Hannu Heiskala

Epidemiology and histopathology of Hodgkin's disease in Finland

All cases diagnosed as malignant lymphoma in Finland from 1961 to 1964 were histologically re‐examined and re‐classified. The original material consisted of 314 cases diagnosed as Hodgkins disease, but after re‐examination only 207 cases were regarded to be Hodgkins disease. The age specific incidence curve of Hodgkins disease both before and after re‐examination was bimodal. The second peak was much lower in the re‐examined series because of the exclusion of many non‐Hodgkins lymphomas. The bimodality was more clear in females. Hodgkins disease was more common in urban than in rural areas. This difference was greatest in young adulthood. Nodular sclerosis, (NS) was the most common histologic type (53% in males, 83% in females). Its age specific incidence curve was bimodal with a high young adulthood peak. It was more common in urban areas and occurred there at younger age than in rural areas. Lymphocytic predominance, mixed cellularity and lymphocytic depletion groups had the highest incidence rates in old age. Hodgkins disease seems to be a heterogeneous group composed of two or more entities, one of which is the young adult disease, probably the commonest entity in western countries especially in urban areas. The entities do not seem to correspond strictly to the present histologic types. However, most cases of NS probably represent young adult disease and most patients with young adult disease have NS.

West syndrome: individualized ACTH therapy

Individualized ACTH treatment of the West syndrome (WS) was assessed in a prospective multicenter study, in which each patients dosage was increased stepwise according to response. Our series included six patients with cryptogenic and 24 with symptomatic infantile spasms. During the treatment period the total ACTH dose ranged from 58 to 373 i.u./kg. In the cryptogenic group one patient responded to pre-ACTH pyridoxine and four to the lowest dosage of ACTH (3 i.u./kg daily) with cessation of spasms and good outcome; one patient needed the highest dosage (12 i.u./kg daily) for cessation of seizures and became developmentally retarded. In the symptomatic group, 21 of the 24 patients needed 6-12 i.u./kg daily; 12 became seizure-free or having infrequent non-IS fits. Complications such as arterial hypertension, cerebral ventricle dilatation, cardiac hypertrophy, and prolonged adrenocortical hyporesponsiveness were related to the dose. The individualization provides all the benefits of ACTH treatment with minimal side effects and cost.

Neurological impairments and sleep–wake behaviour among the mentally retarded

The objective of the present study was to evaluate the relationship between the sleep–wake behaviour and neurological impairments among mentally retarded people. The sleep–wake behaviour of 293 mentally retarded subjects living in a rehabilitation center was studied by a standardized observation protocol carried out by trained staff members. The protocol consisted of brief check‐ups of the subjects’ sleep–wake status at 20‐min intervals for five randomly chosen 24‐h periods during 4 months. From the raw data five sleep–wake behaviour variables were formed. The data concerning the subject characteristics (age, body mass index (BMI), gender, degree of mental retardation, presence of locomotor disability, that of epilepsy, blindness or deafness and the usage of psychotropic medications) were collected from the medical records. Two main findings emerged: (1) severe locomotor disablity, blindness and active epilepsy were found to be independent predictors of increased daytime sleep and increased number of wake–sleep transitions and (2) the subjects with a combination of two or all three of these impairments had a significantly more fragmented and abnormally distributed sleep than those with none or milder forms of these impairments. Age, BMI, degree of mental retardation and the studied medications played a minor role in the sleep disturbances of the study population. Finally, deafness was not found to be associated with any of the measured sleep–wake variables.

No evidence for extraocular light induced phase shifting of human melatonin, cortisol and thyrotropin rhythms

The view that light affects the mammalian circadian clock only through the eyes was recently challenged by a study in which the phases of human circadian rhythms were shifted by extraocular light exposure. This finding has not been confirmed, however. We studied the effects of light exposure (3 h, broad spectrum fluorescent white light, 13 000 lux) on abdomen and chest on the circadian rhythms of serum melatonin, cortisol and thyrotropin in six subjects. The protocol consisted of two 3-day sessions in a dimly lit (< 10 lux) experimental unit. In both sessions hourly serum samples were collected for hormone analysis on days 1 and 3. The skin light exposure was delivered on day 2 from 22.00 to 01.00 h in one of the two sessions in a randomized order. In both sessions all three rhythms tended to delay, presumably due to the endogenous circadian cycle length being slightly longer than 24 h. However, the phase shifts did not differ significantly between the sessions. Thus, the present study does not support the existence of extraocular photic regulation of the circadian rhythms in humans.

