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.

Impacto de la pandemia COVID-19 en pacientes con enfermedades desmielinizantes / IMPACT OF THE COVID-19 PANDEMIC ON PATIENTS WITH DEMYELINIZING DISEASES

Introducción: A más de un año del inicio de la pandemia, el seguimiento y la atención presencial de pacientes con enfermedades desmielinizantes se ha visto modificado. Según la evidencia, pacientes con diagnóstico de esclerosis múltiple (EM), síndrome desmielinizante aislado (SDA), Síndrome Radiológico Aislado (SRA) o enfermedades del espectro de neuromielitis óptica (NMO) no parecen ser un grupo de riesgo para COVID19 por el hecho de tener la enfermedad. La presencia de ciertas condiciones puede hacerlos susceptibles de cursar infección severa. Se ha descripto una asociación de curso grave con drogas anti CD20, faltan datos sobre la respuesta a vacunas COVID19 en esta población. Objetivos: Establecer características clínico-epidemiológicas de pacientes con enfermedades desmielinizantes que han padecido COVID-19 y describir su evolución. Caracterizar población vacunada, evaluar acceso al seguimiento médico/ terapéutico durante la pandemia. Materiales y métodos: Estudio observacional descriptivo. Se revisaron las historias clínicas de 168 pacientes con EM, SDA y SRA y 33 pacientes con NMO correspondientes al Hospital de Clínicas José de San Martin. Mediante encuesta telefónica se evaluó adherencia al tratamiento, evolución clínica, infección COVID-19, vacunación y acceso durante la pandemia. Resultados: Se encontraron 49 pacientes que desarrollaron COVID-19 en el grupo de pacientes con EM, y 7 en el grupo de NMO. Del primer grupo ninguno requirió internación, mientras que en el segundo, 2 fueron hospitalizados y uno de ellos falleció. La complicación post-COVID más frecuente fue: astenia prolongada y 3 pacientes presentaron un brote de la enfermedad de base en los 3 meses posteriores. Cerca del 90% de nuestra población ya contaba con al menos 1 dosis de vacuna para SARS-CoV2. Se interrogó sobre el acceso a la consulta neurológica y casi el 70% de los pacientes otorgó máximo puntaje al acceso a consultas virtuales. Conclusión: Los pacientes con enfermedades desmielinizantes que cursaron COVID-19 no tuvieron complicaciones severas por la infección, con solamente 2 pacientes cursando un brote en los 3 meses posteriores. No observamos reacciones adversas severas post vaccinales, ni infección posterior, sólo 2 pacientes presentaron un brote en el período post aplicación. Gran cantidad de pacientes percibieron acceso fluido a sus neurólogos de manera virtual, lo que podría relacionarse con alta tasa de adherencia a sus tratamientos a pesar de la limitación a la consulta presencial.

Introduction: More than a year after the start of the pandemic, the follow-up and face-to-face care of patients with demyelinating diseases has been modified. According to the evidence, patients with a diagnosis of multiple sclerosis (MS), isolated demyelinating syndrome (ADS), Isolated Radiological Syndrome (RAS) or neuromyelitis optica (NMO) spectrum diseases do not seem to be a risk group for COVID19 due to the fact that they have the disease. The presence of certain conditions can make them susceptible to severe infection. A severe course association with anti-CD20 drugs has been described, data on the response to COVID19 vaccines in this population are lacking. Objectives: To establish clinical-epidemiological characteristics of patients with demyelinating diseases who have suffered from COVID-19 and describe their evolution. Characterize the vaccinated population, evaluate access to medical/therapeutic follow-up during the pandemic. Materials and methods: Descriptive observational study. The medical records of 168 patients with MS, ADS and ARS and 33 patients with NMO corresponding to the Hospital de Clínicas José de San Martin were reviewed. Through a telephone survey, adherence to treatment, clinical evolution, COVID-19 infection, vaccination, and access during the pandemic were evaluated. Results: 49 patients who developed COVID-19 were found in the MS patient group, and 7 in the NMO group. Of the first group, none required hospitalization, unlike in the second, 2 were hospitalized and one of them died. The most frequent post-COVID complication was: prolonged asthenia and 3 patients presented an outbreak of the underlying disease in the following 3 months. Close to 90% of our population already had at least 1 dose of SARS-CoV2 vaccine. Access to the neurological consultation was questioned and almost 70% of the patients gave the highest score to access to virtual consultations. Conclusion: Patients with demyelinating diseases who had COVID-19 did not have severe complications from the infection, with only 2 patients having an outbreak in the subsequent 3 months. We did not observe severe post-vaccinal adverse reactions, nor subsequent infection, only 2 patients presented an outbreak in the post-application period. A large number of patients perceived fluid access to their neurologists virtually, which could be related to a high rate of adherence to their treatments despite the limitation to face-to-face consultation

Brain stem and spinal cord demyelination due to acute carbon monoxide poisoning.

