Demyelination Of Cerebral White Matter Research Articles

LMNB1‐duplication mediated nuclear architecture alteration and demyelination of cerebral white matter in a patient with ADLD

<i>LMNB1</i>‐duplication mediated nuclear architecture alteration and demyelination of cerebral white matter in a patient with ADLD

Investigation of the relationship between MBP gene polymorphisms and delayed encephalopathy after acute carbon monoxide poisoning

Increasing evidence reveals that delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) results from the combined effects of environmental and genetic factors. The main pathological feature of DEACMP was generalized demyelination of cerebral white matter. Myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) and serum samples from DEACMP patients were elevated. This study investigated the association of MBP single nucleotide polymorphisms(SNPs) (rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336) with DEACMP. We genotyped 416 DEACMP patients and 785 age, educational level, and sex-matched ACMP patients for rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336 SNPs using the Agena MassArray. There were no significant differences in the allele frequency distribution, four genetic models, and genotype distributions between the DEACMP and ACMP groups for rs470555, rs470724, rs4890785, and rs595997. However, significant differences were observed for rs76452994 and rs921336. This study revealed that the MBP polymorphisms, rs470555, rs470724, rs4890785, and rs595997, were not associated with DEACMP. Based on the codominant, dominant, and overdominant genetic inheritability patterns, the MBP rs76452994 and rs921366 polymorphisms were associated with DEACMP. Furthermore, the G allele of rs76452994 and T allele of rs921336 could lead to higher DEACMP risk.

Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.

In vivo tensor-valued diffusion MRI of focal demyelination in white and deep grey matter of rodents

BackgroundMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease leading to damage of white matter (WM) and grey matter (GM). Magnetic resonance imaging (MRI) is the modality of choice to assess brain damage in MS, but there is an unmet need in MRI for achieving higher sensitivity and specificity to MS-related microstructural alterations in WM and GM. ObjectiveTo explore whether tensor-valued diffusion MRI (dMRI) can yield sensitive microstructural read-outs for focal demyelination in cerebral WM and deep GM (DGM). MethodsEight rats underwent L-α-Lysophosphatidylcholine (LPC) injections in the WM and striatum to introduce focal demyelination. Multimodal MRI was performed at 7 Tesla after 7 days. Tensor-valued dMRI was complemented by diffusion tensor imaging, quantitative MRI and proton magnetic resonance spectroscopy (MRS). ResultsQuantitative MRI and MRS confirmed that LPC injections caused inflammatory demyelinating lesions in WM and DGM. Tensor-valued dMRI illustrated a significant decline of microscopic fractional anisotropy (µFA) in both LPC-treated WM and DGM (P < 0.005) along with a marked increase of isotropic kurtosis (MKI) in DGM (P < 0.0001). ConclusionTensor-valued dMRI bears considerable potential for microstructural imaging in MS, suggesting a regional µFA decrease may be a sensitive indicator of MS lesions, while a regional MKI increase may be particularly sensitive in detecting DGM lesions of MS.

Clinical features and genetic mutation analysis in a family of X-linked adrenoleukodystrophy

Objective To analyze the clinical features of a kindred of X-linked adrenoleukodystrophy(X-ALD) with the onset of primary adrenocortical insufficiency, and to detect the mutation of ATP-binding cassette, sub-family D, member l(ABCD1) gene. Methods A Chinese X-ALD kindred with two affected males from two-generations was studied. The clinical data of the proband′s family members were collected. The sequences of ABCD1 of the proband, his parent and young brother were detected by next-generation sequencing. X-ALD was diagnosed according to clinical manifestations, cranial MRI image, and serum level of very long chain fatty acid(VLCFA). Results The two cases were all males. The proband was characteristic of primary adrenocortical insufficiency and neurological dysfunction, with extensive cerebral white matter demyelination and high serum VLCFA level. At the age of 2 years and 10 months, the younger brother of the proband presented with primary adrenocortical dysfunction, without neurological symptoms. Gene sequencing results of two patients showed a novel missense substitution(c.1666C>T) in exon 7 of ABCD1 inherited from their mother. Conclusion The new mutation of ABCDl gene c. 1666C>T may lead to adrenoleukodystrophy. Primary adrenocortical insufficiency and neurological dysfunction are the typical manifestations of X-ALD. Key words: X-linked adrenoleukodystrophy; ABCD1 gene; Mutation detection

