"The legacy of thalidomide" - A multidisciplinary meeting held at the University of York, United Kingdom, on September 30, 2016 : A multidisciplinary meeting held at the University of York, UK on September 30, 2016

BACKGROUND: Between 1957 and 1962 thalidomide was used as a nonaddictive, nonbarbiturate sedative that also was successful in relieving the symptoms of morning sickness in early pregnancy. Infamously, thousands of babies were subsequently born with severe birth defects. The drug is used again, today, to successfully treat leprosy, and tragically, there is a new generation of thalidomide damaged children in Brazil. While the outward damage in babies has been documented, the effects of the damage upon the survivors as they grow up, the lifestyle changes and adaptations required to be made, as well as studies into ageing in survivors, has received little attention and remains understudied. METHODS: A unique multidisciplinary meeting was organized at the University of York bringing together thalidomide survivors, clinicians, scientists, historians, and social scientists to discuss the past, the current and the future implications of thalidomide. RESULTS: There is still much to learn from thalidomide, from its complex history and ongoing impact on peoples' lives today, to understanding its mechanism/s to aid future drug safety, to help identify new drugs retaining clinical benefit without the risk of causing embryopathy. CONCLUSION: For thalidomide survivors, the original impairments caused by the drug are compounded by the consequences of a lifetime of living with a rare disability, and early onset age-related health problems. This has profound implications for their quality of life and need for health and social care services. It is vital that these issues are addressed in research, and in clinical practice if thalidomide survivors are to "age well". Birth Defects Research 109:296-299, 2017. © 2017 Wiley Periodicals, Inc

Thalidomide Embryopathy - Orthopaedic aspects. Degenerative changes and quality of life at age 45

In the late 1950s and early 1960s, a sudden peak was seen among children with different, severe malformations, caused by the intake of the drug thalidomide during pregnancy. Among other featured malformations, so-called thalidomide embryopathy (TE), the most obvious were seen in the extremities. In this thesis, orthopaedic problems, physical function and quality of life in a cohort of survivors with TE in Sweden, around 45 years of age, were investigated. The study group of 31 individuals with TE underwent a clinical examination, computed tomography (CT) of the pelvis and lower limbs (Study I) and MRI of the cervical spine (Study II) and answered several questionnaires (Studies I, III, IV). For evaluations of function, the “Disability in Shoulder Arm and Hand” (DASH) and “Rheumatoid Arthritis Outcome Score” (RAOS) were used (Study I). Health-related quality of life was evaluated by the Short Form-36 (SF-36) and Euro Qol-5 Dimensions (EQ-5D) (Study III) and the level of independence was evaluated by a modified General Function Score (GFS) and WHO questionnaire (Study IV). The individuals with TE had a number of different malformations in the extremities. Five individuals were identified as having a proximal femoral focal deficiency (PFFD). The whole group had a high prevalence of moderate osteoarthritis in their hip and knee joints and reported greater disability in terms of upper limb function compared with the general population. The individuals with PFFD reported significantly poorer lower extremity function than the rest of the group (Study I). Individuals with TE demonstrated a high frequency of degenerative changes in the cervical spine compared with a control group (Study II). Individuals with TE reported a reduction in physical quality of life measured by both the SF-36, i.e. the Physical Composite Summary Score (PCS), and EQ-5D. Their mental quality of life was not affected, when measured by either the SF-36 Mental Composite Summary Score (MCS) or the EQ-5D. A relationship between low PCS and the number of extremities involved, as well as with the DASH score and the RAOS’s pain subscore (Study III), was observed. Individuals with TE generally demonstrated a high level of independence, as the majority were employed and participated in physical activities (Study IV). In conclusion, middle-aged individuals with TE demonstrated an increased risk of degenerative changes in both larger joints and the cervical spine. Individuals with PFFD were most affected in terms of physical function, daily activities and quality of life. Despite a decrease in physical function in the overall group, their mental quality of life was not affected

Physical function measured by modified GFS and ADL for the total study group individuals with PFFD and without PFFD.

<p>Comparison calculated between individuals with PFFD and without PFFD. mean (SD)/range, n(%).</p

The need for different types of aid, disability adjustments and assistance to manage locomotion and daily activities in the total of 31 individuals with TE.

<p>The need for different types of aid, disability adjustments and assistance to manage locomotion and daily activities in the total of 31 individuals with TE.</p

Middle-aged individuals with thalidomide embryopathy have undergone few surgical limb procedures and demonstrate a high degree of physical independence - Fig 1

<p>Time needed for ADL for Group A (TE individuals with a disability-adjusted home and/or workplace and/or a personal assistant), (n = 12) and Group B (no need for disability adjustment and/or personal assistant) (n = 19). Significantly more individuals in Group A stated that they needed longer for ADL in the morning than those in Group B (p = 0.009).</p

Comparison between the total TE group (n = 31), individuals with PFFD and without PFFD regarding physical activity level at work and in spare time according to WHO questionnaire n(%).

<p>Comparison between the total TE group (n = 31), individuals with PFFD and without PFFD regarding physical activity level at work and in spare time according to WHO questionnaire n(%).</p

Surgeries performed on the five persons with proximal focal femoral deficiency (PFFD).

<p>Surgeries performed on the five persons with proximal focal femoral deficiency (PFFD).</p

Degenerative Changes in the Cervical Spine Are More Common in Middle-Aged Individuals with Thalidomide Embryopathy than in Healthy Controls.

BACKGROUND:Thalidomide was used as a sedative drug for pregnant women in the 1950-60:s and resulted in children born with thalidomide embryopathy (TE), including upper limb malformations. These may alter the motion pattern of the cervical spine by the use of head/shoulder and mouth grip. AIMS:To compare degenerative changes in the cervical spine in TE individuals with healthy controls (CTR). METHODS AND PROCEDURES:Twenty-seven middle-aged TE individuals and 27 age- and gender-matched CTR were examined by cervical spine MRI. The presence of malformations, disc herniation(s), osteophytes, nerve and medullary compression and the degree of disc degeneration (DD) were evaluated. OUTCOMES AND RESULTS:Significantly higher degree of DD was seen in the TE group compared with the controls (p<0.001). Similar frequencies of disc herniation and disc space narrowing were observed in the two groups, but more foraminal narrowing was seen in the TE group (p = 0.002). DD was observed relatively frequently at all cervical levels in the TE group, however, mainly at the two lower levels in the CTR. CONCLUSIONS AND IMPLICATIONS:Middle-aged individuals with TE have a higher frequency of degenerative changes in the cervical spine than controls, possibly caused by an altered load on the cervical spine

MRI image of cervical spine in TE.

<p>MRI of the cervical spine for one of the TE patients where moderate disc degeneration was seen at C3-4, C4-5 and C5-6 level (A). Foraminal narrowing with nerve compromise can be seen here at level C5-6 on the right side (B and enlargement C, with arrow pointing at the disc/bulge/nerve compromise).</p