Demyelination throughout the brain stem and spinal cord caused by acute carbon monoxide (CO) poisoning has not been previously reported. Magnetic resonance imaging (MRI) has revealed that acute CO poisoning primarily affects the subcortical white matter of the bilateral cerebral hemispheres and basal ganglia. Here we report the case of a patient with delayed neuropsychological sequelae (DNS) due to acute CO poisoning. A 28-year-old man was admitted to our department following a suicide attempt by acute CO poisoning. After a six-month pseudo-recovery period, he was diagnosed with DNS, with MRI evidence of demyelinating change of the bilateral cerebral peduncles. Demyelination was identified throughout the brain stem, expanding from the bilateral cerebral peduncles to the medulla oblongata, occurring approximately six months after poisoning. One and a half years after acute CO poisoning, demyelination of the cervical and thoracic spine was observed, most notable in the lateral and posterior cords. It is evident that previously published research on this topic is extremely limited. Perhaps in severe cases of acute CO poisoning the fatality rate is higher, leading to fewer surviving cases for possible study. This may be because a more severe case of acute CO poisoning would result in the higher likelihood of secondary demyelination. This research indicates that clinicians should be aware of the risk of secondary demyelination and take increased precautions such as vitamin B supplementation and administration of low-dose corticosteroids for an extended period of time in order to reduce the extent and severity of demyelination.

Electroacupuncture Alleviates Diabetic Peripheral Neuropathy by Regulating Glycolipid-Related GLO/AGEs/RAGE Axis.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM) and affects over one-third of all patients. Neuropathic pain and nerve dysfunction induced by DM is related to the increase of advanced glycation end products (AGEs) produced by reactive dicarbonyl compounds in a hyperglycemia environment. AGEs induce the expression of pro-inflammatory cytokines via the main receptor (RAGE), which has been documented to play a crucial role in the pathogenesis of diabetic peripheral neuropathy. Electroacupuncture (EA) has been reported to have a positive effect on paralgesia caused by various diseases, but the mechanism is unclear. In this study, we used high-fat-fed low-dose streptozotocin-induced rats as a model of type 2 diabetes (T2DM). Persistent metabolic disorder led to mechanical and thermal hyperalgesia, as well as intraepidermal nerve fiber density reduction and nerve demyelination. EA improved neurological hyperalgesia, decreased the pro-inflammatory cytokines, reduced the generation of AGEs and RAGE, and regulated the glyoxalase system in the EA group. Taken together, our study suggested that EA plays a role in the treatment of T2DM-induced DPN, and is probably related to the regulation of metabolism and the secondary influence on the GLO/AGE/RAGE axis.

Short-term changes in frequencies of circulating leukocytes associated with narrowband UVB phototherapy in people with clinically isolated syndrome.

Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). Low environmental exposure to UV radiation is implicated in risk of developing MS, and therefore, narrowband UVB phototherapy might delay progression to MS in people with CIS. Twenty individuals with CIS were recruited, and half were randomised to receive 24 sessions of narrowband UVB phototherapy over a period of 8 weeks. Here, the effects of narrowband UVB phototherapy on the frequencies of circulating immune cells and immunoglobulin levels after phototherapy are reported. Peripheral blood samples for all participants were collected at baseline, and 1, 2, 3, 6 and 12 months after enrolment. An extensive panel of leukocyte populations, including subsets of T cells, B cells, monocytes, dendritic cells, and natural killer cells were examined in phototherapy-treated and control participants, and immunoglobulin levels measured in serum. There were significant short-term increases in the frequency of naïve B cells, intermediate monocytes, and fraction III FoxP3+ T regulatory cells, and decreases in switched memory B cells and classical monocytes in phototherapy-treated individuals. Since B cells are increasingly targeted by MS therapies, the effects of narrowband UVB phototherapy in people with MS should be investigated further.

Low-level laser therapy modulates demyelination in mice.

