Intrathecal baclofen in metachromatic leukodystrophy

Veldt, Nikki van der; Rappard, Diane F. van; Pol, Laura A. van de; Knaap, Marjo S. van der; Ouwerkerk, W. J. R. van; Becher, Jules G.; Wolf, Nicole I.; Buizer, Annemieke I.

doi:10.1111/dmcn.13919

Cited by 11 publications

(12 citation statements)

References 15 publications

(30 reference statements)

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“…Still, no effective treatment has been found for symptomatic MLD patients [3, 79]. For these patients, symptomatic treatments as botulinum toxin or intrathecal administration of baclofen can be helpful to treat spasticity [80]. The following paragraphs provide a summary of the results of preclinical studies and clinical trials targeting HCT, gene therapy, enzyme replacement therapy (ERT), and warfarin administration, with emphasis on the treatment effects on the PNS.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Beerepoot

Nierkens

Boelens

et al. 2019

Orphanet J Rare Dis

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Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies.

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Section: Therapeutic Approachesmentioning

confidence: 99%

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Beerepoot

Nierkens

Boelens

et al. 2019

Orphanet J Rare Dis

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“…Intrathecal baclofen has been widely used for spasticity management in children, mostly with cerebral palsy and brain injury, although some recent studies have shown promising effects of baclofen pumps on tone in patients with lysosomal storage deficiencies such as metachromatic leukodystrophy, 9,10 mucopolysaccharidosis type II, 11 or Gaucher disease. 12 It allows for the treatment of spasticity with fewer side effects such as liver toxicity, sedation, or secretion management.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] A handful of publications have discussed the effect of baclofen pumps in patients with neurodegenerative metabolic disease. [9][10][11][12] There has been no literature about using intrathecal baclofen in cases of Niemann-Pick. An informal survey on the Pediatric Intrathecal Baclofen Pump Network of 200 baclofen pump providers across North America and Europe also yielded no known cases of using intrathecal baclofen for Niemann-Pick.…”

Section: Introductionmentioning

confidence: 99%

The Palliative Use of Intrathecal Baclofen in Niemann-Pick Disease Type C

et al. 2019

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Niemann-Pick disease type C is a rare progressive genetic disorder that leads to the abnormal accumulation of lipids within various tissues of the body, including brain tissue and liver. There is a rapid progression of the disease, resulting in severe disability in only a few years after the first symptoms, and survival is not much longer. Spasticity, dystonia, and chronic pain are common findings that severely impact quality of life in these patients. Analgesic management with traditional pain medications is not always effective, and the risk for secondary effects in medically complex patients is high. Liver function is also a limiting factor in these patients. This is a case report of a boy with advanced Niemann-Pick disease type C with developmental regression, cataplexia, and seizures. His severe spasticity made positioning and care difficult, and intense pain required multiple hospitalizations. He had unsuccessfully trialed multiple drugs. An intrathecal baclofen pump was placed without surgical complications and resulted in positive clinical effects. Baclofen pumps have classically been used for spasticity management in adults and children with nonprogressive diseases such as cerebral palsy or spinal cord injury with relatively long life expectancies. In adults, they have been used in patients with multiple sclerosis; however, use in pediatric neurodegenerative diseases has scarcely been reported. The use of intrathecal baclofen in palliative settings might provide an additional resource to provide comfort and quality of life for children with neurodegenerative diseases not only at end-of-life stages but also earlier on.

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“…Hence, many of these drug-refractory patients experience significant symptomatic improvement after baclofen intrathecal infusion pump or deep brain stimulation (DBS) following an appropriate selection process. Intrathecal baclofen pump has been indicated in several patients with spasticity or severe dystonia and progressive IEMs, in some cases for palliative purposes, for example: Niemann Pick disease type C (153), Sjögren-Larsson syndrome (154), Metachromatic leukodystrophy (155), and Gaucher disease type 2 (156). Regarding DBS, Supplementary Table 4 describes the role and evidence of DBS in selected IEMs and childhoodonset MD.…”

Section: Step 5 Treatment Of Pediatric Metabolic Movement Disordersmentioning

confidence: 99%

A Proposed Diagnostic Algorithm for Inborn Errors of Metabolism Presenting With Movements Disorders

Ortigoza‐Escobar

2020

Front. Neurol.

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Intrathecal baclofen in metachromatic leukodystrophy

Cited by 11 publications

References 15 publications

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

The Palliative Use of Intrathecal Baclofen in Niemann-Pick Disease Type C

A Proposed Diagnostic Algorithm for Inborn Errors of Metabolism Presenting With Movements Disorders

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