CSF ACTH and β-endorphin in infants with West syndrome and ACTH therapy

Abstract Corticotrophin (adrenocorticotropic hormone, ACTH) and β-endorphin levels of the cerebrospinal fluid (CSF) were determined in 16 infants with the West syndrome during individualized ACTH treatment. Prior to treatment, the levels of CSF ACTH were significantly higher in infants with cryptogenic spasms, normal perinatal events, or normal development than in infants with symptomatic spasms or delayed development. The CSF β-endorphin levels did not differ among the groups. At response, the infants could be divided into three groups: (1) short-course, low-dose responders with a substantial CSF ACTH decline, (2) long-course, high-dose responders with no such effect (but with a tendency towards an upward incline), and (3) non-responders with no significant CSF ACTH changes. The changes in CSF β-endorphin were somewhat similar to the changes in CSF ACTH, but the greater variability did not allow statistical significance.

Sleep fragmentation in mentally retarded people decreases with increasing daylength in spring.

We studied the sleep–wake behavior of mentally retarded people from late winter to early summer at 60°N. During this time the daylength increased 8 h 51 min. The data were collected by observing the sleep–wake status of 293 subjects at 20-min intervals for five randomized 24h periods (=recording days). The intervals during which the individual recording days of the same order (1st, 2nd, etc.) were carried out, were called recording periods. Consequently, there were five recording periods, each containing 293 individual recording days. Even though there was overlap among the recording periods, the median daylength from one period to another increased approximately by 100 min. In the initial statistical analysis, the number of wake–sleep transitions was found to differ significantly among the five recording periods (Friedman test, p<0.001). The mean ranks in the Friedman test suggested that the number of wake–sleep transitions was highest during the 1st and lowest during the 5th recording period. In further statistical analyses using a program for mixed effects regression analysis (mixor 2.0) it was found that the increase in daylength during the study period was associated with a simultaneous decrease of approximately 0.5 wake–sleep transitions in the whole study population (p<0.001). The decrease in the number of wake–sleep transitions was significant only in the subgroups of subjects with a daylength change of more than 350 min between the 1st and 5th recording days (Wilcoxon tests, p<0.005). This suggests that after a marked prolongation of the natural photoperiod, the reduction in sleep episodes was more probable than after smaller changes in daylength. It is concluded that the sleep of mentally retarded people living in a rehabilitation center at a northern latitude is more fragmented in winter than in early summer and that the change is related probably to the simultaneous increase in the length of the natural photoperiod. The sleep quality of persons living in institutional settings might be improved by increasing the intensity and/or duration of daily artificial light exposure during the darker seasons.

Brain perfusion SPECT in children with frequent fits

We studied 14 children with frequent fits using 99mTc-HM-PAO single photon emission computed tomography (SPECT). There were 11 patients with partial secondary generalized epilepsy (PSGE) and 3 with Lennox-Gastaut syndrome (LGS). The typical regional cerebral blood flow (rCBF) finding in PSGE was a single area of abnormally low perfused cortex, and that in LGS, multiple hypoperfused areas. Clinically, the LGS patients were more severely affected. SPECT was more sensitive in detecting abnormalities than EEG, CT or MRI. Extensive impairment of rCBF may thus indicate unfavourable development of intellectual performance and poor seizure control.

