Early cerebellar lesions impair eyeblink conditioning in developing rats: Differential effects of unilateral lesions on Postnatal Day 10 or 20.

Experiment 1 demonstrated that the ipsilateral cerebellar hemisphere is essential for the acquisition of eyeblink conditioning in infant rats and that cerebellar lesions given on Postnatal Day 10 (PND10) produced deficits in eyeblink conditioning when given to either hemisphere. For both hemispheres, lesions that were restricted to the cerebellar cortex produced less severe deficits than lesions that included the deep nuclei. Experiment 2 showed that the age at which the cerebellar lesions occurred determined whether damage to the contralateral cerebellar hemisphere impaired conditioning. Lesions of either the ipsilateral or contralateral hemisphere that included the deep nuclei disrupted eyeblink conditioning when given on PND10. In contrast, when lesions were given on PND20, ipsilateral lesions that included the deep nuclei abolished conditioning, while the same lesion given to the contralateral hemisphere had no effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical and molecular features of spinocerebellar ataxia type 6

The mutation involved in spinocerebellar ataxia type 6 (SCA6) is a small CAG expansion in the alpha-1A subunit of the voltage-dependent calcium channel gene. We looked for this mutation in 91 families with autosomal-dominant cerebellar ataxias and found that SCA6 is a minor locus in our series (2%) and is rare in France (1%). Furthermore, we did not detect the SCA6 mutation on 146 sporadic cases with isolated cerebellar ataxia or olivopontocerebellar atrophy. The normal and expanded alleles ranged from 4 to 15 and 22 to 28 CAG repeats, respectively, and age at onset was correlated to CAG repeat length (r = -0.87). In contrast with other SCA, the expanded allele was stable during transmission. Clinically, SCA6 patients (n = 12) presented with moderate to severe cerebellar ataxia with a lower frequency of associated signs compared with other SCA and a mean age at onset of 45 +/- 14 years (range, 24 to 67). MRI showed extensive cerebellar atrophy but not of the brainstem or cerebral cortex.     

A case of juvenile onset ataxia with dystonia, myoclonus, sensorineural hearing loss and mental retardation

A 35-year-old female was reported who presented early onset and slowly progressive ataxia and retrocollis which appeared at the age of nine. On admission, neurological examination revealed cerebellar ataxia, dystonia of the neck and the right arm, myoclonus of the neck and the shoulder, slight mental retardation, supranuclear upper gaze palsy, and sensorineural hearing loss. Laboratory examination showed high serum CK activity. Electromyography and muscle biopsy findings suggested slight muscular involvement. CSF level of HVA and 5-HIAA were reduced. MRI demonstrated marked cerebellar atrophy and slight atrophy of the brain stem. To our knowledge, the characteristic combination of the neurological sign in this case has not been reported. This case was compared with EOCA (early onset cerebellar ataxia with retained tendon reflexes) and other juvenile onset cerebellar ataxia and dystonia.     

Spinocerebellar ataxia type 6. Molecular and clinical features of 35 Japanese patients including one homozygous for the CAG repeat expansion

Spinocerebellar ataxia type 6 (SCA6) is a newly classified autosomal-dominant cerebellar ataxia (ADCA) associated with CAG repeat expansion. We screened 111 patients with cerebellar ataxia for the SCA6 mutation. Of these, 35 patients were found to have expanded CAG repeats in the SCA6 gene, indicating that second to SCA3, SCA6 is the most common ADCA in Japan. Expanded alleles ranged from 21 to 29 repeats, whereas normal alleles had seven to 17 repeats. There was no change in the CAG repeat length during meiosis. The age at onset was inversely correlated with the repeat length. The main clinical feature of the 35 patients with SCA6 was slowly progressive cerebellar ataxia; multisystem involvement was not common. The 35 patients included nine cases without apparent family history of cerebellar ataxia. The sporadic cases had smaller CAG repeats (21 or 22 repeats) and a later age at onset (64.9 +/- 4.9 years) than the other cases with established family history. We also identified one patient who was homozygous for the SCA6 repeat expansion. The homozygote showed an earlier age of onset and more severe clinical manifestations than her sister, a heterozygote carrying an expanded allele with the same repeat length as the homozygote. This finding suggests that the dosage of the CAG repeat expansion plays an important role in phenotypic expression in SCA6.     

