Hiroyuki Wakamoto

Subclinical portal-systemic encephalopathy in a child with congenital absence of the portal vein.

A 6-year-old girl with congenital absence of the portal vein (CAPV) who had persistent hyperammonemia due to a congenital portosystemic shunt is reported. The patient only exhibited mild intention tremor, without any apparent neurological manifestations of portal-systemic encephalopathy. However, magnetic resonance imaging of the head showed white matter atrophy with ventricular dilatation, which is thought to represent subclinical brain damage caused by chronic hyperammonemia. This is the first report of subclinical portal-systemic encephalopathy in a patient with CAPV. The present case suggests that the effect of a congenital portosystemic shunt on the central nervous system is serious, but can be clinically latent in children with CAPV.

Alpha-Methyl-l-Tryptophan Positron Emission Tomography in Epilepsy With Cortical Developmental Malformations

Preliminary studies suggest that alpha[(11)C]methyl-l-tryptophan positron emission tomography can detect the epileptic focus within malformations of cortical development. We determined the sensitivity and specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying epileptic focus in children with intractable, neocortical epilepsy with and without malformations of cortical development. Seventy-three epileptic children were classified into lesional and nonlesional groups, and compared regarding focal increased alpha-[(11)C]methyl-l-tryptophan uptake. The sensitivity and specificity of focal increased alpha-[(11)C]methyl-l-tryptophan uptake, using intracranial electroencephalogram localization of seizure onset as the standard, were compared between lesional and nonlesional groups. The specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography for detecting seizure onset lobe was equally high in lesional (97%) and nonlesional groups (100%), whereas sensitivity was higher in the lesional than the nonlesional group (47% versus 29%; P = 0.047). The incidence of alpha-[(11)C]methyl-l-tryptophan uptake abnormality was higher in the lesional than the nonlesional group (P < 0.01). Alpha-[(11)C]methyl-l-tryptophan positron emission tomography localized and visualized epileptogenic regions in 25% of patients with nonlocalizing magnetic resonance imaging. Although overall sensitivity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying neocortical epileptic focus is modest, specificity is extremely high. When an alpha-[(11)C]methyl-l-tryptophan focus is detected, it likely represents the epileptogenic region to be resected.

The Spectrum of ZEB2 Mutations Causing the Mowat-Wilson Syndrome in Japanese Populations

Mowat–Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by moderate or severe intellectual disability, a characteristic facial appearance, microcephaly, epilepsy, agenesis or hypoplasia of the corpus callosum, congenital heart defects, Hirschsprung disease, and urogenital/renal anomalies. It is caused by de novo heterozygous loss of function mutations including nonsense mutations, frameshift mutations, and deletions in ZEB2 at 2q22. ZEB2 encodes the zinc finger E‐box binding homeobox 2 protein consisting of 1,214 amino acids. Herein, we report 13 nonsense and 27 frameshift mutations from 40 newly identified MWS patients in Japan. Although the clinical findings of all the Japanese MWS patients with nonsense and frameshift mutations were quite similar to the previous review reports of MWS caused by nonsense mutations, frameshift mutations and deletions of ZEB2, the frequencies of microcephaly, Hirschsprung disease, and urogenital/renal anomalies were small. Patients harbored mutations spanning the region between the amino acids 55 and 1,204 in wild‐type ZEB2. There was no obvious genotype–phenotype correlation among the patients. A transfection study demonstrated that the cellular level of the longest form of the mutant ZEB2 protein harboring the p.D1204Rfs*29 mutation was remarkably low. The results showed that the 3′‐end frameshift mutation of ZEB2 causes MWS due to ZEB2 instability.

Diffusion tensor imaging of the corticospinal tract following cerebral hemispherectomy.

Following cerebral hemispherectomy, the corticospinal tract is believed to undergo reorganizational changes, which can induce enhanced function of the contralateral motor pathway and mediate partial recovery of motor function. The aim of this study was to use diffusion tensor imaging to investigate the effects of hemispherectomy on the corticospinal tract, with particular attention to the corticospinal tract contralateral to the resection. Diffusion tensor imaging would presumably detect microstructural abnormalities through quantitative measurements of the fiber tract integrity and orientation. Four patients with anatomic hemispherectomy and three patients with subtotal hemispherectomy were examined and compared with age-matched normal controls. Apparent diffusion coefficient and fractional anisotropy values were measured in regions along the corticospinal tract: internal capsule, cerebral peduncle, rostral pons, midpons, and caudal pons. None of the patients with anatomic hemispherectomy or subtotal hemispherectomy showed significant changes in either apparent diffusion coefficient or fractional anisotropy values in the corticospinal tract contralateral to the resected hemisphere, whereas increased apparent diffusion coefficient and decreased fractional anisotropy were observed in the ipsilateral rostral pons, midpons, and caudal pons of all patients with anatomic hemispherectomy, as well as in the ipsilateral cerebral peduncle of one patient with subtotal hemispherectomy. Increased apparent diffusion coefficient values were also noted in the ipsilateral internal capsule of the same patient. This study revealed no evidence of significant reinforcement of the contralateral corticospinal tract in patients with hemispherectomy, at least from diffusion tensor imaging measurements, but suggests that wallerian degeneration most likely occurs in the ipsilateral motor pathway. (J Child Neurol 2006;21:566—571; DOI 10.2310/7010.2006.00150).

