Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation

Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.

Section: Discussionmentioning

confidence: 99%

Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature

Hosson

Warrenburg

Preijers

et al. 2010

“…Practice effects regarding the different tests are not thought to be strong enough to influence the results, and when dementia is present, no practice effect is detectable. 20 Generally, patients with MLD tend to have higher scores for Verbal IQ than for performance IQ. 9,11,12 The same reference values for IQ in the WAIS tests were kept over time irrespective of the ageing of the patients, to give a representative view of the patients' development over time.…”

Section: Neuropsychologymentioning

confidence: 98%

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Solders

Martin

Andersson

et al. 2014

In metachromatic leukodystrophy (MLD), the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) leads to demyelination in the central and peripheral nervous system and ultimately to death. Allogeneic hematopoietic SCT (HSCT) is currently the only treatment for adult and late-onset juvenile MLD, although it is still in question because of insufficient follow-up. We wanted to determine whether HSCT could halt the progression of adult and late-onset juvenile MLD. Four treated unrelated patients and three untreated siblings were included in the study, and followed regularly for up to 18 years after transplantation. The patients were assessed from clinical examination, ARSA enzyme levels, magnetic resonance imaging of the brain and neuropsychological and neurophysiological tests. In the treated patients, ARSA levels were normal up to 18 years after transplantation. The parameters evaluated stabilized and remained stable after a latency period of 12-24 months. Two patients live normal lives, partially in a protected environment. The other two patients stabilized at a low cognitive and functional level. One of the controls is demented, one is in a vegetative state and one died. We conclude that, in comparison with their untreated siblings, HSCT halted the progression of the disease in our treated patients.

“…3 Most cases of MLD treated with BMT have hitherto been infantile and early juvenile forms and the best results have been obtained in the presymptomatic cases. 7,12,13 In slowly progressing late juvenile cases with only minor symptoms, a stable clinical, neurophysiological and neuropsychological state has been reported after BMT. 4,14 However, deterioration may continue for up to 2 years after BMT and mental function stabilizes at a lower level than the baseline IQ.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, no practice effects are seen when dementia is present. 7 The neuropsychological assessments before the transplantation showed progressive cognitive impairments in executive functions, such as poor planning ability, distractibility and also an early decline in visuospatial-constructive and spatial memory tasks. FSIQ was 52, with slightly better values for VIQ (61) than for PIQ (52).…”

Section: Neuropsychological Assessmentmentioning

confidence: 98%

Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy

Solders¹,

Celsing²,

Hagenfeldt³

et al. 1998

Summary:A 28-year-old woman with a 4 year history of slowly progressing 'frontal dementia' was diagnosed as having adult metachromatic leukodystrophy and was followed for 4 years after bone marrow transplantation (BMT). MRI, neurophysiological tests (EEG, ENeG, VEP, SEP and BAEP) and neuropsychological assessment were performed before, and repeatedly after BMT. MRI showed symmetrical white matter lesions in the frontal and parieto-occipital lobes and in the corpus callosum. EEG showed frontal and temporal slow wave abnormalities and nerve conduction was slow. Neuropsychological tests showed cognitive impairment in executive functions, decline in visuospatial-constructive and spatial memory tasks and disorganized thinking. IQ was low (52), with slightly better values for verbal IQ than for performance IQ. After BMT, the patient was followed for 4 years. Clear improvements were seen in EEG, in peripheral nerve conduction and in neuropsychological tests (especially in verbal IQ). MRI findings were unchanged. We believe that the improvement in our patient resulted from the bone marrow transplantation. Keywords: metachromatic leukodystrophy; bone marrow transplantationIn metachromatic leukodystrophy (MLD), the accumulation of galactosyl sulphatide in lysosomes, due to an inherited deficiency of arylsulphatase A, causes demyelination in the central and peripheral nervous systems. Clinical symptoms vary. Depending on the age at onset of clinical symptoms and on the course of the disease, MLD is classified as late infantile (6 months to 2 years), early juvenile (4 to 6 years), late juvenile (6 to 16 years) and adult (Ͼ16 years) types. In adult MLD, psychiatric symptoms dominate with a change in personality, poor school or job performance and emotional lability. Disorganized thinking and impairment of memory functions then occur and hypomania/depression Correspondence: Dr G Solders, Department of Neurology, Huddinge Hospital, S-141 86 Sweden Received 27 April 1998; accepted 15 July 1998 or psychosis is common. 1 Adult MLD may develop as a schizophrenic disorder 2 or it may present as polyneuropathy. 3 Bone marrow transplantation (BMT) is recommended for presymptomatic cases in infants and children with a sibling with MLD and for early cases of juvenile MLD. BMT has been performed in only a few cases of adult MLD. 4 Case report and methodsA 28-year-old woman with a 4 year history of slowly progressing 'frontal dementia' was diagnosed as having adult metachromatic leukodystrophy. She had previously been healthy, except for slight hypothyroidism, for which she had been treated. She had completed 12 years of school with excellent grades and had started university studies. At 24 years old, she gave birth to twins. After that, her parents noted a slow change in personality, with increasing difficulties in daily living and in caring for her children. Dyscalculia and inertia were observed. She appeared depressed for a while and then developed a schizophreniform state and was referred to a psychiatric clinic. She became progressi...