Masahito Miyazaki

Development of the Brainstem and Cerebellum in Autistic Patients.

Studies of magnetic resonance images have revealed morphological disorders of the brainstem and cerebellum in autistic children and adults. When we studied development of the brainstem and cerebellum in autistic patients, we found that although the brainstem and cerebellum significantly increased in size with age in both autistic patients and controls, these structures were significantly smaller in autistic patients than in controls. The speed of development of the pons, the cerebellar vermis I–V and the cerebellar vermis VI–VII was significantly more rapid in autistic patients than in the controls. However, the speed of development of the other brain structures in the posterior fossa did not differ between autistic patients and controls. The regression intercepts of the brainstem and cerebellum as well as those of their components were significantly smaller in autistic patients than in controls. Results suggest that brainstem and vermian abnormalities in autism were due to an early insult and hypoplasia rather than to a progressive degenerative process.

DEVELOPMENTAL BRAIN CHANGES INVESTIGATED WITH PROTON MAGNETIC RESONANCE SPECTROSCOPY

Volume‐selective proton magnetic resonance spectroscopy (1H‐MRS) of the brain was performed with a 1.5 Tesla magnet in 47 healthy children and in six healthy adults. Peaks of N‐acetylaspartate (NAA), choline (Clio) and creatine (Cr) were observed in all cases, but a lactate peak was not observed. In the right parietal region, I H‐MRS revealed increases in the rations of NAAJCho and NAA/Cr and a decrease in Cho/Cr with advancing age. The most rapid changes were noted between one and three years of age. 1H‐MRS of the right frontal region also was performed in 21 cases (20 children and one adult). In the right frontal region, there was an increase in the ratio of NAA/Cho and a decrease in Cho/Cr with advancing age, while a developmental change was not observed in the ratio of NAA/Cr. The ratios of both NAA/Cho and NAA/Cr were lower in the right frontal region than in the right parietal region. These results show that developmental changes and regional variation of metabolites are observed in 1 H‐MRS of the brain, and need to be considered in its application.

Brainstem and cerebellar vermis involvement in autistic children.

Recent reports have suggested functional abnormalities of the brain stem in autistic children, and structural abnormalities have also been reported. We obtained magnetic resonance imaging (MRI) scans for 21 autistic children and compared them with 21 control MRI scans. The areas of the brain stem and cerebellar vermis were measured using midsagittal images. The brain stem and cerebellar vermis lobules VIII to X were found to be significantly smaller in autistic children. A positive correlation between the size of the brain stem and cerebellar vermis was observed in the autistic children. This correlation was not observed in the control children. This suggests that the size of the brain stem and cerebellar vermis are anatomically altered in autistic children and that growth of the brain stem and cerebellar vermis in autistic children is different from normal children. (J Child Neurol 1992;7:149-153).

Evaluation of the GABAergic nervous system in autistic brain : 123I-iomazenil SPECT study

PURPOSE To evaluate the GABA(A) receptor in the autistic brain, we performed (123)I-IMZ SPECT in patients with ASD. We compared (123)I-IMZ SPECT abnormalities in patients who showed intellectual disturbance or focal epileptic discharge on EEG to those in patients without such findings. SUBJECTS AND METHODS The subjects consisted of 24 patients with ASD (mean age, 7.3±3.5 years), including 9 with autistic disorder (mean age, 7.0±3.7 years) and 15 with Aspergers disorder (mean age, 7.5±3.2 years). We used 10 non-symptomatic partial epilepsy patients (mean age, 7.8±3.6 years) without intellectual delay as a control group. For an objective evaluation of the (123)I-IMZ SPECT results, we performed an SEE (Stereotactic Extraction Estimation) analysis to describe the decrease in accumulation in each brain lobule numerically. RESULTS In the comparison of the ASD group and the control group, there was a dramatic decrease in the accumulation of (123)I-IMZ in the superior and medial frontal cortex. In the group with intellectual impairment and focal epileptic discharge on EEG, the decrease in accumulation in the superior and medial frontal cortex was greater than that in the group without these findings. CONCLUSION The present results suggest that disturbance of the GABAergic nervous system may contribute to the pathophysiology and aggravation of ASD, since the accumulation of (123)I-IMZ was decreased in the superior and medial frontal cortex, which is considered to be associated with inference of the thoughts, feelings, and intentions of others (Theory of Mind).