There are no effective therapies for remyelination. Low-level laser therapy (LLLT) has been found advantageous in neurogenesis promotion, cell death prevention, and modulation of inflammation in central and peripheral nervous system models. The purpose of this study was to analyse LLLT effects on cuprizone-induced demyelination. Mice were randomly distributed into three groups: Control Laser (CTL), Cuprizone (CPZ), and Cuprizone Laser (CPZL). Mice from CPZ and CPZL groups were exposed to a 0.2% cuprizone oral diet for four complete weeks. Six sessions of transcranial laser irradiation were applied on three consecutive days, during the third and fourth weeks, with parameters of 36 J/cm2, 50 mW, 0.028 cm2 spot area, continuous wave, 1 J, 20 s, 1.78 W/cm2 in a single point equidistant between the eyes and ears of CTL and CPZL mice. Motor coordination was assessed by the rotarod test. Twenty-four hours after the last laser session, all animals were euthanized, and brains were extracted. Serum was obtained for lactate dehydrogenase toxicity testing. Histomorphological analyses consisted of Luxol Fast Blue staining and immunohistochemistry. The results showed that laser-treated animals presented motor performance improvement, attenuation of demyelination, increased number of oligodendrocyte precursor cells, modulated microglial and astrocytes activation, and a milder toxicity by cuprizone. Although further studies are required, it is suggested that LLLT represents a feasible therapy for demyelinating diseases.

Combined therapy involving electroacupuncture and treadmill exercise attenuates demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat model of neonatal hypoxia-ischemia.

We investigated whether electroacupuncture (EA) and treadmill (TM) exercise improve behaviors related to motor and memory dysfunction in a cerebral palsy-like rat model via activation of oligodendrogenesis. A neonatal hypoxia-ischemia model was created using Sprague-Dawley rats (P7), and these underwent EA stimulation and treadmill training from 3 to 5weeks after hypoxia-ischemia induction. EA treatment was delivered via electrical stimulation (2Hz, 1mA) at two acupoints, Baihui (GV20) and Zusanli (ST36). Behavioral tests showed that EA alleviated motor dysfunction caused by hypoxia-ischemia on a rotarod test, and TM exercise alleviated motor and memory dysfunction seen on cylinder and passive avoidance tests. Combined therapy with EA and TM exercise showed synergistic effects on the cylinder, rotarod, and catwalk tests. TM exercise significantly restored corpus callosum thickness, and combined therapy with EA and TM restored myelin basic protein (MBP) levels in this region. While EA stimulation only increased activation of cAMP-response element binging protein (CREB) in oligodendrocytes of the corpus callosum, TM exercise increased newly generated oligodendrocyte progenitor cells or oligodendrocytes via activation of CREB. Synergistic effects on oligodendrogenesis were also observed by the combined therapy. Furthermore, the combined therapy induced mature brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex. These results demonstrate that combined therapy with EA and TM exercise may restore myelin components following neonatal hypoxia-ischemia via upregulation of oligodendrogenesis involving CREB/BDNF signaling, which subsequently improves motor and memory function. Therefore, combined therapy with EA and TM exercise offers another treatment option for functional recovery from injuries caused by neonatal hypoxia-ischemia, such as cerebral palsy.

Neuregulin-1 promotes remyelination and fosters a pro-regenerative inflammatory response in focal demyelinating lesions of the spinal cord.

Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination. We delivered recombinant human Nrg-1ß1 (rhNrg-1ß1) intraspinally in the vicinity of LPC demyelinating lesion in a sustained manner using poly lactic-co-glycolic acid microcarriers. Availability of Nrg-1 promoted generation and maturation of new oligodendrocytes, and accelerated endogenous remyelination by both oligodendrocyte and Schwann cell populations in demyelinating foci. Importantly, Nrg-1 enhanced myelin thickness in newly remyelinated spinal cord axons. Our complementary in vitro studies also provided direct evidence that Nrg-1 significantly promotes maturation of new oligodendrocytes and facilitates their transition to a myelinating phenotype. Nrg-1 therapy remarkably attenuated the upregulated expression chondroitin sulfate proteoglycans (CSPGs) specific glycosaminoglycans in the extracellular matrix of demyelinating foci and promoted interleukin-10 (IL-10) production by immune cells. CSPGs and IL-10 are known to negatively and positively regulate remyelination, respectively. We found that Nrg-1 effects are mediated through ErbB2 and ErbB4 receptor activation. Our work provides novel evidence that dysregulated levels of Nrg-1 in demyelinating lesions of the spinal cord pose a challenge to endogenous remyelination, and appear to be an underlying cause of myelin thinning in newly remyelinated axons.

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats.