The development of the cerebellar cortex of the Syrian hamster, Mesocricetus auratus. Foliation, cytoarchitectonic, Golgi, and electron microscopic studies

Although a number of investigations of abnormalities of cerebellar development have been carried out in the hamster, no detailed Golgi or ultrastructural studies of cerebellar development in this species have been reported. This report describes the development of the hamster cerebellar cortex from birth (day 0) through postnatal day 78, as studied by light, Golgi, and electron microscopic methods. Foliation patterns correlate with the expansion of the cerebellar layers and of total cerebellar area. Cytologic and morphologic development of the major cerebellar cell types--Purkinje, Golgi, basket, stellate, granule, and Bergmann glial cells--correlate with those of other species, such as the rat and mouse. Electron microscopic observations at selected developmental ages allow identification and classification of synapses in the early postnatal hamster. Parallel fiber and climbing fiber synapses are already present at birth. Although synaptogenesis probably continues through the first two postnatal months, all major cell types have developed initial synapses by postnatal day 6, at a time when little cellular maturation has occurred. By using gestational rather than natal age, close developmental correlations between hamsters and rat and mouse are possible. Since the gestational period of the hamster is only 16 days, the hamster cerebellum is less mature at birth than that of either the rat or mouse. Thus, the hamster is a convenient animal in which to investigate the effects of various procedures on early cerebellar development.     

Early transvaginal measurement of transcerebellar diameter in Down syndrome

OBJECTIVE: To evaluate the screening utility of early transvaginal measurement of the transverse cerebellar diameter for identification of Down syndrome fetuses. METHOD: Measurements of the transverse cerebellar diameter were obtained by transvaginal sonography between 11 and 16 weeks of gestation in 544 fetuses with a normal karyotype and in 37 Down syndrome fetuses. RESULTS: The transverse cerebellar diameter was found to show a fairly constant increment of values throughout the period evaluated with a linear relationship to the gestational age. The measurements obtained in Down syndrome fetuses are within the normal range for gestational age. CONCLUSION: The transverse cerebellar diameter cannot be considered a useful tool in the detection of Down syndrome in early pregnancy.     

Associative learning in patients with cerebellar ataxia

It has been claimed that patients with cerebellar pathology are impaired at associative learning. Patients with cerebellar ataxia (n = 7) were taught a visual-motor associative task. The task was chosen so as to allow comparisons with data currently being collected on the effects of cerebellar lesions on associative learning in monkeys. As a group the patients were as impaired at learning the task as a group of 8 patients with Huntington's disease. When each patient was individually matched with a control of the same age and IQ, some patients with cerebellar ataxia were found to be clearly impaired, but 2 were not. Of the 4 patients who were most clearly impaired, 2 had brainstem pathology and 2 did not. The relevance of these findings is discussed in relation to views concerning the functions of the cerebellum.     

Impairment in shifting attention in autistic and cerebellar patients.

Magnetic resonance imaging (MRI) and autopsy evidence of early maldevelopment of cerebellar vermis and hemispheres in autism raises the question of how cerebellar maldevelopment contributes to the cognitive and social deficits characteristic of autism. Compared with 18 normal controls, 8 autistic patients (mean age 13.9 yrs) and 6 patients (mean age 8.6 yrs) with acquired cerebellar lesions were similarly impaired in a task requiring rapid and accurate shifts of attention between auditory and visual stimuli. Neurophysiologic and behavioral evidence rules out motor dysfunction as the cause of this deficit. These findings are consistent with the proposal that in autism cerebellar maldevelopment may contribute to an inability to execute rapid attention shifts, which in turn undermines social and cognitive development. Findings support the proposal that the human cerebellum is involved in the coordination of rapid attention shifts in a fashion analogous to its role in the coordination of movement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo

The major aim was to identify predictors of the large age differences that exist in eyeblink classical conditioning. Eyeblink conditioning was assessed in 190 participants over the age range of 20-89 years, with 150 trained in the paired condition and 40 trained in the explicitly unpaired control condition. Timed-interval tapping was used to assess cerebellar function. Blink reaction time and explicit learning and memory were also assessed. Stepwise multiple regression indicated that the effect of age accounted for the largest proportion of the variance, but the cerebellar measure also predicted eyeblink conditioning at a significant level. Reaction time and explicit memory measures did not account for a significant amount of the variance in eyeblink conditioning. Age-related effects in the cerebellum apparently affect timing and learning in normal adults.     