SPECT in focal enterovirus encephalitis: evidence for local cerebral vasculitis

We report a 4-year-old, left-handed male with focal coxsackievirus A3 encephalitis who presented with seizures and acquired aphasia. Electroencephalography exhibited focal spike discharges over the right frontal regions, but cranial magnetic resonance imaging did not reveal any structural abnormalities. However, brain single-photon emission computed tomography performed during the acute phase disclosed focal hypoperfusion in the right frontal lobe, consistent with decreased regional cerebral blood flow in the territory of some branches of the right cerebral anterior artery. Without specific treatment, the patient recovered completely within 1 month, when brain single-photon emission computed tomography images returned to normal and cranial magnetic resonance imaging still demonstrated no abnormalities. The present case suggests the possible role of transient local cerebral vasculitis in the pathogenesis of focal enterovirus encephalitis.

Idiopathic small-fiber sensory neuropathy in childhood: A diagnosis based on objective findings on punch skin biopsy specimens

Idiopathic small-fiber sensory neuropathy (SFSN) has not previously been reported in children. Although affected patients complain of neuropathic pain, this condition is often difficult to diagnose because of the few objective physical signs and normal nerve conduction studies. We report a girl with idiopathic SFSN in whom the results of a sural nerve biopsy were normal, but punch skin biopsy revealed reduced intraepidermal nerve fiber density and established the diagnosis. Idiopathic SFSN should be considered in the differential diagnosis of children who have burning limb pain with no routine electrophysiologic or pathologic abnormalities.

Elevated Pitch Perception Owing to Carbamazepine-Activating Effect on the Peripheral Auditory System: Auditory Brainstem Response Study

Auditory disturbance is an uncommon side effect of carbamazepine, the pathophysiologic mechanism of which has not been clearly elucidated. We performed an auditory brainstem response study in a 9-year-old boy with epilepsy who had suffered from falsely higher pitch perception immediately after the start of carbamazepine treatment. The auditory brainstem response results showed that both the peak latency of wave V and the interpeak latencies of waves I to V were significantly prolonged with 85 dB HL click stimulation and that the peak amplitudes of the waves were noticeably elevated, particularly with lower click stimulation intensity. Although it has been shown that carbamazepine has a suppressive effect on the central nervous system, these auditory brainstem response findings might constitute evidence of a carbamazepine-activating effect on the peripheral auditory system, which probably increased the sensitivity to low-pitched sounds, causing the development of falsely higher pitch perception in our patient. (J Child Neurol 2004; 19:453-455).

An immunologic case study of acute encephalitis with refractory, repetitive partial seizures

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is a neurologic syndrome characterized by extraordinarily frequent and refractory partial seizures, which immediately evolve into refractory epilepsy. To elucidate the pathophysiology of AERRPS, we performed an immunologic study of an affected boy, revealing decreased natural killer (NK) cell activity in the peripheral blood mononuclear cells. IgG antibodies against the glutamate receptor (GluR)ε2, ζ1, and δ2 subunits were all positive in both the serum and cerebrospinal fluid (CSF). There were raised plasma concentrations of interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ as well as an extremely elevated CSF level of IL-6. These findings suggest that AERRPS is immune-mediated encephalitis, in which both autoimmunity and exaggerated cytokine production are involved. NK cell dysfunction may be the underlying abnormality in this AERRPS case, which might have contributed to the production of GluR autoantibodies.

Clinical investigation of genetic contributions to childhood-onset epilepsies and epileptic syndromes

Although there have been major advances in the understanding of the molecular bases of certain inherited epilepsy syndromes, clinical studies are still needed to verify the possible genetic contributions to common epilepsies. We examined the proportions of positive family histories of epilepsy (within second-degree relatives) and consanguinity (within first-degree relatives) in 311 probands with childhood-onset epilepsy, and found that they had high family history rates of epilepsy (19.3%) and consanguinity (6.1%). A positive family history of epilepsy was found more in probands with generalized epilepsy than in ones with localization-related epilepsy, and more in probands with idiopathic/cryptogenic epilepsy than in ones with symptomatic epilepsy. However, on analysis after the symptomatic epilepsies had been divided into two categories, probands with pre- or perinatal symptomatic generalized epilepsy and ones with postnatal symptomatic localization-related epilepsy showed high positive family history rates, similar to ones with idiopathic/cryptogenic epilepsy. On the other hand, a positive family history of consanguinity was noted more in probands with generalized epilepsy than in ones with localization-related epilepsy, but there was no significant difference between probands with idiopathic/cryptogenic epilepsy and ones with symptomatic epilepsy. These findings suggest that in addition to the hereditary effect on idiopathic/cryptogenic epilepsy, a genetic susceptibility may contribute to the development of pre- or perinatal symptomatic generalized epilepsy, and to that of postnatal symptomatic localization-related epilepsy. Furthermore, a genetic predisposition seems to have an influence through consanguinity on the etiologies of both idiopathic/cryptogenic and symptomatic generalized epilepsies.

Leukophagocytosis in human parvovirus B19-induced transient bicytopenia in a healthy child

A previously healthy 11 year old boy had transient leukopenia and thrombocytopenia associated with human parvovirus B19 (B19) infection. This case suggested that low‐grade hemophagocytosis can be involved in developing B19‐related cytopenia even in an otherwise healthy child. Bone marrow aspiration at an early stage could reveal the underlying mechanism of B19‐related cytopenia.