Nitrous oxide-induced demyelination: Clinical presentation, diagnosis and treatment recommendations.

BACKGROUND: Recreational use of nitrous oxide (NO) in the general public has led to increasing reports of NO-induced demyelination (NOID). We describe the varying clinical presentations and pathophysiology, and offer a treatment paradigm. METHODS: A literature search of MEDLINE and EMBASE resulted in 42 publications with 37 studies meeting the inclusion criteria, for a total of 51 patients. Our case series included 5 patients seen from 2014 to 2018 followed over 3-60 months. RESULTS: Those with sensory symptoms and subjective weakness were categorized as having "mild" symptoms (25%). Symptoms indicating involvement outside the dorsal columns such as observer-graded weakness were categorized as "moderate" (61%). Patients with the aforementioned plus cognitive effects were categorized as "severe" (12%). There was no dose-dependent relationship between the amount of NO used and clinical impairment. There was a trend between the severity of neurologic impairment and serum levels of B12. Two patients were noncompliant. One initiated only oral therapy and did not improve. One received injections a month apart and worsened. CONCLUSIONS: Patients with NOID tend to have worse symptoms when presenting with lower serum vitamin B12 levels and have good recovery rates when treated with intramuscular B12 and oral supplementation.

Eye movements in demyelinating, autoimmune and metabolic disorders.

PURPOSE OF REVIEW: In the last three decades, the use of eye movements and vestibular testing in many neurological disorders has accelerated, primarily because of practical technologic developments. Although the acute vestibular syndrome is a prime example of this progress, more chronic neurologic and systemic disorders have received less attention. We focus here on recent contributions relating vestibular and ocular motor abnormalities in inflammatory, demyelinating, metabolic, and peripheral nervous system disorders RECENT FINDINGS: Vestibular abnormalities have been identified in acute demyelinating neuropathies (AIDP), in novel genetic mutations responsible for CANVAS (cerebellar ataxia, neuropathy vestibular areflexia syndrome), and in other inherited neuropathies (variants of Charcot-Marie-Tooth disease). In addition, there are differentiating characteristics between the most common CNS demyelinating disorders: multiple sclerosis and neuromyelitis optica (NMO). We summarize new information on Vitamin D metabolism in benign paroxysmal positional vertigo (BPPV), followed by a brief review of the vestibular and ocular motor findings in Wernicke's encephalopathy. We conclude with findings in several paraneoplastic/autoimmune disorders. SUMMARY: This literature review highlights the impact of a careful vestibular and ocular motor evaluation in common neurologic disorder, not only for the initial diagnosis but also for monitoring disease and rehabilitation. A careful examination of eye movements and vestibular function, supplemented with new video techniques to quantify the findings, should be part of the standard neurologic examination.

Cognitive impairment in Chinese IIDDs revealed by MoCA and P300.

To investigate the value of MoCA and auditory P300 as a cognitive assessment tool in chinese idiopathic inflammatory-demyelinating diseases (IIDDs), eighty three consecutive patients with IIDDs and thirteen sex- and age-matched healthy controls were recruited in the study. MMSE, MoCA and auditory P300 potential were administrated to each participant. The percentage of cognitive impairment in IIDDs patients was 24.1% by using MMSE, while the percentage was 81.9% by using MoCA. The majority of IIDDs participants had MMSE scores in the normal range. In contrast, few IIDDs participants scored in the normal range on the MoCA. Age, EDSS and depression correlated negatively with the total score of MoCA and MMSE. Years of education correlated positively with MoCA and MMSE. ADEM patients scored lower on all MoCA subtests. Prolonged latency P300 which negatively correlated with MoCA and reduced P300 amplitude which positively correlated with MoCA were detected in IIDDs patients. Thus MoCA is superior to the MMSE as a cognitive impairment scan tool and P300 is useful for detecting cogntive deficiency in chinese IIDDs.

Higher intake of omega-3 polyunsaturated fatty acids is associated with a decreased risk of a first clinical diagnosis of central nervous system demyelination: Results from the Ausimmune Study.