Reduced brainstem size in children with autism

Recently, structural brain abnormalities as well as functional abnormalities of the brainstem have been reported in autistic children. The authors undertook an analytic study of the brainstem in autistic children by means of magnetic resonance imaging (MRI). The MRI scans of 29 autistic children were compared with 15 control MRI scans. The autistic children were divided into two groups according to DQ (IQ) level: the DQ (IQ) greater than or equal to 80 group and the DQ (IQ) less than 80 group. The midbrain and pons were measured, and the ratio of the midbrain and pons sizes versus the cranium size were calculated. The brainstem size was found to be significantly smaller in the autistic group. In particular, the reduction in brainstem size tended to be greater in the low DQ (IQ) group when compared with the high DQ (IQ) one, though there was no significant difference (p less than 0.1). This suggests that the brainstem is anatomically altered in autistic children.

Brainstem involvement in high functioning autistic children

To determine involvements of the brainstem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. A positive correlation between age and area of the cerebellar vermis was observed in autistic children but not in control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children and that growth of the cerebellar vermis in autistic children was different from normal children.

Differences in brain metabolites between patients with autism and mental retardation as detected by in vivo localized proton magnetic resonance spectroscopy.

We performed volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain with a 1.5 T magnet in 28 patients with autism, and compared the results with those from 28 age-matched patients with unclassified mental retardation and 25 age-matched healthy children. Peaks for N-acetylaspartate, choline and creatine, but not lactate, were observed in each group on 1H-MRS. The N-acetylaspartate/choline ratio was lower in patients with mental retardation than in patients with autism and controls (P = .05, respectively). However, there were no differences in the N-acetylaspartate/ choline ratios between patients with autism and controls, and the N-acetylaspartate/creatine and choline/creatine ratios did not differ among the three groups. These results suggest that N-acetylaspartate is decreased in patients with mental retardation and that a disorder or dysfunction of neurons in the brain exists. There also appear to be differences in the brain lesions or dysfunctions found in patients with autism and mental retardation. (J Child Neurol 1997;12:91-96).

Neuroimaging study of myotonic dystrophy. I. Magnetic resonance imaging of the brain

Magnetic resonance imaging scans of the brain were obtained in 13 patients with myotonic dystrophy, seven with congenital myotonic dystrophy and six with adult-type myotonic dystrophy. All seven patients with congenital myotonic dystrophy had ventriculomegaly and a low IQ (DQ). Cerebral white matter lesions were observed in six cases, a small corpus callosum in four cases, a small brainstem in two cases, and a cerebellar white matter lesion in one case. Cerebral white matter lesions were observed in five of the six cases with adult-type myotonic dystrophy of which one had ventriculomegaly. The IQ (DQ) was significantly lower in patients with congenital myotonic dystrophy than in those with adult-type myotonic dystrophy. The incidence of a small corpus callosum or ventricular enlargement was higher in congenital myotonic dystrophy than in adult-type myotonic dystrophy. These findings may be related to the presence of neurologic impairment in congenital myotonic dystrophy.

Magnetic resonance imaging of the brain structures in the posterior fossa in retarded autistic children

Midsagittal magnetic resonance images of the brains of retarded autistic children were compared to those of non‐autistic mental retardation patients and controls. We found that the whole brain stem and particularly two of its components (the midbrain and medulla oblongata) were significantly smaller in retarded autistic children and mental retardation cases than in control children. The pons area was significantly smaller in mental retardation cases as compared to control children but did not differ between autistic and control children. Moreover, there was no difference in the brain stem between retarded autistic children and mental retardation cases. We also noted no difference in the cerebellar vermis area among retarded autistic children, mental retardation cases and control children. The ratio of the midbrain to posterior fossa area was significantly smaller only in autistic patients. Although the significance of these results is unknown, further examination of autistic children with a normal IQ is necessary.

CSF β-Endorphin Levels in Patients with Infantile Autism

We measured CSF levels of β-endorphin, an opioid hormone, in 19 patients with infantile autism and in 3 patients with Rett syndrome, and compared them with control values. In infantile autism, CSF levels of β-endorphin did not differ significantly from those of age-matched controls. There was no significant correlation between CSF levels and clinical symptoms, including self-injurious behavior, pain insensitivity, and stereotyped movement. However, CSF levels of β-endorphin were significantly higher in the patients with Rett syndrome than in the control (p < .05). Data suggest that neurons containing β-endorphin may not be involved in patients with infantile autism. Thus, there is no relationship between dysfunction of brain opioid and autism.