Studies on multiple factor intervention in stroke of ten areas in northeast, north China and Shanghai]

Growth of the fetal cerebellum was monitored by transverse cerebellar diameter (CD) from 14 to 39 weeks menstrual age in 125 Japanese fetuses. The growth curve for this parameter was determine using a Rossavik growth model [p = c(t)k & (t)]. An R2 value of 95.5% was obtained for CD. Variability analysis indicated a progressive increase in variability with fetal age for this parameter. Variability data were used with the growth curve model to determine a standard curve for this parameter. This standard curve provides a superior means to evaluate normal fetal cerebellar growth in the fetus and to identify cerebellar abnormalities in utero.     

Predictors of eyeblink classical conditioning over the adult age span.

The major aim was to identify predictors of the large age differences that exist in eyeblink classical conditioning. Eyeblink conditioning was assessed in 190 participants over the age range of 20–89 years, with 150 trained in the paired condition and 40 trained in the explicitly unpaired control condition. Timed-interval tapping was used to assess cerebellar function. Blink reaction time and explicit learning and memory were also assessed. Stepwise multiple regression indicated that the effect of age accounted for the largest proportion of the variance, but the cerebellar measure also predicted eyeblink conditioning at a significant level. Reaction time and explicit memory measures did not account for a significant amount of the variance in eyeblink conditioning. Age-related effects in the cerebellum apparently affect timing and learning in normal adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Secondary changes in cerebellar perfusion (diaschisis) in hemiplegia during childhood: SPECT study of 55 children

Diaschisis is a functional impairment at a site in the brain remote from the lesion causing it. An investigation of cerebellar diaschisis in childhood was undertaken to better understand the functional maturation of the corticopontocerebellar tract in developing brain. A retrospective study of cerebellar diaschisis in 55 hemiplegic children was conducted using single-photon emission computed tomography (SPECT) with 123I-IMP. Cerebellar diaschisis was evaluated by 2 authors. Crossed cerebellar diaschisis (CCD) was found in 6 of 55 patients. SPECT findings of patients who presented with CCD disclosed supratentorial hypoperfusion of varying degrees, from focally to the whole hemisphere; however, patients had frontal and/or parietal hypoperfusion in common. A second type of cerebellar diaschisis also was demonstrated. Cerebellar hypoperfusion ipsilateral to supratentorial lesions, ipsilateral cerebellar diaschisis (ICD), was observed in 10 of 55 patients. CCD occurred in the patients who suffered from brain injuries after 7 years, 5 months of age, while ICD manifested in patients whose brain injuries occurred before 3 years, 1 month of age. The production of remote effects, such as CCD and ICD, could be closely related to maturation of the corticopontocerebellar tract in the developing brain during childhood.     

