Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per Day.

Background: Overly rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome. European guidelines recommend a correction to ≤10 mEq/L in 24 hours to prevent this complication. However, osmotic demyelination syndrome may occur despite adherence to these guidelines. Methods: We searched the literature for reports of osmotic demyelination syndrome with rates of correction of hyponatremia ≤10 mEq/L in 24 hours. The reports were reviewed to identify specific risk factors for this complication. Results: We identified 19 publications with a total of 21 patients that were included in our analysis. The mean age was 52 years, of which 67% were male. All of the patients had community-acquired chronic hyponatremia. Twelve patients had an initial serum sodium <115 mEq/L, of which seven had an initial serum sodium ≤105 mEq/L. Other risk factors identified included alcohol use disorder (n=11), hypokalemia (n=5), liver disease (n=6), and malnutrition (n=11). The maximum rate of correction in patients with serum sodium <115 mEq/L was at least 8 mEq/L in all but one patient. In contrast, correction was <8 mEq/L in all but two patients with serum sodium ≥115 mEq/L. Among the latter group, osmotic demyelination syndrome developed before hospital admission or was unrelated to hyponatremia overcorrection. Four patients died (19%), five had full recovery (24%), and nine (42%) had varying degrees of residual neurologic deficits. Conclusion: Osmotic demyelination syndrome can occur in patients with chronic hyponatremia with a serum sodium <115 mEq/L, despite rates of serum sodium correction ≤10 mEq/L in 24 hours. In patients with severe hyponatremia and high-risk features, especially those with serum sodium <115 mEq/L, we recommend limiting serum sodium correction to <8 mEq/L. Thiamine supplementation is advisable for any patient with hyponatremia whose dietary intake has been poor.

Presence of White Matter Lesions Associated with Diabetes-Associated Cognitive Decline in Male Rat Models of Pre-Type 2 Diabetes.

BACKGROUND The aim of this study was to determine the association between white matter lesions (WML) and diabetes-associated cognitive decline (DACD) in rat models of type 2 diabetes (T2DM). MATERIAL AND METHODS Sixty Sprague-Dawley male rats were divided into 4 groups: control, control+metformin, T2DM, and T2DM+metformin groups. The T2DM groups were fed a diet high in fat and glucose to induce impaired glucose tolerance (IGT) and then were injected with streptozotocin to induce T2DM. The Morris water maze test was used to evaluate cognitive function. Brain diffusion tensor imaging scans were performed for WML. The expression of myelin basic protein (MBP), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (markers of brain damage and repair) was determined using immunofluorescence. After IGT, the fractional anisotropy (FA) values of the right thalamus area were significantly lower in both T2DM groups compared with controls. RESULTS Eight weeks after streptozotocin injection, the FA values of the thalamus were lower in the T2DM (bilateral thalamus) group and T2DM+metformin (left thalamus) group than in controls, while the FA values in the left thalamus area were lower in the T2DM+metformin group than in the control and control+metformin groups. The maze escape latency was longer and the number of rats passing through the platform was smaller in the T2DM and T2DM+metformin groups than in the control group. MBP levels were lower and OLIG1 and OLIG2 levels were higher in both T2DM groups than in controls. CONCLUSIONS WML is associated with DACD and appears before the onset of T2DM and signs of DACD and plays a role in diabetes-associated cognitive decline. Metformin reduces WMLs but does not rescue cognitive dysfunction.

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.

Hypothalamic demyelination causing panhypopituitarism.

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed.

Does vitamin D deficiency predict early conversion of clinically isolated syndrome? A preliminary Egyptian study.

