Chisako Fukuda

Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study

Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme‐replacement and substrate‐reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD.

Congenital mirror movement: a study of functional MRI and transcranial magnetic stimulation

Two male patients (a child and an adult) with congenital mirror movement were studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Bilateral primary sensorimotor cortices were activated during unilateral hand gripping on fMRI when the child patient was 8 years old andthe adult was 37 years old. Bilateral motor evoked potentials were induced from the hand and forearm muscles after TMS of each hemisphere. Bilateral motor responses were also induced from the arm muscles in the adult patient. Bilateral motor responses had short and similar latencies. Contralateral motor responses to TMS were smaller than ipsilateral ones in the hand muscles, while contralateral responses were larger than ipsilateral ones in the arm muscles. Contralateral hand motor responses reduced in amplitude or disappeared with increasing age while in the child patient, mirror movements decreased gradually. Our results suggest that bilateral activation of the primary sensorimotor cortices during intended unilateral hand movement and bilateral motor responses to TMS account, at least in part, for the pathophysiology of congenital mirror movement. Reduction of contralateral hand motor responses may be related to the decrease in mirror movements during development.

Low signal intensity and increased anisotropy on magnetic resonance imaging in the white matter lesion after head trauma: Unrecognized findings of diffuse axonal injury

We report on a four-year-old girl with head trauma caused by a motor vehicle accident. She presented with delirium, oculomotor palsy and ptosis in her left eye, left hemiparesis, and pyramidal signs in all extremities. Computed tomography on the day of admission showed diffuse cerebral edema with right-sided predominance. Magnetic resonance images on day 3 of admission showed lesions of diffuse axonal injury and contusion in the corpus callosum and right occipital and bilateral temporal lobes. There was a low-intensity lesion in the white matter of the right hemisphere on T2-weighted images, fluid-attenuated inversion recovery, T2()-weighted images, apparent diffusion coefficient maps and diffusion-weighted images. This low-intensity lesion disappeared by day 7, and a transient brain atrophy in the right hemisphere appeared on day 28. The low signal intensity in the cerebral white matter was apparently different from that associated with contusion and typical diffuse axonal injury, and might represent a late-onset accumulation of non-heme iron and free radicals in the white matter after head trauma.

Re-evaluation of short latency somatosensory evoked potentials (P13, P14 and N18) for brainstem function in children who once suffered from deep coma.

One of the major clinical features of brain death is deep coma. Therefore, we re-evaluated retrospectively electrophysiological examinations of brainstem function in about 31 children who had once suffered from deep coma in order to reveal its pathophysiological characteristics. The patient age at coma ranged from 1 month to 10 years (mean 2 years 1 month). The electrophysiological examinations were performed, including any of short-latency somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP) and blink reflexes. We first compared results between the fair and poor prognostic groups, and then re-evaluated SSEP results on a few severely impaired patients with persistent vegetative state (PVS). Subsequently, SSEP clarified more specific findings for a deep coma condition than BAEP and blink reflex. A lack of P14, N18 and N20, and an amplitude reduction or vagueness of P13 in SSEP in these children strongly suggested high risk in their future neurological prognosis. In conclusion, electrophysiological examinations, especially SSEP (P13, P14 and N18), might be very useful in obtaining a long-term neurological prognosis after deep coma in children.

Lower brainstem dysfunction in an infant with persistent primitive trigeminal artery

A 6-month-old boy with persistent primitive trigeminal artery (PPTA) presented with stridor, dysphagia, delayed motor development and postural neck and shoulder dystonia. Magnetic resonance imaging/angiography and ultrasonography revealed PPTA, with flow from the dilated basilar artery to the right internal carotid artery, lower brainstem compression by the dilated basilar artery, and cerebellar vermis hypoplasia. Evoked potentials showed lower pons and medulla oblongata functional disruption. These lesions may be related to vascular etiology in the lower brainstem or to congenital malformation syndrome involving infratentorial structures. The relationship of this condition to Möbius syndrome is discussed.

Topographic MN-SSEPs (N18, N20 and N30) might characterize underlying CNS involvements in representative types of cerebral palsy

This study is aimed at constructing the neurophysiological basis for determining the characteristic features of cerebral motor disturbance in representative cerebral palsy (CP) types using topographical S-SEPs technology. Median-nerve stimulated S-SEPs (MN-SSEPs) were examined for 23 patients with four representative types of cerebral palsy: 6 athetotic (including 3 patients due to hypoxic-ischemic encephalopathy (HIE) and 3 to kernicterus), 7 hemiplegic, 5 diplegic and 5 tetraplegic types, and 13 normal controls. In HIE group of athetotic CP, frontal N30 specifically showed severe amplitude reduction or abolishment. In hemiplegic CP, both N20 and N30 on the affected cerebral side tended either to disappear or to be normally evoked at the same time, and their mean amplitudes declined severely. In diplegic CP, the amplitudes of subcortical N18 and parietal N20 were not small but significantly enlarged. N30 amplitude stayed within normal. The reason for this unexpected enlargement of N18 and N20 is unclear, but may be partly due to premature birth which caused abnormally abundant dendritic spine due to absence from perinatal normal spine elimination in the brainstem. In several quadriplegic patients, both N20 and N30 disappeared. The mean amplitude of N30 severely decreased. In conclusion, topographical results of N18, N20 and N30 may basically suggest the underlying involvement of nervous structures in CP according to their representative type.

Disappearance of frontal N30 component of median nerve stimulated SSEPs in two young children with abnormal striatal lesions

Median nerve stimulated short-latency somatosensory evoked potentials (MN-SSEPs) were performed in two young children with extrapyramidal symptoms. Brain MRI showed bilaterally symmetric striatal lesions in both cases. The subcortical components (N9, N11, N13, N18, P11, and P13) and the parietal component (N20) were normally detected, whereas the frontal component (N30) was not detected bilaterally in either case. In conclusion, our findings suggest that frontal N30 disappearance could be observed since as early as young childhood and it may pathophysiologically reflect severe dysfunction in the extrapyramidal system.

Surface electromyogram and muscle ultrasonography for detection of muscle fasciculations in pediatric peripheral neuropathy

A 12-year-old girl presented with talipes equinus of both legs, attenuation of upper and lower limb tendon reflexes, thermal hyperalgesia, and reduction of vibratory sensation. On clinical examination, muscle twitches of fingers of both hands, as well as the abductor halluces and the dorsal interossei muscles of the right foot were observed. Nerve conduction velocity was significantly declined in the upper and lower extremities. Needle electromyography (EMG) was not performed; however, ultrasonography revealed repetitive, semi-regular muscle twitches lasting 0.2-0.4s, concomitant with muscle discharges on surface EMG in the right foot muscles. These findings were compatible with contraction fasciculation in muscles under chronic reinnervation. Nerve and muscle biopsies were suggestive of chronic motor, sensory, and autonomic neuropathy. This is the first case of pediatric peripheral neuropathy where muscle fasciculation was noninvasively identified by simultaneous surface EMG and ultrasonography.