Sjogren-Larsson syndrome: Another differential diagnosis of multiple sclerosis in imaging of white matter diseases

Sjogren-Larsson syndrome(SLS) is an inherited autosomal recessive neurocutaneous disorder with congenital ichthyosis, spastic diplegia or quadriplegia and mental retardation. MRI finding such as seen in Multiple sclerosis(MS).So this rare syndrome can be another differential diagnosis of MS. Index patient was 34 year-old female who was admitted because of weakness and inability to walk. She had globaldevelopmental delay.Stiffness in lower limbs started in 4 years before,with progressive increase up to the time of presentation.Physical examination showed generalized dryness of skin most prominent on lower limbs with severe pruritus, that is icthyotic lesion. The nail, plams and soles were affected.She had short stature.In neurological examination she revealed mental retardation,spasticity in both lower limbs;brisk deep tendon reflexes and symmetric bilateral extensor plantar respones.Hoffman sign in upper limbs were detected.She had photophobia. EEG showed mild slowing over both hemispheres.MRI of the brian showed diffuse and no symmetrical plaques with high signal intensity on T2 weighted sequence in bilateral deep periventicular white matter and corpus callosum.Some of these lesion were also plumb to ventricular. The hallmark of SLS is demyelination of cerebral white matter and of the corticospinal and vesibulospinal tracts.MRI reveals abnormal high signal intensity on T2 weight and FLAIR sequences especially in periventicular frontal,parietal lobes,corpus callosum and corona radiata.Typically,subcortical white matter U fibers are spared.

Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study

Demyelination of cerebral white matter is thought to drive neuronal degeneration and permanent neurological disability in individuals with multiple sclerosis. Findings from brain MRI studies, however, support the possibility that demyelination and neuronal degeneration can occur independently. We aimed to establish whether post-mortem brains from patients with multiple sclerosis show pathological evidence of cortical neuronal loss that is independent of cerebral white-matter demyelination. Brains and spinal cords were removed at autopsy from patients, who had died with multiple sclerosis, at the Cleveland Clinic in Cleveland, OH, USA. Visual examination of centimetre-thick slices of cerebral hemispheres was done to identify brains without areas of cerebral white-matter discoloration that were indicative of demyelinated lesions (referred to as myelocortical multiple sclerosis) and brains that had cerebral white-matter discolorations or demyelinated lesions (referred to as typical multiple sclerosis). These individuals with myelocortical multiple sclerosis were matched by age, sex, MRI protocol, multiple sclerosis disease subtype, disease duration, and Expanded Disability Status Scale, with individuals with typical multiple sclerosis. Demyelinated lesion area in tissue sections of cerebral white matter, spinal cord, and cerebral cortex from individuals classed as having myelocortical and typical multiple sclerosis were compared using myelin protein immunocytochemistry. Neuronal densities in cortical layers III, V, and VI from five cortical regions not directly connected to spinal cord (cingulate gyrus and inferior frontal cortex, superior temporal cortex, and superior insular cortex and inferior insular cortex) were also compared between the two groups and with aged-matched post-mortem brains from individuals without evidence of neurological disease. Brains and spinal cords were collected from 100 deceased patients between May, 1998, and November, 2012, and this retrospective study was done between Sept 6, 2011, and Feb 2, 2018. 12 individuals were identified as having myelocortical multiple sclerosis and were compared with 12 individuals identified as having typical multiple sclerosis. Demyelinated lesions were detected in spinal cord and cerebral cortex, but not in cerebral white matter, of people with myelocortical multiple sclerosis. Cortical demyelinated lesion area was similar between myelocortical and typical multiple sclerosis (median 4·45% [IQR 2·54-10·81] in myelocortical vs 9·74% [1·35-19·50] in typical multiple sclerosis; p=0·5512). Spinal cord demyelinated area was significantly greater in typical than in myelocortical multiple sclerosis (median 3·81% [IQR 1·72-7·42] in myelocortical vs 13·81% [6·51-29·01] in typical multiple sclerosis; p=0·0083). Despite the lack of cerebral white-matter demyelination in myelocortical multiple sclerosis, mean cortical neuronal densities were significantly decreased compared with control brains (349·8 neurons per mm2 [SD 51·9] in myelocortical multiple sclerosis vs 419·0 [43·6] in controls in layer III [p=0·0104]; 355·6 [46·5] vs 454·2 [48·3] in layer V [p=0·0006]; 366·6 [50·9] vs 458·3 [48·4] in layer VI [p=0·0049]). By contrast, mean cortical neuronal densities were decreased in typical multiple sclerosis brains compared with those from controls in layer V (392·5 [59·0] vs 454·2 [48·3]; p=0·0182) but not layers III and VI. We propose that myelocortical multiple sclerosis is a subtype of multiple sclerosis that is characterised by demyelination of spinal cord and cerebral cortex but not of cerebral white matter. Cortical neuronal loss is not accompanied by cerebral white-matter demyelination and can be an independent pathological event in myelocortical multiple sclerosis. Compared with control brains, cortical neuronal loss was greater in myelocortical multiple sclerosis cortex than in typical multiple sclerosis cortex. The molecular mechanisms of primary neuronal degeneration and axonal pathology in myelocortical multiple sclerosis should be investigated in future studies. US National Institutes of Health and National Multiple Sclerosis Society.

