Competencia científica

Formal neuropsychological assessment was performed by designated research neuropsychologists, Ms Claire Chapman, Ms Louise Parry and Ms Leasha Liliywhite from the Neurosciences Unit at the Wolfson Centre, Great Ormond Street Hospital for Children and the Institute of Child Health, London.

Different aspects of cognitive function including intelligence, memory and learning, language, and academic attainments were assessed using the following tests as described by Vargha-Khadem et al and Christie et al (Christie et al. 1994;Christie et al. 1995;Vargha-Khadem F. et al. 1992).

a. Intelligence The age-appropriate Wechsier Intelligence scales were administered to evaluate intellectual ability.

i) The Wechsier Intelligence Scale for Children - Third edition UK (W ISC-III)

for children aged 6 years to 16 years and 11 months (Wechsier 1992)

11) The Wechsier Adult Intelligence Scale - Revised UK (W A IS-R ) for patients

aged 17 years and over (Wechsier 1986)

The Wechsier Scales of Intelligence provide verbal, performance and full scale intelligence quotients (IQ). The average IQ is 100 (range 90 to 110). Mild learning difficulty was graded as IQ of 80 to 89, moderate learning difficulty IQ 70 to 79 and severe learning difficulty IQ <70 (<-2SD from the mean). Nineteen of the 28 children were assessed using the W iS C -lll and the 9 older patients using the W AIS-R. Five subtests are used to calculate the VIQ and the PIQ which have a mean of 100 and a standard deviation of 15. The scaled scores for each subtest yield standard scores with a mean of 10 and standard deviation of 3 (range 1 -19).

b. Memory and Learning.

(I) The Wechsier Memory Scale (Wechsier 1945), with age corrections for children, was used to assess memory and learning. The overall memory quotient, was calculated according to the WMS manual. In addition, two subtests were selected to provide measures of immediate and delayed recall for verbal and visual

information (Logical Memory and Visual Reproduction), and one subtest to provide a measure of verbal learning and delayed recall (Paired Associate Learning).

Logical Memory. For children over the age of 12 years (n=20) the two standard

Wechsier stories constituting the Logical Memory subtest (Form 1) were used, containing 24 and 22 units of information, respectively. For children below the age of 12 years (n=8), two children’s stories developed by Taylor (Kimura & McGlone 1979) were substituted for the standard Wechsier stories. Each contained 18 units of information. Whichever set was used, recall of each story was obtained immediately after its presentation and an average score was calculated for the pair. Following a 90 minute interval filled with unrelated tasks, delayed recall of each story was obtained and an average score again calculated.

Paired Associate Learning. This subtest was administered as described in the

WMS manual and scored for immediate recall after each of the three presentations of the 10 paired associates. The set of 10 pairs consists of six pairs of related items (e.g. up-down) and four pairs of unrelated items (e.g. cabbage-pen). The related and unrelated items were scored separately. Recall was also measured after a 90 minute filled delay. Delayed recall was scored out of 10.

Visual Reproduction. The immediate reproduction of geometric designs was

scored as described in the WMS manual. In addition, following a 40 minute delay filled with other tasks, participants were again asked to draw the geometeric designs from memory.

(ii) The Children’s Auditory Verbal Learning Test -II Ed (CAVLT-II) (Talley 1993) was administered to provide measures of immediate memory span, level of learning, interference with learning, recognition accuracy, and immediate and delayed recall. The test Involves a list of 16 words (List A) being presented five times for immediate recall. An interference list of 16 words (List B) is then presented for immediate recall before the child is asked to recall the original list (List A). The child is also asked to recall the words (List A) after a 20 minute delay. This test provides standard scores which have a mean of 100 and a standard deviation of 15.

c. Language.

(i) The British Picture Vocabulary Scale (BPVS) (Dunn 1982) was administered

to provide a measure of receptive vocabulary for words and concepts. This test does not require the child to read, write, or speak as he or she is instructed to point to one of four pictures that best matches the word spoken by the examiner. Raw scores are then converted to standard scores which have a mean of 100 and standard deviation of 15.

(ii) The Wechsier Objective Language Dimensions (WOLD) (Wechsier 1996a) comprises several subtests. The Listening Comprehension subtest examines the child’s understanding of orally presented words and passages. In the Words subtest, the child is presented with a page of four pictures and is instructed to point to the picture that corresponds to the word. For the Passages subtest, a related picture is shown and the participant is asked to answer questions relating to the passages heard. The Oral Expression subtest assesses the ability to describe a target word, describe a scene, give directions and explain steps. Scores are converted to age-graded standard scores which have a mean of 100 and a standard deviation of 15. The Written Expression subtest of the WOLD was not administered.

d. Academic Attainments.

(\)The Wechsier Objective Reading Dimensions (WORD) (Wechsier 1993)

comprises three subtests: Basic Reading, for which the child has to read the words of increasing difficulty; Spelling, which requires the child to write the spelling of verbally presented words of increasing difficulty; and Reading Comprehension, in which the child has to read a passage aloud and answer questions on it. Scores are converted to age-graded standard scores with a mean of 100 and a SD of 15.

(Ii) The Wechsier Objective Numerical Dimensions (WOND) (Wechsier 1996b) comprises two subtests: Mathematical Reasoning which taps the ability to reason mathematically, and Numerical Operations which assesses the ability to write dictated numerals and solve calculation problems involving basic operations. Scores are converted to age-graded standard scores which have a mean of 100 and a SD of 15.

Section 4.2. Results

Ten (25%) of the 40 patients had clinical and/ or MRI evidence of CNS

involvement. The neurological abnormalities and relevant MRI appearances in these 10 patients are summarised in Table 4.1. A detailed description and discussion of MRI findings is given in Chapter 5.

Clinical CNS abnormalities included ataxia and incoordination, psychological problems and learning difficulty reported by parents and /or teachers. These problems were not evident at diagnosis of LCH, and were unusual during the “acute” phase of the illness. The time from diagnosis of LCH to the first symptom suggestive of CNS damage ranged from 8 to 240 months (mean 112 months, median 108 months). Only 1 child presented with severe behavioural problems within the first year of diagnosis of LCH and was later noted to have learning difficulty. All the rest of the patients developed symptoms/ signs of CNS damage as “late” sequelae.