of the left upper extremity. Characteristically, in addition to spontaneous fits, her seizure was inducible by rubbing her left hand and forearm for a few seconds. Accordingly, she was diagnosed with a rare form of reflex epilepsy, "rub epilepsy". Neuroradiological investigation indicated the existence of cortical abnormalities, such as focal cortical dysplasia of the right parietal lobe. Patients with TS are reported to have neuroanatomical abnormalities, especially of the parietal lobe. Thus, our case may imply a causal relationship between potential cortical hyperexcitability of the parietal lobe and epilepsy in TS. This is the first reported infantile case of rub epilepsy, and more generally, reflex epilepsy associated with TS.

Gómez-López-Hernández syndrome in a Japanese patient: a case report.

Gómez-López-Hernández syndrome (GLHS) is a rare neurocutaneous syndrome characterized by the triad of rhombencephalosynapsis, trigeminal anesthesia, and bilateral parieto-occipital alopecia. We herein describe the first Japanese patient with GLHS characterized by the standard triad with typical craniofacial anomaly including hypertelorism, brachyturricephaly and midface retrusion, and a short stature. This female patient had also exhibited fever-induced convulsive seizures and psychomotor developmental delay since infancy. Brain magnetic resonance imaging showed severe rhombencephalosynapsis, supratentorial abnormalities (aplasia of the septum pellucidum, severe ventricular enlargement, and hypoplasia of the corpus callosum), and hippocampus atrophy. Bilateral ectopic cerebellums were also observed. This report describes the long-term clinical outcome of GLHS and a new neuroradiological finding regarding rhombencephalosynapsis.

Infantile epileptic encephalopathy with a hyperkinetic movement disorder and hand stereotypies associated with a novel SCN1A mutation.

We report a female patient who presented with intractable epileptic seizures, profound developmental delay since early infancy, and hyperkinetic movements with hand stereotypies. The patient initially developed focal seizures with multiple foci at 3 months of age. Thereafter, the seizures evolved to frequent episodes of hyperthermia-induced status epilepticus. A novel de novo SCN1A mutation was identified by whole-exome sequence analysis. This case demonstrates that SCN1A mutations may cause movement disorders as an atypical phenotype and the case history of this patient may expand our understanding of the clinical spectrum of SCN1A-associated epileptic encephalopathy. [Published with video sequences].