Cerebellar growth in normal and growth-restricted fetuses of multiple gestations

OBJECTIVE: Our purpose was to evaluate growth of the cerebellum in growth-restricted fetuses of twin and triplet gestations versus growth in normal in utero sibling(s) and in singleton gestations. STUDY DESIGN: An ultrasonographic study was conducted in a population of pregnant women with twin and triplet gestations. The control group was either the normal in utero sibling(s) when one fetus was growth restricted or normal twin and singleton pregnancies. Standard biometric measurements were obtained on all fetuses throughout pregnancy, including the transverse cerebellar diameter. However, only the last measurement was used for the analysis. Statistical analyses were conducted comparing growth of the transverse cerebellar diameter among the growth-restricted fetuses versus growth in the normal in utero fetal sibling(s) or other normal twin and singleton gestations. RESULTS: Pregnancies were categorized on the basis of the growth status of women with twin and triplet gestations: Group 1 (151) contained women with two fetuses appropriately grown for gestational age; group 2 (52) had one appropriately grown fetus and one with intrauterine growth restriction; group 3 (19) had two fetuses with intrauterine growth restriction. In addition, there were 30 triplet gestations (group 4), five of which had growth-restricted fetuses, and group 5 contained 1405 singleton pregnancies. In all five groups there was a statistically significant relationship between transverse cerebellar diameter and gestational age (p < 0.0001). There was also no significant difference between growth of the transverse cerebellar diameter in the appropriately grown and growth-restricted siblings and among normal singleton and twin pregnancy groups. In most cases of growth-restricted fetuses, except for the transverse cerebellar diameter measurements, all other biometric parameters were < 10th percentile. CONCLUSION: These data confirm the relative preservation of normal cerebellar growth in growth-restricted fetuses and a similar rate of growth in singleton and multifetal gestations. The transverse cerebellar diameter therefore represents an independent biometric parameter that can be used in both singleton and multifetal pregnancies to assess normal and deviant fetal growth.     

Medulloblastoma and pineoblastoma in monozygous twins (author's transl)

Clinical and neuropathological findings in monozygous twin sisters are reported. Twin I died at age 5 months from a cerebellar medulloblastoma, whereas her sister died at age 16 months from a pineoblastoma. The tumors are considered similar referring to histogenesis, structural peculiarities and growth. Therefore, the twins are seen as concordant for the tumor type.     

Recurrent acute cerebellar ataxia of childhood following nonspecific respiratory tract infection

Acute cerebellar ataxia in childhood following viral infection is a self-limited disease. The disease with recurrent course has rarely been reported. At the Department of Pediatrics, Ramathibodi Hospital, three children with recurrent episodes of acute cerebellar ataxia following nonspecific viral infection were encountered. The age at onset of each patient was 2 years, 18 months and 2 years old. The clinical symptoms were similar and improved rapidly after gluco-corticoid was given. All patients recovered without residual deficit. Six, 5 and 3 recurrent attacks of similar illness were noted in each patient respectively after the first episode. However, no further attack occurred after the age of 5 years and the age of last follow-up was 17, 16 and 14 years old respectively. The pathogenesis of the recurrent episodes is uncertain. The abnormal immunological response is postulated.     

Development of cerebellar hypoplasia in jaundiced Gunn rats: a quantitative light microscopic analysis

The homozygous (ii) Gunn rat provides a model for hyperbilirubinemia which includes prominent cerebellar hypoplasia. Development of the Gunn rat cerebellum was examined with and without the additional effects of elevating brain bilirubin concentration to still higher levels via sulfadimethoxine (sulfa) administration. Homozygous (jj) Gunn rats and heterozygous (Nj) littermate controls (n = 32 each) were given 100 mg/kg sulfa or saline at postnatal days 3, 7, 17, and 30, and most were sacrificed 24 h later (n = 4 for each genotype at each age). Cerebellar volume, total volume and cell number for each deep cerebellar nucleus, densities for Purkinje and granule cells in the cerebellar cortex of lobules II, VI and IX, and the density of vacuolated Purkinje cells were all measured quantitatively. Cytoplasmic vacuolation provided an indication of bilirubin toxicity and was never observed in the Nj control rats. Vacuolated Purkinje cells were first observed in jj-saline rats at 18 days and were found only in the more anterior lobules of the cerebellum (II and VI). By contrast, vacuolated Purkinje cells were observed in jj-sulfa rats at both 4 and 8 days, but only in the most posterior cerebellar lobule (IX). In all older jj rats, the decline in vacuolation was accompanied by significant necrosis and resorption of the Purkinje cells in the anterior lobules. Since the Purkinje cells in the posterior lobules are the first to differentiate in the cerebellum and are resistant to bilirubin toxicity in jj-saline rats, the results support the presence of a critical period when elevated brain bilirubin may be most toxic to neuronal development. The findings suggest that neurons undergoing differentiation at the time of bilirubin exposure are most susceptible to cell death, while cells that are slightly more or slightly less mature may show only transient changes.     