OBJECTIVES: In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether 'Governor Vessel' (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. METHODS: Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. RESULTS: EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. CONCLUSIONS: The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination.

Low-level laser therapy ameliorates disease progression in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating inflammatory disease characterized by recurrent episodes of T cell-mediated immune attack on central nervous system (CNS) myelin, leading to axon damage and progressive disability. The existing therapies for MS are only partially effective and are associated with undesirable side effects. Low-level laser therapy (LLLT) has been clinically used to treat inflammation, and to induce tissue healing and repair processes. However, there are no reports about the effects and mechanisms of LLLT in experimental autoimmune encephalomyelitis (EAE), an established model of MS. Here, we report the effects and underlying mechanisms of action of LLLT (AlGaInP, 660 nm and GaAs, 904 nm) irradiated on the spinal cord during EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG35-55 peptide emulsified in complete Freund's adjuvant. Our results showed that LLLT consistently reduced the clinical score of EAE and delayed the disease onset, and also prevented weight loss induced by immunization. Furthermore, these beneficial effects of LLLT seem to be associated with the down-regulation of NO levels in the CNS, although the treatment with LLLT failed to inhibit lipid peroxidation and restore antioxidant defense during EAE. Finally, histological analysis showed that LLLT blocked neuroinflammation through a reduction of inflammatory cells in the CNS, especially lymphocytes, as well as preventing demyelination in the spinal cord after EAE induction. Together, our results suggest the use of LLLT as a therapeutic application during autoimmune neuroinflammatory responses, such as MS.

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.

Remyelination after Lysophosphatidyl Choline-Induced Demyelination Is Stimulated by Bone Marrow Stromal Cell-Derived Oligoprogenitor Cell Transplantation.

Bone marrow stromal cells (BMSCs) are a desirable cell source that may be useful for the treatment of neurodegenerative diseases given their capacity to differentiate into various types of cells. The current study aimed to investigate whether oligoprogenitor cell (OPC)-derived BMSCs have therapeutic benefits in an animal model of local demyelination. BMSCs were transdifferentiated into OPCs using a defined culture medium supplemented with a combination of inducers. The differentiation capacity of the BMSCs was evaluated at the end of the induction phase by assessing the expression levels of the glial-specific markers oligodendrocyte transcription factor 2 and O4 surface antigen. Local demyelination was induced in the corpus callosum of adult female rats via direct injection of lysophosphatidylcholine (LPC) followed by engraftment of BMSC-generated OPCs. The rats were divided into sham control, vehicle control, and cell-transplanted groups. The changes in the extent of demyelination and the robustness of the remyelination event were assessed using Luxol Fast Blue staining and immunohistochemical analysis 1 week after LPC injection and 2 weeks after cell transplantation. Consequently, transplantation of OPCs into the demyelinated corpus callosum model resulted in differentiation of the cells into mature oligodendrocytes that were immunopositive for myelin basic protein. Furthermore, OPC transplantation mitigated demyelination and augmented remyelination relative to controls. These findings suggest that BMSC-derived OPCs can be utilized in therapeutic approaches for the management of demyelination-associated diseases such as multiple sclerosis.

Combination of electroacupuncture and grafted mesenchymal stem cells overexpressing TrkC improves remyelination and function in demyelinated spinal cord of rats.

This study attempted to graft neurotrophin-3 (NT-3) receptor (TrkC) gene modified mesenchymal stem cells (TrkC-MSCs) into the demyelinated spinal cord and to investigate whether electroacupuncture (EA) treatment could promote NT-3 secretion in the demyelinated spinal cord as well as further enhance grafted TrkC-MSCs to differentiate into oligodendrocytes, remyelination and functional recovery. Ethidium bromide (EB) was microinjected into the spinal cord of rats at T10 to establish a demyelinated model. Six groups of animals were prepared for the experiment: the sham, PBS, MSCs, MSCs+EA, TrkC-MSCs and TrkC-MSCs+EA groups. The results showed that TrkC-MSCs graft combined with EA treatment (TrkC-MSCs+EA group) significantly increased the number of OPCs and oligodendrocyte-like cells differentiated from MSCs. Immunoelectron microscopy showed that the oligodendrocyte-like cells differentiated from TrkC-MSCs formed myelin sheaths. Immunofluorescence histochemistry and Western blot analysis indicated that TrkC-MSCs+EA treatment could promote the myelin basic protein (MBP) expression and Kv1.2 arrangement trending towards the normal level. Furthermore, behavioural test and cortical motor evoked potentials detection demonstrated a significant functional recovery in the TrkC-MSCs+EA group. In conclusion, our results suggest that EA treatment can increase NT-3 expression, promote oligodendrocyte-like cell differentiation from TrkC-MSCs, remyelination and functional improvement of demyelinated spinal cord.