BACKGROUND: It has been suggested that vitamin D influences the immunoregulation and subsequently affects the risk for conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS). There is little information regarding the relationship between levels of vitamin D and CIS conversion to MS in Egyptian patients. OBJECTIVE: It is to study contribution of vitamin D deficiency to conversion of CIS to clinically definite multiple sclerosis (CDMS) and correlation of vitamin D level to cognitive and magnetic resonance imaging (MRI) results. PATIENTS AND METHODS: A longitudinal prospective case control study was conducted on 43 Egyptian patients diagnosed as CIS according to McDonald criteria (2010). Clinical presentation, brain MRI and 25-hydroxyvitamin D levels were evaluated at baseline and after one-year follow-up. RESULTS: The CIS patients that converted to MS showed significant lower vitamin D level (p < 0.001) than the non-convertors. Multivariate logistic regression analysis revealed that the CIS patients with lower 25-hydroxyvitamin D level (p < 0.001) are at higher risk for early conversion to MS. There was a significant positive correlation between the vitamin D level and PASAT (r = 0.36, p = 0.02). It was found that there was a significant negative correlation between vitamin D level and MRI T2 load (r = -0.38, p = 0.01). CONCLUSION: The low level of 25-hydroxyvitamin D may predict early conversion to clinically definite MS. Early vitamin D supplementation is recommended in patients with CIS.

An unusual cause of falls in a young woman.

Nitrous oxide is commonly used as an analgesic and anaesthetic agent. Nitrous oxide is also in use in industry as an aerosol propellant and is now recognised as a recreational drug whose use is growing, especially among the young. Nitrous oxide from whipped cream canisters is inhaled to produce a dissociative, intoxicated state. Nitrous oxide is known to inactivate vitamin B12 via oxidation, which can precipitate a demyelinating myelopathy akin to the classical B12 deficiency syndrome, subacute combined degeneration of the spinal cord. This case describes a young woman with chronic pain and a poor nutritional state who took regular nitrous oxide as an opiate-sparing agent. She developed a progressive subacute myelopathy with a sensory level, profoundly impaired joint position sense, extensor plantars and required a wheelchair. Once diagnosed, she responded well to a regime of nitrous oxide withdrawal, high-dose B12 replacement and physiotherapy. The case illustrates the need for clinical teams to be able to dentify a nitrous oxide-precipitated myelopathy as its use as a drug of abuse increases; particularly in the case of malnourished patients who receive nitrous oxide surgically or obstetrically.

Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells.

The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1ß), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.

Thalamic lesions: a radiological review.

BACKGROUND: Thalamic lesions are seen in a multitude of disorders including vascular diseases, metabolic disorders, inflammatory diseases, trauma, tumours, and infections. In some diseases, thalamic involvement is typical and sometimes isolated, while in other diseases thalamic lesions are observed only occasionally (often in the presence of other typical extrathalamic lesions). SUMMARY: In this review, we will mainly discuss the MRI characteristics of thalamic lesions. Identification of the origin of the thalamic lesion depends on the exact localisation inside the thalamus, the presence of extrathalamic lesions, the signal changes on different MRI sequences, the evolution of the radiological abnormalities over time, the history and clinical state of the patient, and other radiological and nonradiological examinations.

Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event: results from the multi-center set study.

OBJECTIVES: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months. RESULTS: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. CONCLUSIONS: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

Thalamic atrophy and cognitive impairment in clinically isolated syndrome and multiple sclerosis.

BACKGROUND: Cognitive deficits worsen the quality of life in multiple sclerosis and may be predicted by deep gray matter atrophy, especially thalamic atrophy. This relationship has not been studied in the clinically isolated syndrome (CIS). The aims of this study were to assess cognitive deficits in patients with CIS and relapsing-remitting multiple sclerosis (RRMS) using neuropsychological testing, to search for thalamic atrophy on brain MRI, and to test for their correlations. METHODS: Forty-three patients (19 with CIS and 24 with RRMS) underwent brain MRI and neuropsychological testing involving multiple cognitive domains and the severity of depression. Thalamic volumes automatically segmented from MRI data were compared to 19 healthy controls. Correlations were sought between cognitive performance and thalamic volume. RESULTS: Cognitive impairment was detected in the majority of both CIS and MS patients, most affected in executive functions, auditory memory, lexical verbal fluency, distribution of attention and psychomotor speed. Cognitive impairment and depression were not significantly correlated to disease duration. Both CIS and MS patients demonstrated thalamic atrophy compared to controls, while many cognitive deficits correlated with thalamic volume in both patient groups. CONCLUSION: Cognitive deficits in CIS resemble those found in the later stages of MS and may be directly related to the amount of thalamic damage.