Anesthesia in a child with adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is rare genetic disorder, and children with ALD are at an increased risk of anesthetic mortality and morbidity [1]. Therefore, they require an individual anesthetic protocol based on their clinical condition. Herein we report the case of a male with childhood-onset X-linked ALD who required general anesthesia for a dental operation. An 11-year-old male (height 143 cm, weight 30 kg) was scheduled for scaling and multiple deciduous tooth extractions under general anesthesia due to his failure to cooperate willingly. He had been diagnosed with childhood-onset X-linked ALD 3 years previously. Other history included an episode of status epilepticus, adrenal insufficiency, aspiration pneumonia, pressure sores and blindness. He was bed-ridden and maintained on a positive-pressure home ventilator via tracheostomy. Physical examination revealed spastic tetraparesis, unresponsiveness to the environment, and cushingoid facies due to chronic steroid supplementation. Preoperative medications including topiramate, divalproex, prednisolone were continued until the morning of the operation. On arrival at the operating room, standard monitoring commenced. For anesthetic induction, 75 mg of pentothal sodium were injected. Anesthesia was maintained using N2O at 2 L/min, O2 at 2 L/min, and sevoflurane. About 5 min after the start of maintenance inhalational anesthesia, the surgeon was unable to open the patient’s mouth so rocuronium 10 mg was injected, after which the mouth could be opened and the surgery commenced. The operation lasted 30 min and was uneventful. Residual neuromuscular blockade was reversed with pyridostigmine 10 mg and glycopyrrolate 0.2 mg, and 15 min after administration of reversal agents, we placed the patient’s home ventilator in pressure-support ventilation (PSV) mode, as it was preoperatively. The patient was observed closely for over 1 h by an anesthesiologist and a pediatrician in the post-anesthesia care unit (PACU). The home ventilator with PSV mode was well tolerated, so we then transferred the patient to the general ward under monitoring with pulse oximetry. X-linked ALD is a progressive neurodegenerative disorder characterized by demyelination of cerebral white matter, axonopathy of the spinal cord, and reduced adrenal response to adrenocorticotropic hormone. The onset age of the condition is between 3 and 10 years, and the patients initially present with behavioral problems and deficits in memory and language. As the disease progresses, vision loss, auditory impairment, hemiparesis and spastic tetraparesis may occur. In the later stages, seizures begin and the patient becomes bedridden, blind, and unable to interact with the environment. Death usually ensues within 2 to 4 years after the onset of symptoms [1]. There are several considerations in anesthetic management for these patients. The anesthetic plan should be formulated based on each individual patient’s condition according to their disease progression. In our case, the anesthetic plan focused on the prevention of seizures and early return to the preoperative condition without any anesthesia-related complications. In an ALD patient with seizure disorders, anticonvulsants should be continued throughout the perioperative period, including the day of surgery, and the anesthesiologist should consider the altered pharmacokinetics of anesthetics due to hepatic microsomal enzyme induction secondary to chronic antiseizure

