Head trauma can initiate the onset of adreno-leukodystrophy

Raymond, Gerald V.; Seidman, Roberta; Monteith, Teshamae; Kolodny, Edwin H.; Sathe, Swati; Mahmood, Asif; Powers, James M.

doi:10.1016/j.jns.2009.11.005

Cited by 74 publications

(72 citation statements)

References 17 publications

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Section: Reportmentioning

confidence: 99%

“…By then, he exhibited a pronounced cogwheel phenomenon, unresponsive deep tendon reflexes, and dystonic contractures, but was able to manipulate his wheelchair. Deep brain stimulation (DBS) was considered at the request of the patient and his family (Vidailhet et al 2005); the benefits and risks (i.e., exacerbation of demyelination with external trauma) (Raymond et al 2010) were carefully considered, and DBS was performed with informed consent at age 18.DBS leads (Medtronic model 3389-40) were inserted under general anesthesia with frame-based MRI-guided stereotaxy and macro-electrode stimulation and into the globus pallidus internus (GPi) and connected to an implantable neural stimulator (Kinetra). Figure 2 shows the location of the contacts used for stimulation.…”

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confidence: 99%

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Deep Brain Stimulation and Dantrolene for Secondary Dystonia in X-Linked Adrenoleukodystrophy

et al. 2014

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Deep brain stimulation (DBS) has been used to treat secondary dystonias caused by inborn errors of metabolism with varying degrees of effectiveness. Here we report for the first time the application of DBS as treatment for secondary dystonia in a 22-year-old male with X-linked adrenoleukodystrophy (X-ALD). The disease manifested at age 6 with ADHD, tics, and dystonic gait, and deteriorated to loss of ambulation by age 11, and speech difficulties, seizures, and characteristic adrenal insufficiency by age 16. DBS in the globus pallidus internus was commenced at age 18. However, after 25 months, no improvement in dystonia was observed (Burke-Fahn-Marsden (BFM) scores of 65.5 and 62 and disability scores of 28 and 26, pre-and post-DBS, respectively) and the DBS device was removed. Treatment with dantrolene reduced skeletal muscle tone and improved movement (Global Dystonia Rating Scores from 5 to 1 and BFM score 42). Therefore, we conclude that DBS was a safe but ineffective intervention in our case with longstanding dystonia, whereas treatment of spasticity with dantrolene did improve the movement disorder in this young man with X-ALD. ReportDeep brain stimulation (DBS) has demonstrated variable effectiveness in secondary dystonias caused by inborn errors of metabolism (e.g., homocystinuria, PKAN, GM1-gangliosidosis) (Andrews et al. 2010;Aydin et al. 2011). The present report of DBS in a now 22-year-old man with a diagnosis of X-linked adrenoleukodystrophy (X-ALD, OMIM# 300100) (Vidailhet et al. 2005) is its first reported application in X-ALD.The patient presented at age 6 with ADHD, tics, and a dystonic gait. Neuroimaging revealed symmetrical occipito-parietal demyelination and abnormal signal intensities in the basal ganglia and thalamus (Fig. 1). Diagnosis was confirmed by elevated very long chain fatty acids in plasma. He lost the ability to ambulate within 5 years, and was wheelchair-bound by age 11. His speech deteriorated and was barely intelligible by age 16. Seizure disorder and adrenal insufficiency were effectively controlled with carbamazepine and clobazam, and hydrocortisone, respectively. Initially the dystonia affected only the lower extremities, but quickly generalized. At age 11 years, mild athetoid movements of the head, neck, and extremities were observed. He held the neck in a flexed position, but was able to extend it on request. He had a tendency to elevate the right upper extremity, with his right wrist in a flexed position and fingers extended. There was mild intermittent flexion of the wrist. Knees were held in an extended position, with ankles plantar flexed and feet inverted (left greater than right). Tone was difficult to assess due to the dystonia. Deep tendon reflexes were brisk, especially at the knees; plantar responses were difficult to assess due to dystonia. Hoffman's sign was absent.For dystonia, botox, levodopa/carbidopamine, trihexyphenidyl, pergolide, and pramipexole were ineffective. Intrathecal baclofen to reduce muscle tone was refused by the patient.Repeat gadoli...

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Section: Reportmentioning

confidence: 99%

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confidence: 99%

Deep Brain Stimulation and Dantrolene for Secondary Dystonia in X-Linked Adrenoleukodystrophy

et al. 2014

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“…Raymond et al (2010) recently reported the impact of moderate to severe head trauma on ALD progression. In their series, Raymond et al (2010) reported three asymptomatic patients and two AMN patients who, after head trauma, developed a CALD phenotype. The posttraumatic neurological progression of both AMN patients was brief and severe.…”

Section: Case Reportmentioning

confidence: 99%

“…The first phase is based on the accumulation of excessive saturated, straight VLCFA in myelin lipids and in PLP1 (Raymond et al 2010). An excess of hexacosanoic acid (C26:0) generates reactive oxygen species altering the physiological properties of myelin and consequently destabilizing the cell membranes.…”