Efectos adversos observados durante la terapia biológica en la psoriasis. Resultados de una encuesta al Grupo Español de Psoriasis / Adverse reactions during biological therapy for psoriasis: results of a survey of the Spanish Psoriasis Group

Introducción: La terapia biológica ha representado un avance muy importante en el tratamiento de la psoriasis, al tratarse de una generación de fármacos más selectivos y con mejor perfil de seguridad a corto y medio plazo. Existen datos sólidos a favor de la eficacia de cada uno de estos fármacos, así como de su seguridad. A pesar de ello, siempre es útil aportar la experiencia clínica de dermatólogos expertos en el tratamiento de la psoriasis con biológicos, en especial en lo referente a su seguridad. Material y métodos: Se realizó una encuesta a los miembros del Grupo Español de Psoriasis (GEP) basada en una serie de ítems relativos a aspectos referentes a la seguridad clínica de estos fármacos, cuyos resultados se presentan en este artículo. Un total de 988 pacientes tratados con efalizumab, etanercept, infliximab y adalimumab fueron recogidos por parte de 15 miembros del GEP. Resultados: Entre los resultados obtenidos destaca la elevada proporción de reacciones a infliximab (34%). Se observaron alteraciones analíticas en el 13,25% de los pacientes e infecciones en el 12,24%, con un único caso de tuberculosis pulmonar. Es de destacar el perfil de efectos secundarios de efalizumab: artritis de novo en el 5,8% y rebote en el 20,9%. Conclusión: Los datos de seguridad aportados por nuestro trabajo deben tenerse en consideración, habida cuenta del importante número de pacientes reclutados por un grupo de dermatólogos expertos en el manejo de este tipo de fármacos (AU)

Background: Biologic therapies have been a major breakthrough in the treatment of psoriasis because they are more selective and have a better short-term and medium-term safety profile. There are reliable data to support both the efficacy and the safety of these drugs. However, it is always useful to report the clinical experience of dermatologists who are experts in the use of biologic agents to treat psoriasis, particularly with regard to their safety. Material and Methods: We present the results of a survey administered to the members of Spanish Psoriasis Group and based on a series of questions referring to the clinical safety of these agents. A total of 988 patients treated with efalizumab, infliximab, etanercept, and adalimumab were reported by 15 members of the group. Results: There was a particularly high proportion of reactions (34%) to infliximab infusions. Blood test abnormalities were detected in 13.25% of patients and infections in 12.24%, with one case of pulmonary tuberculosis. Attention is drawn to the adverse effects profile of efalizumab: de novo arthritis in 5.8% and rebound in 20.9% of patients. Conclusion: The safety data provided by our study should be taken into account in view of the large number of patients recruited by dermatologists experienced in the use of this type of therapy (AU)

Effective thalamic deep brain stimulation for neuropathic tremor in a patient with severe demyelinating neuropathy.

Postural and action tremor in peripheral neuropathy is characteristic of Roussy-Levy syndrome. A patient with a severe demyelinating neuropathy and disabling neuropathic tremor successfully treated by deep brain stimulation (DBS) is reported. Disease onset was at age 63 years with sensory symptoms and slight action tremor. Within the following 9 years a severe, drug resistant, postural and action tremor developed rendering the patient unable to feed himself. At age 72 years the patient was treated by bilateral DBS of the ventral intermediate thalamic nucleus, with a useful 30% reduction in tremor. The clinical benefit of the stimulation remained stable over a 1 year postoperative observation period.

Spinal cord demyelination associated with biotinidase deficiency in 3 Chinese patients.

