Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic ; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse (“volume transmission”). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD.
The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD.
Finally, I would like to emphasize that it is crucial in the field of child neurology medical examination and treatment should be based on the basic neuroscience, always taking “neurons” into consideration.

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A total of 43 patients with severe motor and intellectual disabilities were enrolled in videofiberscopic investigation of laryngeal abnormalities. Their ages ranged from 2 to 41 years (mean: 19.9 years) and all of them had severe quadriplegia due to cerebral palsy or other conditions. Thirty-two out of the 43 patients (74.4%) had laryngeal abnormalities; laryngeal stenosis including that of iatrogenic origin, hypersecretion and laryngomalacia. Direct visualization of the occurrence of aspiration could be achieved in some patients. Seven (87.5%) out of 8 patients with tracheostomy and 25 (71.4%) out of 35 patients without tracheostomy had laryngeal abnormalities, showing no significant difference. The prevalence of abnormalities was significantly higher in patients with parenteral nutrition (30/33=90.9%) than in those with oral feeding (2/10=20%). Endoscopic investigation of the larynx is important, and videofiberscopy is especially effective for evaluation of laryngeal abnormalities in severely handicapped patients.

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We investigated the usefulness of electrodiagnostic (EDX) studies for the early diagnosis of childhood Guillain-Barré syndrome (GBS). We retrospectively reviewed 5 patients (ages, 17-96 months) who fulfilled the diagnostic criteria of GBS. The EDX studies were performed at least twice; they included 1 or more following: motor nerve conduction study (MNCS), F-wave study, electromyography (EMG), and sensory nerve conduction study. The first and second EDX studies were performed at 8 days (range: 4-13 days) and 14 days (range: 12-27 days) after the onset of motor symptoms, respectively.
Although only 3 of 5 patients showed abnormal findings in the first MNCS, additional EDX studies, namely, F-wave study and EMG confirmed the presence of peripheral neuropathy in all patients. Regarding the classification of GBS subtypes, the results of the first EDX studies lead to the diagnosis of acute inflammatory demyelinating polyneuropathy (AIDP) in 3 patients and the remaining two were diagnosed with AIDP based on results of the second studies.
We concluded that serial EDX studies, including F-wave studies, are essential for the early and definite diagnosis of childhood GBS.

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We recently evaluated a patient with ADEM after a mycoplasma infection who initially presented with psychiatric symptoms, including hyperkinesis, irritability, and emotional outbursts. Psychiatric symptoms in ADEM are rare and usually suggest some underlying psychiatric or psychogenic disorder. This case illustrates that in children who initially present with psychiatric symptoms, even in the absence of typical neurologic symptoms associated with encephalitis such as disturbance of consciousness or seizures, ADEM should be considered in the differential diagnosis. Recent history of infections or vaccinations should also be considered.

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An 11-month-old boy with multiple congenital anomalies developed West syndrome and ACTH therapy was started. Marked bradycardia during sleep was observed after the 16th day of ACTH therapy. Echocardiography revealed both intraventricular septum and left ventricular free wall thickening with preservation of biventricular function. Both the patient's marked sinus dysfunction and his cardiac hypertrophy were suspected to be related to the ACTH therapy. Sinus function gradually improved after ACTH therapy was withdrawn and treatment with oral β-agonist was started.
We believe that the patient's sinus dysfunction and cardiac hypertrophy were caused by ACTH treatment because of the subacute nature of the onset and the absence of other potentially contributory factors such as infection or respiratory failure. Pediatricians should be aware that cardiac dysfunction could be associated with ACTH therapy for West syndrome.

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Restless legs syndrome (RLS) has gradually been recognized as a cause for insomnia in adults, but there have been few reports about children with RLS in Japan. Here we described seven pediatric RLS patients. All of the parents of our patients had difficult times to make their children sleep due to irritability, restlessness, and demanding bedtime routines. All patients had asked their parents to rub their feet in bed, and it took more than half an hour to soothe them until they fell asleep. Their mothers had been exhausted from this night-time routine. However, they did not consider the routine abnormal, as it had been their habitual behavior since infancy. Some parents were too distressed or embarrassed to describe the symptoms of their child properly. Five patients had clear family history and none had obvious periodic leg movements during sleep. All patients showed low levels of ferritin and iron supplementation was effective in five cases. In the severest two cases, pramipexole, but not iron, was dramatically effective. Both patients started to show RLS symptoms in the early days of infancy, which may suggest more severe hereditary dopaminergic dysfunction. RLS does occur in childhood and pediatricians should bear it in mind as one of the differential diagnoses when seeing children who are irritated and/or having difficulty in initiating their sleep.

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We diagnosed a Japanese female as having severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) syndrome. Genetic analysis revealed a K650M point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, described in only six other individuals in the world. The medical history of the present case includes severe skeletal dysplasia at birth, progressive acanthosis nigricans in infancy, and severe central nervous system structural abnormalities, consisting of the absence of right cerebral hemisphere (hydranencephaly), ventricular dilatation, both indicating congenital brain malformation, and porencephaly indicating destructive brain damages. The patient is severely retarded and has suffered from intractable seizures. This is the first report of a Japanese patient and the seventh case of SADDAN syndrome confirmed genetically.

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DYT1 dystonia (DYT1-D, early-onset torsion dystonia) is caused by a GAG deletion in the DYT1 gene. Here we report a girl with child-onset familial DYT1-D showing localized arm involvement. The patient developed postural and action dystonia in the right and left arms at 7 and 9 years, respectively. She was misdiagnosed as hysteria due to lack of abnormalities on laboratory tests. At 11 years of age she was introduced to our clinic. Increased muscle tonus and dystonic discharges seen on surface electromyogram in the right arm and the sternocleidomastoid muscle led to the diagnosis of dystonia. A GAG deletion in the DYT1 gene was confirmed in the patient, her healthy father and paternal grandfather with torsion dystonia. Titration of levodopa resulted in the fluctuation of her arm dystonia. Combined therapy by levodopa and trihexyphenidyl relieved postural dystonia in the right arm but not action dystonia in the left. Both types of dystonia in the right and left arms were well ameliorated by the additional increase of levodopa. Somatosensory evoked potentials demonstrated abnormal premovement gating. The latency and accuracy of the amplitude were disturbed in visually guided saccadic eye movement. Now at more than 11 years after onset, the patient has not shown torsion or involvement of the lower extremities. Most DYT1-D patients are refractory to medication and early surgical intervention is recommended. However, the presence of DYT1-D patients showing a milder disease course should also be considered.

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[in Japanese]

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[in Japanese]

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