Toshihide Watanabe

Childhood multiple sclerosis: MR images and clinical variations in four Japanese cases

We report four Japanese cases of multiple sclerosis (MS) starting during childhood. In three of them, onset occurred in the prepubertal period. Case 1 showed a rare clinical condition: the patient presented with Devic disease, and 2 years later she was complicated by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The other three cases had symptoms of gait disturbance, cerebellar signs, weakness of the extremities and impaired visual acuity. Headache was seen in Case 2 and medial longitudinal fasciculus (MLF) syndrome in Case 4. In Cases 2, 3 and 4, diagnoses were conclusively made by T2-weighted magnetic resonance imaging (MRI). MRI, brain stem auditory, visual and somatosensory evoked potentials are extremely useful for evaluating the clinical conditions of children with MS.

Everolimus Treatment for an Early Infantile Subependymal Giant Cell Astrocytoma With Tuberous Sclerosis Complex

Subependymal giant cell astrocytomas are benign tumors often observed with tuberous sclerosis complex. These tumors are rarely diagnosed during fetal life or early infancy. Until recently, the only available treatment has been surgical resection. Current clinical research has demonstrated that everolimus can induce these tumors’ regression. We report a 19-month-old boy with tuberous sclerosis complex. At 2 months of age, he presented with congenital subependymal giant cell astrocytoma that was complicated by refractory epilepsy and severe mental retardation. Treatment with everolimus was started when he was 10 months old. Three months after initiating everolimus, the tumor was significantly reduced in size, and the reduction was subsequently maintained. His seizures decreased and he showed cognitive and developmental improvement. No severe adverse events have been observed to date. Everolimus has promise as an effective alternative to surgery for subependymal giant cell astrocytomas during early infancy.

Compound heterozygous GFM2 mutations with Leigh syndrome complicated by arthrogryposis multiplex congenita.

Defects in the mitochondrial translation apparatus can impair energy production in affected tissues and organs. Most components of this apparatus are encoded by nuclear genes, including GFM2, which encodes a mitochondrial ribosome recycling factor. A few patients with mutations in some of these genes have been reported to date. Here, we present two female siblings with arthrogryposis multiplex congenita, optic atrophy and severe mental retardation. The younger sister had a progressive cerebellar atrophy and bilateral neuropathological findings in the brainstem. Although her cerebrospinal fluid (CSF) levels of lactate and pyruvate were not increased, brain magnetic resonance spectroscopy showed a lactate peak. Additionally, her CSF lactate/pyruvate and serum beta-hydroxybutyrate/acetoacetate ratios were high, and levels of oxidative phosphorylation in skin fibroblasts were reduced. We therefore diagnosed Leigh syndrome. Genomic investigation confirmed the presence of compound heterozygous GFM2 mutations (c.206+4A>G and c.2029-1G>A) in both siblings, causing aberrant splicing with premature stop codons (p.Gly50Glufs*4 and p.Ala677Leufs*2, respectively). These findings suggest that GFM2 mutations could be causative of a phenotype of Leigh syndrome with arthrogryposis multiplex congenita.

Infant Motor Development Recovery after Surgery of Post TraumaticEpilepsy (PTE) - Meaningful Change of Fractional Anisotropy (FA) of MRIDiffusion Tensor Imaging (DTI) in a Case of Growing Skull Fracture

Epileptic seizure in pediatric patients affects neurodevelopment, and surgical treatment of intractable epilepsy improved comorbidities, but the mechanism is not fully uncovered yet. By measurement of MRI-DTI Fractional Anisotropy (FA) of posterior limb of internal capsule (PIC) of infants, we presented its change by seizure propagation and control in a case of an infant post traumatic epilepsy (PTE) caused by growing skull fracture. Her motor developmental delay and hemiparesis with non-convulsive status epilepticus (NCSE) started 2 months after injury, recovered after surgical repair and seizure control. FA of PIC was lower than normal (0.29 ipsilateral, 0.37 contralateral) had increased to normal range in one week after surgical treatment and seizure control (0.62, 0.66). Comparing with normal time course of FA of motor tract of infant, this dynamic change of FA indicated the effect of seizure control after surgical treatment. As measurement of other brain lesion also showed increased FA in both ipsilateral and contralateral deep white matter, indicated the effect of NCSE for wide network of brain, and influenced infant neuronal development. These result indicated one mechanism why NCSE affected motor developmental delay and surgical intervention for regional infant intractable epilepsy prevented further developmental delay. By handy method of measuring FA of motor tract, we had one possibility to predict motor tract injury in infancy. We also reviewed and discussed about the mechanism of FA increase and decrease in early infancy and how PTE caused FA change.

Subcortical heterotopia appearing as huge midline mass in the newborn brain.

IntroductionWe report the case of a 2-year-old boy who showed a huge midline mass in the brain at prenatal assessment.Case reportAfter birth, magnetic resonance imaging (MRI) revealed a conglomerate mass with an infolded microgyrus at the midline, which was suspected as a midline brain-in-brain malformation. MRI also showed incomplete cleavage of his frontal cortex and thalamus, consistent with lobar holoprosencephaly. The patient underwent an incisional biopsy of the mass on the second day of life. The mass consisted of normal central nervous tissue with gray and white matter, representing a heterotopic brain. The malformation was considered to be a subcortical heterotopia. With maturity, focal signal changes and decreased cerebral perfusion became clear on brain imaging, suggesting secondary glial degeneration. Coincident with these MRI abnormalities, the child developed psychomotor retardation and severe epilepsy focused on the side of the intracranial mass.

Paroxysmal Tonic Upward Gaze Complicating Angelman Syndrome

BACKGROUND Paroxysmal tonic upward gaze is a childhood oculomotor syndrome characterized by episodes of conjugate upward deviation of the eyes. Its pathogenesis is unknown, and the etiology is heterogeneous. PATIENT DESCRIPTION We describe a 2-year-old girl with Angelman syndrome who developed paroxysmal tonic upward gaze at 9 months of age. She presented with developmental delay, blond hair, jerky movements, ataxia, and epilepsy. Genetic testing revealed a maternal deletion of 15q11-13, confirming Angelman syndrome. CONCLUSIONS This is the first report of Angelman syndrome complicated by paroxysmal tonic upward gaze. Both transient paroxysmal tonic upward gaze and Angelman syndrome have been associated with dopaminergic neurons. We speculate that the dopaminergic abnormalities present in Angelman syndrome may cause paroxysmal tonic upward gaze.

Two Cases of Infantile Spasms Complicated by Urolithiasis Developed fora Short Period of Time during ACTH-Zonisamide Therapy

A 19-month-old female and a 16-month-old male child with intractable seizures were diagnosed as infantile spasms on the basis of their symptoms, clinical courses and EEGs. Both of them were born at 23 weeks gestation. We treated them by combination therapy with adrenocorticotrophic hormone (ACTH) and zonisamide (ZNS). However, urolithiasis was confirmed by computed tomography at 10 days and 12 days, respectively, after starting the combination therapy. We need to recognize that combination therapy with ACTH and ZNS carries a high risk of development of urolithiasis, and this adverse effect can happen at an early date. Regular urinalysis should be performed during therapy with these drugs, and if the presence of urolithiasis is suspected, CT scan or renal ultrasonography should be performed.