BACKGROUND: There is contradictory evidence for a role of dietary fat in risk of multiple sclerosis (MS). OBJECTIVES: To examine the association between usual fat intake (total, saturated, monounsaturated (MUFA), polyunsaturated (PUFA), omega-3 and omega-6) and risk of a first clinical diagnosis of CNS demyelination (FCD). METHODS: Multi-centre incident case-control study in four regions of Australia during 2003-2006. Cases were aged 18-59 years and had a FCD; controls were matched to a case on age, sex and location. Dietary data were collected using a validated food frequency questionnaire. RESULTS: In 267 cases and 517 controls with dietary data, higher intake (per g/day) of omega-3 PUFA (adjusted odds ratio, AOR=0.61 (95% CI 0.40-0.93)), and particularly that derived from fish (AOR=0.54 (95% CI 0.31-0.93)) rather than from plants (AOR=0.75 (95% CI 0.39-1.43)) was associated with a decreased risk of FCD. Total fat intake and intake of other types of fat were not associated with FCD risk. CONCLUSIONS: There was a significant decrease in FCD risk with higher intake of omega-3 PUFA, particularly that originating from fish. There was no evidence to indicate that the intake of other types of dietary fat or fat quantity in the previous 12 months was associated with an altered risk of FCD.

[Intracerebral xanthogranuloma with specific MRI features: a case report].

We report a case of a 47-year-old male who had a left frontal lobe mass with specific magnetic resonance imaging (MRI). Four years previous to his admission to our hospital, he developed acute myelocytic leukemia and he was implanted with peripheral blood stem cell transplantation. One month before his admission, he was unable to walk due to right leg motor weakness. MRI revealed a round mass lesion at the left frontal lobe. Initial diagnosis was a brain abscess, so he was administered some antibacterial drug. However, his neurological symptoms kept getting worse with increase of mass size on MRI. T1-weighted MR images showed the mass as a low intensity lesion with incomplete ring-like Gd-enhancement. T2-weighted images showed the mass as a high intensity lesion with many linear shadows inside the mass. Diffusion weighted images showed the mass as a low intensity lesion. MR spectroscopy revealed an elevation of choline and lactate peak. Differential diagnosis was glioma or demyelinating disease. At the operation, the mass was light yellow and seen to be rich with vessels. The pathological diagnosis was xanthogranuloma in the brain. Postoperative course was uneventful. The frontal residual mass lesion decreased in size and Gd-enhancement.

1H-magnetic resonance spectroscopy indicates damage to cerebral white matter in the subacute phase after CO poisoning.

OBJECTIVE: The authors examined whether (1)H-magnetic resonance spectroscopy (MRS) can identify damage to the centrum semiovale in the subacute phase after CO exposure. METHODS: Subjects comprised 29 adult patients who were treated with hyperbaric oxygenation within a range of 4-95 h (mean 18.7 h) after CO exposure. Subjects were classified into three groups according to clinical behaviours: Group A, patients with transit acute symptoms only; Group P, patients with persistent neurological symptoms; and Group D, patients with 'delayed neuropsychiatric sequelae' occurring after a lucid interval. MRS of bilateral centrum semiovale was performed 2 weeks after CO inhalation for all patients and 13 healthy volunteers. The mean ratios of choline-containing compounds/creatine ((mean)Cho/Cr) and N-acetylaspartate/Cr ((mean)NAA/Cr) for bilateral centrum semiovale were calculated and compared between the three CO groups and controls. Myelin basic protein (MBP) concentration in cerebrospinal fluid was examined at 2 weeks to evaluate the degree of demyelination in patients. RESULTS: MBP concentration was abnormal for almost all patients in Groups P and D, but was not abnormal for any Group A patients. The (mean)Cho/Cr ratios were significantly higher in Groups P and D than in Group A. No significant difference in (mean)NAA/Cr ratio was seen between the three pathological groups and controls. A significant correlation was identified between MBP and (mean)Cho/Cr ratio. CONCLUSIONS: These results suggest that the Cho/Cr ratio in the subacute phase after CO intoxication represents early demyelination in the centrum semiovale, and can predict chronic neurological symptoms.

[Rapid improvement of callosal edema by thiamine administration in Marchiafava-Bignami disease: a case report].

Marchiafava-Bignami disease (MBD) associated with chronic alcoholism is a fatal disorder characterized by demyelination of the corpus callosum. A 62-year-old Japanese man, a heavy drinker for his last over 10 years, was admitted to our hospital because of acute onset of speech disturbance. The first MR images showed abnormal signal intensity of the corpus callosum, which was a typical finding of MBD, but no signal abnormality on diffusion-weighted images. At three days after large doses of thiamine administration, MR studies revealed the disappearance of callosal high signal intensity. His symptom gradually improved, the pathogenesis and therapy of MBD were discussed.