Subjects With Intellectual Disability and Familial Need for Full-Time Special Education Show Regional Brain Alterations: A Voxel-Based Morphometry Study

Subjects attending full-time special education (SE) often have multifactorial background for their cognitive impairment, and brain MRI may show nonspecific changes. As voxel-based morphometry reveals regional volume differences, we applied this method to 119 subjects with cognitive impairments and familial need for full-time SE—graded into three levels from specific disorders of cognitive processes (level 1) to intellectual disability (IQ <70; level 3)—and to 43 age-matched controls attending mainstream education (level 0). Subjects in SE groups had smaller global brain white matter (WM), cerebrospinal fluid, and total brain volume than controls. Compared with controls, subjects with intellectual disabilities in SE level 3 showed greater regional gray matter volumes bilaterally in the ventral and dorsal anterior cingulate cortex and smaller regional gray matter volumes in the left thalamus and cerebellar hemisphere. Further, they had greater WM volume in the left frontoparietal region and smaller WM volumes in the posterior limbs of the internal capsules. Subjects in SE level 1 and 2 groups showed the same tendency, but the results were nonsignificant. In conclusion, compared with controls, subjects with intellectual disabilities showed in voxel-based morphometry analysis several regional brain alterations.

Brain Magnetic Resonance Imaging of Siblings from Families with Two or More Children with Learning or Intellectual Disabilities and Need for Full-Time Special Education

Background: Several factors are involved in determining a childs need for special education (SE). Thus, the value of brain magnetic resonance imaging (MRI) for subjects with learning and intellectual disabilities is uncertain. Purpose: To evaluate the usefulness of MRI in the diagnostic process of siblings with learning and intellectual disabilities and need for full-time SE. Material and Methods: Altogether, 119 siblings (mean age 11.9 years) from families in which two or more children attended/had previously attended full-time SE underwent prospective brain MRI. SE grouping included three levels, from specific learning disabilities (level 1) to global intellectual disabilities (level 3). Forty-three controls (level 0, mean age 12.0 years) attended mainstream education groups. Signal intensity and structural abnormalities were analyzed, and areas of the cerebrum, posterior fossa, corpus callosum, vermis and brain stem, and diameters of the corpus callosum were measured. In analyses, all area measurements were calculated in proportion to the total inner skull area. Results: Abnormal finding in MRI was more common for siblings (n=62; 52%) in SE (58% for level 3; 49% for level 2; 35% for level 1) than for controls (n=13; 16%). The siblings showed enlarged supra- (P<0.001) and infratentorial (P=0.015) cerebrospinal fluid (CSF) spaces and mild corpus callosum abnormalities (P=0.003) compared to controls. Siblings in SE had smaller inner skull area than controls (P<0.001). Further, the relative area of the mesencephalon (P=0.027) and the diameter of the body of the corpus callosum (P=0.015) were significantly smaller than in controls. In binary logistic regression analysis, enlarged supratentorial CSF spaces increased the probability of SE (odds ratio 4.2; P=0.023). Conclusion: Subjects with learning and intellectual disabilities commonly have more MRI findings than controls. Enlarged supratentorial CSF spaces were a frequent finding in siblings in full-time SE.

Childhood growth and development associated with need for full-time special education at school age

OBJECTIVE To explore how growth measurements and attainment of developmental milestones in early childhood reflect the need for full-time special education (SE). METHODS After stratification in this population-based study, 900 pupils in full-time SE groups (age-range 7-16 years, mean 12 years 8 months) at three levels and 301 pupils in mainstream education (age-range 7-16, mean 12 years 9 months) provided data on height and weight from birth to age 7 years and head circumference to age 1 year. Developmental screening was evaluated from age 1 month to 48 months. Statistical methods included a general linear model (growth measurements), binary logistic regression analysis (odds ratios for growth), and multinomial logistic regression analysis (odds ratios for developmental milestones). RESULTS At 1 year, a 1 standard deviation score (SDS) decrease in height raised the probability of SE placement by 40%, and a 1 SDS decrease in head size by 28%. In developmental screening, during the first months of life the gross motor milestones, especially head support, differentiated the children at levels 0-3. Thereafter, the fine motor milestones and those related to speech and social skills became more important. CONCLUSION Children whose growth is mildly impaired, though in the normal range, and who fail to attain certain developmental milestones have an increased probability for SE and thus a need for special attention when toddlers age. Similar to the growth curves, these children seem to have consistent developmental curves (patterns).