A neuronal vacuolar disorder in young rottweiler dogs

Four rottweiler pups from two litters developed severe progressive signs of spinal ataxia, cerebellar ataxia and tetraparesis/paralysis. The signs started with ataxia of the pelvic limbs at seven to eight weeks of age and progressed to tetraparesis and paralysis within three to five weeks. Postmortem, a vacuolar neuronal disorder was found in the cerebellum, brainstem and the spinal cord, associated with Wallerian type degeneration in the brainstem, cerebellar peduncles and the medullary cord. Electron microscopy revealed empty membrane-bound vacuoles. Immunohistochemistry for PrPSc was negative. The disorder differs clinically and pathologically from other neurological disorders in the breed and a new (familial) neurological disorder in the rottweiler is suspected.     

Machado-Joseph disease: clinical, molecular, and metabolic characterization in Chinese kindreds

Machado-Joseph disease, an autosomal dominant multisystem motor degeneration, has been described mainly in people of Portuguese descent. Our report documents the presence of Machado-Joseph disease in the Chinese population, based on the specific molecular marker of a CAG repeat array in the 3' end of the MJD gene. We screened 21 Chinese families with dominant spinocerebellar ataxia. The results showed that Machado-Joseph disease with CAG expansion accounted for 52% of families with autosomal dominant cerebellar ataxia in this series. The clinical characteristics, besides the well-documented cerebellar ataxia, dysarthria, nystagmus, corticospinal dysfunctions, a variable degree of facial muscle fasciculation, and proprioceptive loss, included loss of optokinetic nystagmus and autonomic nervous system dysfunction. The CAG repeat number in the MJD gene ranged from 14 to 39 among normal alleles, and from 63 to 81 among MJD alleles. There was a strong inverse correlation (gamma = -0.77) between number of CAG repeats and age at symptom onset, accounting for 60% of the variance of age at onset. A strong clinical anticipation of age at onset existed in successive generations. Mild instabilities of expanded CAG repeat numbers during meiotic transmission occurred, with no significant difference according to the gender of the transmitting parent. Finally, brain metabolism in Machado-Joseph disease, studied with positron emission tomography, was characterized by significant progressive regional hypometabolism in the occipital cortex, as well as the cerebellar hemispheres, vermis, and brainstem.     

Task Switching After Cerebellar Damage.

The authors of this study investigated task switching following cerebellar damage. The study group consisted of 7 children and adolescents (M age = 13.8 years) who underwent surgical removal of a benign posterior fossa tumor. They were tested at a sufficient interval after surgery (M lag = 6.13 years) for restoration of normal cognitive skills and intelligence. Although all showed normal learning of the task compared with control participants, when rapid behavioral changes were required (short preparation time), they exhibited behavioral rigidity manifested by enhanced switching cost. These results are in line with another study on serial reaction time with the same patients (A. Berger et al., in press). They have important implications for our understanding of the cognitive sequelae of early cerebellar damage as well as the involvement of the cerebellum in task switching. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A transient CD15 immunoreactive sling in the developing mouse cerebellum

The distribution of the 3-fucosyl-N-acetyl-lactosamine (FAL, CD15) epitope in the developing mouse cerebellum was examined with the aid of immunohistochemistry of paraffin sections. CD15 immunoreactivity first appeared at E15 as a discrete bundle of processes lying beneath, and slightly within, the deeper layers of the external granular layer. By E17, when the cerebellar anlagen had completed their midline fusion, these processes could be traced from the germinal trigone at the lateral limits of the cerebellar anlage around the posterior cerebellar midline to the opposite germinal trigone. By P2, this sling was no longer apparent and CD15 immunoreactivity was confined to astrocytes in the cerebellar white matter, surrounding the deep cerebellar nuclei. The CD15 immunoreactive processes pursue an unusual trajectory through the developing cerebellum, unlike any other previously described axonal or glial process bundle in the cerebellum. From its trajectory and association with the ventricular surface it seems that this structure, which we have named the transverse cerebellar sling, is composed of glial processes, although it was not immunoreactive for S-100 or glial fibrillary acidic protein. The transient appearance of this sling encircling the posterior cerebellum is suggestive of a role in prenatal cerebellar morphogenesis.