The Danish PET/depression project: performance on Stroop's test linked to white matter lesions in the brain.

The Stroop test (ST) assesses the integrity of prefrontal and cingulate functioning. Patients with major depression perform poorly on the ST, pointing to disturbed function in these areas. We therefore used positron emission tomography to study 41 in-patients with major depression and 46 age- and gender-matched controls during neuropsychological activation with the ST. Magnetic resonance imaging was used for coregistration and for description of the localization of white matter lesions (WML). The cerebral blood flow (CBF) changes during ST were mapped for each of the two study groups, and inter-group differences were calculated on a voxel-by-voxel basis. The patients were followed for 3 to 5 years to ensure diagnostic stability. The control group activated anterior cingulate regions, prefrontal cortices, insula, thalamus and cerebellum. Despite the patients' slower performance with more errors, no significant differences were found comparing the activations in the two groups. The performance was, however, correlated to the number of WML in frontal lobes, insula and adjacent to the basal ganglia, whereas WML in other locations was not related to performance. We thus partly explain the poorer performance by increased frequency of WML in frontostriatal pathways in the depressed patients, impairing neurotransmission.

White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy.

PURPOSE: The purpose of this study was to determine the time course for development of white matter changes induced by high-dose chemotherapy. METHODS: Eight patients with advanced breast cancer were entered into a prospective, longitudinal trial that included examination by MR imaging and proton MR spectroscopy before chemotherapy and through 12 months after treatment with carmustine, cyclophosphamide, and cisplatin, combined with autologous hematopoietic progenitor cell support (AHPCS). RESULTS: Six patients completed induction chemotherapy, at which time all MR imaging studies appeared normal. At 3 months after the conclusion of high-dose chemotherapy and beyond, three of the four patients remaining in the study showed an increasing volume of white matter changes, which appeared to stabilize during the period from 6 months to 1 year. Maximal volumes of abnormal white matter ranged from 73 to 166 cm3. MR spectroscopy showed little or no change in metabolic ratios through the period of observation, although there was a suggestion of small transient treatment-related decreases in the ratio of N-acetyl aspartate (NAA) to creatine. CONCLUSION: White matter changes are common sequelae of treatment with high-dose chemotherapy combined with AHPCS, occurring early in the period following high-dose chemotherapy, with a rapid and progressive accumulation to about 6 months, but not accompanied by persistent neurologic symptoms. The MR spectroscopic analyses suggest a minimal disturbance of the neuronal marker NAA, a finding that may in part explain the good neurologic outcome.

Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings.

Vitamin B12 deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Lack of vitamin B12 in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. We report the case of a 14(1)/2-month-old child of strictly vegetarian parents who presented with severe psychomotor retardation. This severely hypotonic child had anemia due to insufficient maternal intake of vitamin B12 with associated megaloblastic anemia. MRI of the brain revealed severe brain atrophy with signs of retarded myelination, the frontal and temporal lobes being most severely affected. It was concluded that this myelination retardation was due to insufficient intake of vitamin B12 and vitamin B12 therapy was instituted. The patient responded well with improvement of clinical and imaging abnormalities. We stress the importance of MRI in the diagnosis and follow-up of patients with suspected diseases of myelination.

Ocular toxicity following high dose chemotherapy and autologous transplant.

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Carmofur-induced leukoencephalopathy: MRI.

Carmofur, a derivative of 5-fluorouracil, has recently been noted to have an infrequent but serious association with leukoencephalopathy. To our knowledge, there has been no report of early MRI findings in this leukoencephalopathy. We describe a case in which diffuse high signal intensity of the entire cerebral white matter, including the corpus callosum, was seen on T2-weighted magnetic resonance images. Although similar findings can be seen in many other diseases, carmofur-induced leukoencephalopathy should be suspected in a patient treated with carmofur. It is important to know the clinical and MRI characteristics of this condition, for early diagnosis and better prognosis.

Multifocal inflammatory leukoencephalopathy developing in a patient receiving 5-fluorouracil and levamisole.

A single case of multifocal inflammatory leukoencephalopathy, which developed during a course of adjuvant chemotherapy with 5-fluorouracil (5FU) and levamisole is reported. Clinical features developed slowly and were not dramatic; this condition may therefore frequently be missed.