Fractional anisotropy in the centrum semiovale as a quantitative indicator of cerebral white matter damage in the subacute phase in patients with carbon monoxide poisoning: correlation with the concentration of myelin basic protein in cerebrospinal fluid

Carbon monoxide (CO) poisoning leads to demyelination of cerebral white matter (CWM) fibers, causing chronic neuropsychiatric symptoms. To clarify whether fractional anisotropy (FA) from diffusion tensor imaging in the centrum semiovale can depict demyelination in the CWM during the subacute phase after CO inhalation, we examined correlations between FA in the centrum semiovale and myelin basic protein (MBP) in cerebrospinal fluid. Subjects comprised 26 adult CO-poisoned patients ≤60 years old. MBP concentration was examined for all patients at 2 weeks after CO inhalation. The mean FA of the centrum semiovale bilaterally at 2 weeks was also examined for all patients and 21 age-matched healthy volunteers as controls. After these examinations, the presence of chronic symptoms was checked at 6 weeks after CO poisoning. Seven patients displayed chronic symptoms, of whom six showed abnormal MBP concentrations. The remaining 19 patients presented no chronic symptoms and no abnormal MBP concentrations, with MBP concentrations undetectable in 16 patients. The MBP concentration differed significantly between patients with and without chronic symptoms. The mean FA was significantly lower in patients displaying chronic symptoms than in either patients without chronic symptoms or controls. After excluding the 16 patients with undetectable MBP concentrations, a significant correlation was identified between MBP concentration and FA in ten patients. The present results suggest that FA in the centrum semiovale offers a quantitative indicator of the extent of demyelination in damaged CWM during the subacute phase in CO-poisoned patients.

Clinical characteristics, CT and MRI findings for delayed encephalopathy after acute carbon monoxide poisoning

To investigate clinical and imaging characteristics of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) and their relationship to the prognosis. The clinical, CT and MRI findings in 46 patients with DEACMP were analysed and compared. The main manifestations of the disease were mental and extrapyramidal impairment. CT scan showed diffuse low density changes in bilateral cerebral white matter, bilateral or unilateral globus pallidus or basal ganglia areas. The MRI showed necrosis and degeneration of glodus pallidus and cerebral white matter demyelination mainly around the ventricles, with high signal intensity in T(2)-weighted and equal or low signal intensity in T(1)-weighted as well as the lesions in hippocampus and brain stem. There was the sign of encephalatrophy in the late stage. The positive detectable rate of MRI was 82.1%, higher than that of CT, 43.2%. MRI was more sensitive than CT. The prognosis of the patients is closely related with the age, time of come after DEACMP and the effectiveness of treatment. Both CT and MRI are valuable in the diagnosis and evaluation of the prognosis for DEACMP. MRI is more sensitive than CT in the diagnosis of DEACMP.