Biotinidase deficiency is a treatable cause of severe neurological disorders and skin problems. Spinal cord impairment is a rare complication of this disease and is commonly unrecognized. The authors encountered 3 Chinese patients with progressive spinal cord demyelination associated with biotinidase deficiency. Case 1 exhibited fatigue, proximal muscular weakness, and hypotonic paraplegia from the age of 7 years 4 months. Demyelination of cervical and thoracic cord was evident on magnetic resonance imaging (MRI). Case 2 developed visual impairment, blepharoconjunctivitis, and optic nerve atrophy from 5 years of age, which combined with progressive hypertonic paralysis, ataxia, and alopecia from the age of 7 years. His spinal MRI T2-weighted sequence revealed an extensive hyperintense lesion involving the cervical spinal cord C(2) to C(4). Bilateral optic nerves were significantly thick. In case 3, intercurrent wheezing, tachypnea, dyspnea, and lethargy occurred from the age of 1 year. Medulla and upper cervical spine edema and demyelination were found on MRI. Markedly elevated urine organic acids and decreased blood biotinidase activities were observed in the 3 patients. Biotin supplementation led to a dramatic improvement of clinical symptoms in 3 patients. The findings indicate that biotinidase deficiency should be considered in the differential diagnosis of unexplained spinal cord demyelination because prompt diagnosis and treatment with biotin may enable an excellent recovery.

Acute pathological laughter.

Pseudobulbar affect is a condition characterized by uncontrollable episodes of inappropriate laughing or crying that are disproportionate and discordant to the situation at hand. We report on a 16-year-old woman presenting with acute pathological laughter in the context of CNS demyelinating disease. Brain MRI scans fortuitously obtained before and after the onset of this symptom demonstrated acute gadolinium-enhancing lesions in the cerebral peduncles. The etiology of this condition remains theoretical; however, the results here provide further insights into the pathways of emotional control.

[A case of fatal hemolytic-uremic syndrome with central nervous system manifestations]. / Przypadek zespolu hemolityczno-mocznicowego ze zmianami w ukladzie nerwowym.

Twelve years old girl who died from haemolytic uraemic syndrome (hus) on post mortem neuropathological examination showed cerebral purpura and demyelination focus with glial-mesenchymal reaction. The problem with factor is responsible for cerebral lesions, direct allergic reaction causing hus or uraemia in consequence of acute renal failure but also activating allergic processes, is discussed.

Lateral pontine and extrapontine myelinolysis associated with hypernatremia and hyperglycemia.

Efforts to understand and prevent pontine and extrapontine myelinolysis have focused on the correction of hyponatremia, but controversy persists. We report a woman who presented in hyperosmolar diabetic coma with hypernatremia (169 mEq/l) and hyperglycemia (954 mg/dl). Plasma sodium rapidly increased to 188 mEq/l before gradually returning to normal. She remained obtunded and died 21 days later. Autopsy showed widespread, symmetrical demyelination involving the subcortical white matter, corpus callosum, anterior commissure, extreme, external, and internal capsules, fornix, thalamus, cerebellum, and lateral pons. The central pons and lateral geniculate nuclei were uninvolved. This case illustrates that lateral pontine and extrapontine myelinolysis can be associated with hypernatremia and hyperosmolality. In both hypo- and hypernatremic states, the significant event may be an increase in serum sodium or serum osmolality of sufficient rapidity and magnitude.

Lateral hypothalamic demyelination and cachexia in a case of "malignant" multiple sclerosis.

A 41-year old woman had profound weight loss and cachexia as a manifestation of rapidly fatal multiple sclerosis. Demyelinating lesions were present in the lateral hypothalamus. Data from animal experiments have indicated that lateral hypothalamic lesions cause a weight loss associated with a lowering of the regulation level or "set-point" for body weight. This case suggests, therefore, that a rapid decline in the level of maintained body weight in a patient without pituitary disease or general organic disorder, or distinct emotional disorder, may represent a clinical manifestation of tissue injury of the lateral hypothalamus.