Multimodality evoked potentials in progression of metachromatic leukodystrophy

Takakura, Hiroki; Nakano, C; Kasagi, Shigeto; Takashima, Sachio; Takeshita, Kenzo

doi:10.1016/s0387-7604(85)80141-8

Cited by 12 publications

(3 citation statements)

References 13 publications

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“…Furthermore, our research group demonstrated that the central components of the auditory evoked potentials in taiep rats are significantly altered in their morphology and with delayed central components that are due to the demyelination process with a similar response in a Mexican patient suffering from H-ABC [8]. These results support that, besides the structural damages in TUBB4A and the corresponding hypomyelination of the central white matter, the clinical neurophysiology evaluation can be a valuable tool to determine the integrity of myelin sheaths in human patients suffering from this tubulinopathy and it could be useful in other leukodystrophies or leukoencephalopathies [28,29]. Consequently, the availability of the taiep rat allows the evaluation of other neurophysiological evoked responses such as SSEPs and MEPs and compare them with wild type rats, we also compare healthy children with respect to those affected of H-ABC.…”

Section: Discussionsupporting

confidence: 66%

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

Eguibar,

Cortes,

Hernandez

et al. 2024

PLoS ONE

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The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.

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Section: Discussionsupporting

confidence: 66%

4-aminopyridine improves evoked potentials and ambulation in the taiep rat: A model of hypomyelination with atrophy of basal ganglia and cerebellum

Eguibar,

Cortes,

Hernandez

et al. 2024

PLoS ONE

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“…Several studies have addressed the electrophysiological findings of peripheral neuropathy in MLD and their progression over time. A cohort study of 40 MLD patients from India and three case reports found a length dependent neuropathy, in which sensory nerve conduction velocity (NCV) was delayed earlier and more severely than motor NCV [19, 22, 27, 34]. Conversely, the studies of Krishnan et al [35] and Lütschg [36] found that the motor NCV was more affected than the sensory NCV (39 and four MLD patients respectively) .…”

Section: The Clinical Spectrum Of Metachromatic Leukodystrophymentioning

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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“…Other diseases affecting myelin, such as adrenoleukodystrophy, 29 adrenomyeloneuropathy, 92 metachromatic leukodystrophy, 90 and Pelizaeus-Merzbacher disease, 18 also produce SEP abnormalities. In adrenoleukodystrophy and adrenomyeloneuropathy, SEPs may be abnormal in asymptomatic heterozygotes.…”

Section: Brain and Brainstemmentioning

confidence: 99%