Very Long Chain Fatty Acid Analysis of Dried Blood Spots on Filter Paper to Screen for Adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is an X-linked recessive disorder characterized by progressive demyelination of cerebral white matter and adrenal insufficiency. ALD is the most common peroxisomal disease, afflicting 1 in 20 000 male newborns. Patients with childhood ALD manifest changes of character or behavior and a decline of intelligence and visual or motor dysfunction as the first symptoms during school age. Most of them lapse into a vegetative state and die within several years of onset (1). Patients with all clinical subtypes, including childhood ALD, adolescent ALD, adult ALD (cerebral type), adrenomyeloneuropathy, and Addison disease without neurological symptoms, have defects in the ALD gene (2). Defective activity of peroxisomal lignoceroyl-CoA ligase is considered to lead to the accumulation of very long chain fatty acid (VLCFA) in various tissues and fluids as a secondary phenomenon (3)(4). Dietary erucic acid (C22:1) therapy may help prevent neurological deterioration in presymptomatic boys (5)(6). Patients in the early or presymptomatic stages may be candidates for bone marrow transplantation (5)(7). Gene therapy may also become possible. Screening for ALD, especially in the presymptomatic stage, will be important when these therapeutic methods are established, as in the cases of phenylketonuria or maple syrup urine disease. ALD is usually diagnosed by plasma VLCFA analysis (1)(8), sometimes followed by measurement of β-oxidation activity in cultured skin fibroblasts (9) and mutation analysis of the ALD gene (2)(10)(11)(12)(13)(14)(15)(16). However, screening requires a simpler and more economical method to deal with a large number of subjects. Utilization of a dried blood spot on filter paper …

Adrenoleukodystrophy

Purpose: Adrenoleukodystrophy is a hereditary, usually X-linked recessive disorder, characterized by progressive demyelination of cerebral white matter and adrenal insufficiency. Material and Methods and Results: We report the case of a 14-year-old boy, presenting the typical changes in CT and MR with almost symmetrical changes in the white matter only, with no mass effect and a rim of enhancement. Adrenoleukodystrophy may resemble tumour but shows no mass effect. Discussion and Conclusion: We discuss the differential diagnoses and underline the importance of the characteristic appearance of this disease. Adrenoleukodystrophy is diagnosed by serum analysis.

Adrenoleukodystrophy

Adrenoleukodystrophy is a hereditary, usually X-linked recessive disorder, characterized by progressive demyelination of cerebral white matter and adrenal insufficiency. We report the case of a 14-year-old boy, presenting the typical changes in CT and MR with almost symmetrical changes in the white matter only, with no mass effect and a rim of enhancement. Adrenoleukodystrophy may resemble tumour but shows no mass effect. We discuss the differential diagnoses and underline the importance of the characteristic appearance of this disease. Adrenoleukodystrophy is diagnosed by serum analysis.

Cerebral Demyelination with 5-Fluorouracil and Levamisole

We report a patient who developed multifocal cerebral demyelination with the use of 5-fluorouracil, levamisole, and leucovorin as adjuvant treatment for intestinal adenocarcinoma. The clinical features were acute confusion, restlessness, ataxia, and slurred speech. Magnetic resonance imaging revealed multifocal enhancing white matter lesions. Brain biopsy showed a well-demarcated area of demyelination in cerebral white matter. The patient improved clinically and radiologically after cessation of chemotherapy and a short course of steroids. There have been only 4 previously reported cases of multifocal leukoencephalopathy related to the use of combination 5-fluorouracil and levamisole. The extensive use of these agents as adjuvant treatment for colorectal carcinoma may result in more frequent recognition of this form of neurological toxicity.

MR imaging appearance of childhood adrenoleukodystrophy with auditory, visual, and motor pathway involvement.

Childhood adrenoleukodystrophy is an X chromosome-linked disorder characterized by progressive demyelination of cerebral white matter and adrenal insufficiency. Magnetic resonance (MR) imaging was performed in 15 patients with symptomatic disease and three with presymptomatic disease. MR imaging findings were abnormal only in symptomatic patients. Major sites of disease were the occipital, parietal, and temporal lobes, with all patients showing involvement of occipital lobes, optic radiations, and splenium of the corpus callosum. Follow-up images obtained in four patients demonstrated a posterior-to-anterior progression of disease. Correlation of results from MR imaging with those from evoked potential studies indicated that MR imaging was the method of choice for detecting demyelination of visual, auditory, and motor systems in adrenoleukodystrophy.