Biotherapies in multiple sclerosis: a step toward remyelination and neuroprotection?

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS), characterized by CNS-restricted inflammation with subsequent demyelination and neurodegeneration. Current disease-modifying therapies efficiently reduce relapse rate and new lesions appearance, but still fail to impact the progressive course of the disease. There is a great need for the avenue of new therapies aimed at promoting myelin repair or reducing neurodegeneration that should result in the prevention of neurological disability in this chronic disease. This review will focus on the potentials and limitations of biotherapies that are currently developed for the promotion of CNS repair in MS, either monoclonal antibodies targeting axonal growth and remyelination, or cell therapies aimed at replacing the depleted myelinating cells within the CNS. As other researches aimed at promoting neuroprotection or remyelination are following a classical pharmacological approach, they will not be described in this review, which will focus on antibody-based therapies and cell therapies.

An experimental electro-acupuncture study in treatment of the rat demyelinated spinal cord injury induced by ethidium bromide.

Oligodendrocyte precursor cells (OPCs) are one of the potential treating tools for multiple sclerosis (MS). Therefore, the cell number and differentiation of OPCs in a demyelinated spinal cord are crucial for improvement of reparative process. In the present study, we investigated whether "Governor Vessel (GV)" electro-acupuncture (EA) could efficiently promote increase in cell number and differentiation of OPCs into oligodendrocytes, remyelination and functional recovery in the demyelinated spinal cord. The spinal cord of adult Sprague-Dawley rats was microinjected with ethidium bromide (EB) at T10, to establish a demyelinated model. Six groups of animals were performed for the experiment. After 15 days EA treatment, neurotrophin-3 (NT-3) level and number of NG2-positive OPCs were significantly increased. Compared with the sham group, more NG2-positive OPCs were distributed between neurofilament (NF)-positive nerve fibres or closely associated with them in the lesion site and nearby tissue. In rats given longer EA treatment for 30 days, the number of adenomatous polyposis coli (APC)-positive oligodendrocytes was increased. Concomitantly, the number of newly formed myelins was increased. This was coupled by increase in endogenous oligodendrocyte involved in myelin formation. Furthermore, behavioural test and spinal cord evoked potential detection demonstrated a significant functional recovery in the EA+EB day 30 group. Our results suggest EA treatment can promote NT-3 expression, increase the cell number and differentiation of endogenous OPCs, and remyelination in the demyelinated spinal cord as well as the functional improvement of demyelinated spinal cord.

Transcranial magnetic stimulation shows impaired transcallosal inhibition in Marchiafava-Bignami syndrome.

A case of Marchiafava-Bignami (MB) syndrome with selective callosal involvement was evaluated by clinical examination and magnetic resonance imaging (MRI) in the acute phase and 6 months after the onset of symptoms; at the same time, the corticospinally and transcallosally mediated effects elicited by transcranial magnetic stimulation (TMS) were investigated. The first MRI study showed the presence of extensive abnormal signal intensity throughout the entire corpus callosum. After high-dose corticosteroid administration her symptoms rapidly resolved, in parallel with the reversion of MRI changes, except for severe cognitive impairment. Follow-up TMS examination revealed persistent transcallosal inhibition (TI) abnormalities. This report indicates that the measurement of TI during the course of MB syndrome is useful for evaluating functional changes to the corpus callosum, including their evaluation with time and after treatment and for elucidating the pathophysiology of MB syndrome.

VIM thalamic stimulation for tremor in a patient with IgM paraproteinaemic demyelinating neuropathy.

We demonstrate the effect of deep brain stimulation of the ventral intermediate thalamic nucleus on intractable action tremor, in a 72-year-old man suffering from neuropathy associated with monoclonal gammopathy.

A patient with delayed posthypoxic demyelination: a case report of hyperbaric oxygen treatment.

A 62-year-old man who developed akinetic mutism with delayed white matter demyelination after hypoxia was treated with hyperbaric oxygen (HBO). HBO in the subacute period markedly improved the patient's activity in daily life, cognitive function and organization on EEG. 1H-MRS showed a recovery of aerobic metabolism of the neurons. However, dementia and cerebral atrophy slowly progressed despite HBO treatment. Thus, HBO had a beneficial effect on the activity of depressed neurons but did not improve the prognosis.