Section: Case Reportmentioning

confidence: 99%

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Onset of Adreno-Leukodystrophy After Medulloblastoma Therapy: Causal Connection or Coincidence?

et al. 2011

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X-linked adreno-leukodystrophy (ALD) is a peroxisomal disorder affecting the white matter of the central nervous system and the adrenal cortex. It is caused by mutations in the ABCD1 gene encoding for a peroxisomal membrane protein. The absent genotype-phenotype correlation implies a contribution by environmental factors to explain the phenotypical heterogeneity. We report on a 4-year-old boy with a biochemically confirmed diagnosis of ALD after birth. At the age of 32 months, the additional diagnosis of a medulloblastoma was made. After treatment of the medulloblastoma, he developed active areas of demyelination representing the characteristic neuroimaging features of ALD. The clinical history of our patient supports the hypothesis that external factors, like neurosurgical intervention as part of medulloblastoma treatment, may accelerate or initiate cerebral ALD-related demyelination. A postsurgical inflammatory reaction may facilitate the inclusion of abnormal fatty acids in myelin. The opening of the blood-brain barrier following neurosurgery may enhance the recognition of previously sequestered antigens considered to play a role in ALD onset. Consequently, neurosurgical disruption of the BBB can precipitate the immune-mediated inflammatory process, which progressively destroys myelin in ALD patients. Tumor-related chemotherapy and/or radiotherapy may also play a contributing role. We suggest that X-ALD patients who undergo neurosurgical intervention need close followup imaging to identify active demyelination early.

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Antioxidant Capacity and Superoxide Dismutase Activity in Adrenoleukodystrophy

et al. 2017

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IMPORTANCE X-linked adrenoleukodystrophy (ALD) may switch phenotype to the fatal cerebral form (ie, cerebral ALD [cALD]), the cause of which is unknown. Determining differences in antioxidant capacity and superoxide dismutase (SOD) levels between phenotypes may allow for the generation of a clinical biomarker for predicting the onset of cALD, as well as initiating a more timely lifesaving therapy.OBJECTIVE To identify variations in the levels of antioxidant capacity and SOD activity between ALD phenotypes in patients with cALD or adrenomyeloneuropathy (AMN), heterozygote female carriers, and healthy controls and, in addition, correlate antioxidant levels with clinical outcome scores to determine a possible predictive value.DESIGN, SETTING, AND PARTICIPANTS Samples of monocytes and blood plasma were prospectively collected from healthy controls, heterozygote female carriers, and patients with AMN or cALD. We are counting each patient as 1 sample in our study. Because adrenoleukodystrophy is an X-linked disease, the affected group populations of cALD and AMN are all male. The heterozygote carriers are all female. The samples were assayed for total antioxidant capacity and SOD activity. The data were collected in an academic hospital setting. Eligibility criteria included patients who received a diagnosis of ALD and heterozygote female carriers, both of which groups were compared with age-matched controls. The prospective samples (n = 30) were collected between January 2015 to January 2016, and existing samples were collected from tissue storage banks at the Kennedy Krieger Institute (n = 30). The analyses were performed during the first 3 months of 2016. MAIN OUTCOME AND MEASURESCommercially available total antioxidant capacity and SOD assays were performed on samples of monocytes and blood plasma and correlated with magnetic resonance imaging severity score.RESULTS A reduction in antioxidant capacity was shown between the healthy controls (0.225 mmol trolox equivalent) and heterozygote carriers (0.181 mmol trolox equivalent), and significant reductions were seen between healthy controls and patients with AMN (0.102 mmol trolox equivalent; P < .01), as well as healthy controls and patients with cALD (0.042 mmol trolox equivalent; P < .01). Superoxide dismutase activity in human blood plasma mirrored these reductions between prospectively collected samples from healthy controls (2.66 units/mg protein) and samples from heterozygote female carriers (1.91 units/mg protein), patients with AMN (1.39 units/mg protein; P = .01), and patients with cALD (0.8 units/mg protein; P < .01). Further analysis of SOD activity in biobank samples showed significant reductions between patients with AMN (0.89 units/mg protein) and patients with cALD (0.18 units/mg protein) (P = .03). Plasma SOD levels from patients with cALD demonstrated an inverse correlation to brain magnetic resonance imaging severity score (R 2 = 0.75, P < .002). Longitudinal plasma SOD samples from the same patients (n = 4) showed decreased activity prior to and at...

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Head trauma can initiate the onset of adreno-leukodystrophy

Cited by 74 publications

References 17 publications

Deep Brain Stimulation and Dantrolene for Secondary Dystonia in X-Linked Adrenoleukodystrophy

Deep Brain Stimulation and Dantrolene for Secondary Dystonia in X-Linked Adrenoleukodystrophy

Onset of Adreno-Leukodystrophy After Medulloblastoma Therapy: Causal Connection or Coincidence?

Antioxidant Capacity and Superoxide Dismutase Activity in Adrenoleukodystrophy

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