14800-DvRappard

163 Discussion, summary and future perspectives 10 DISCUSSION AND SUMMARY Clinical aspects In order for patients to be diagnosed in time for HCT, it is of great importance that the different possible presenting symptoms are recognized by physicians. We described in chapter 3 that in juvenile and adult onset patients, psychiatric symptoms can precede neurological signs. The combination of an initially normal child with a clear change of behavior together with mild cognitive deterioration should prompt diagnostic evaluation for neurometabolic disorders. Early and correct diagnosis is not only essential to allow for HCT, a possible life saving treatment, but also for appropriate palliative treatment and genetic counseling. In addition, only through correct (and timely) diagnosis, siblings can be diagnosed while they are still presymptomatic and thus ideal candidates for HCT. Treatment MLD patients not treated with HCT invariably develop spasticity and often also a dyskinetic movement disorder, which is painful in many patients and can hamper daily care. Baclofen is a GABA-agonist that inhibits neural transmission at the spinal cord and is therefore frequently used to improve spasticity. 1 Intrathecal baclofen treatment (IBT) allows specific drug administration to tissues that are most responsible for spasticity with little exposure to the brain, thereby reducing side effects. 2 In chapter 4 we studied ITB treatment in MLD patients to reduce spasticity and compared this to patients with spastic cerebral palsy (SCP). We showed that ITB is a safe and feasible therapy to improve comfort and daily care in MLD patients with both spastic and dyskinetic movement impairments. The treatment in MLD patients is comparable to SCP patients regarding baclofen dosage and complications. We recommend ITB early in the disease course for patients in whom oral baclofen no longer sufficiently reduces painful spasms and when spasticity hinders daily care. In chapter 5 , we compared our transplanted patients with patients no longer eligible for HCT, diagnosed in the same time period. We showed that HCT is a safe procedure, with no treatment relatedmortality (TRM) in this study. 3 HCT has proven to be able to stop the disease once performed in pre- or early symptomatic patients with the juvenile or adult onset type. For more advanced and late-infantile patients, HCT at best delays disease progression. Together with our study, two other large studies compared the effect of HCT in MLD patients to non-transplanted patients. 4,5 Boucher et al report a TRM of 23%, which they partially explain by the fact that part of their cohort was transplanted years ago when HCT was riskier due to less advanced protocols and techniques. In consensus