Osmotic demyelination syndrome (ODS), also known as osmotic myelinolysis syndrome (OMS), is a rare acute noninflammatory central demyelinating disease, mainly due to chronic hyponatremia in which brain cells have adapted to a hypotonic state. It is a rare acute non-inflammatory central demyelinating disease, mainly due to chronic hyponatremia in which brain cells have adapted to a hypotonic state. The first detailed report of symmetric non-inflammatory myelinolysis in the central pontine was reported by Adams in 1959 and named central pontine myelinolysis (CPM) in 1962. In 1962, it was discovered that myelin loss lesions could also involve other parts of the brain outside the pons, such as the basal ganglia, thalamus, and subcortical white matter, and similar pathological changes and corresponding clinical symptoms and signs could occur, accounting for about 10% of CPM, called extrapontine myelinolysis (EPM). This disease is rare, and the etiology is uncertain, and it may occur in various clinical departments. Wang Aihua, Department of Neurology, Shandong Province Qianfo Mountain Hospital
1 Etiology
Chronic alcoholism and malnutrition are the more certain etiologies, accounting for about 39%. And the over-correction of hyponatremia became the second cause after 1986, accounting for about 21.5%. Diseases causing hyponatremia include liver cirrhosis, massive rehydration, drug addiction, abnormal syndrome of anti-diuretic hormone secretion, pituitary surgery, lung and intestinal cancer, and long-term use of diuretics. In the same year, 17% of CPM was reported to be caused by liver transplantation, making it the third leading cause. The main factors, especially within 30 days after liver transplantation, include sepsis, metabolic disorders, hepatic encephalopathy, hypoxia, tacrolimus and cyclosporine use. burns, AIDS, pregnancy hyperemesis, central nervous system dry syndrome, systemic lupus erythematosus, cytomegalovirus hepatitis, EBV-associated phagocytic syndrome, anaphylaxis, heat stroke, psychogenic irritability, anorexia nervosa, post-hematopoietic stem cell transplantation for acute lymphoblastic leukemia, post-hemodialysis for uremic syndrome, post-therapy for hyperammonia due to ornithine transcarbamylase deficiency and antidiuretic hormone ODS due to receptor deficiency has been reported in recent years. Recently, folic acid deficiency and reduced blood phosphate have been suggested as associated factors, and drugs (diuretics, growth inhibitors, hypoglycemic agents, antidepressants, barbiturates, antamine, parenteral magnesium preparations, arginine overdose, lithium toxicity, etc.) can cause the sudden onset of ODS in healthy patients.
2 Pathogenesis
The pathogenesis of the disease is still unclear, but many believe that it is related to the destruction of BBB, osmotic damage of endothelial cells and myelin toxicity due to harmful metabolism of oligodendrocytes, Norenberg believes that myelin toxicity originates from the vascular-rich gray matter (including the basal ganglia and thalamus), and these gray matters and the adjacent white matter surrounded by a large amount of gray matter (such as gyrus, internal capsule, external capsule, outermost capsule, etc.) Riggs et al. suggested that osmotic pressure and oligodendrocyte distribution are more important than the rapid correction of low sodium, because rapid changes in serum osmolality are more likely to contribute to the development of ODS, whether low or high sodium. , as in patients with chronic alcoholism or liver disease, mostly lacking sufficient glucose and hepatic glycogen to maintain glial cell Na+-K+ ATPase pump activity, leading to electrolyte disturbances in the brain, which are exacerbated by reduced glucose uptake by the brain due to VitB1 deficiency. Neurons release glutamates and other excitatory substances when osmolality is altered, Ca2+ channels are altered and intracellular Ca2+ concentration increases causing apoptosis.Silver et al. proposed that there is a close correlation with organic osmolytes, not only electrolytes are altered in low sodium, but also organic osmolytes such as amino acids (e.g. alanine, glutamate, taurine, glycine) and sugars (e.g. inositol) are altered, and rapid correction of low sodium restores intracellular electrolytes quickly, but is unable to correct the lost organic osmolytes quickly, leading to cell damage and demyelination. In experimental animal models, it was found that the brain regions with the slowest recovery of organic osmolality after rapid correction of hyponatremia were the most severely demyelinated. Patients with alcoholism and malnutrition are generally deficient in organic osmolytes, which places them in a high-risk environment of cellular crumpling and makes the gray matter adjacent to blood vessels more susceptible to damage when blood sodium is reduced, leaving the cerebral bridge particularly vulnerable to myelin toxicity leaking from the vessels. However, these mechanisms are not well understood and further studies are needed to confirm them.
3 Clinical manifestations and diagnosis
3.1 Clinical manifestations
CPM is characterized by tetraplegia and different degrees of brainstem dysfunction, such as pseudomyelitis, occasionally atresia syndrome, mutism, etc. EPM is mainly characterized by dyskinesia, dystonia, Parkinson’s syndrome, etc. It is rare to see only cerebellar signs. Hawthorne et al. recently reported a case of midbrain damage such as actinic nerve palsy, imaging abnormalities and rotational nystagmus after too rapid correction of hyponatremia. If there is a history of rapid correction of hyponatremia, symptoms often appear within 2-7 days after correction. ods is often accompanied by psychiatric symptoms such as abnormal behavior, cognitive and emotional disturbances, nervousness, emotional instability, muteness, excitement, delusions, and hallucinations, suggesting frontal lobe damage.
3.2 Imaging features
ODS appears on CT as a hypointense shadow at the central pontine or extra-pontine lesions, but CT cannot reflect the true extent of the disease, and MRI can better reflect the number and extent of lesions. In the early stage, there may be no abnormality, and high signal may be found on DWI 1 week after the onset of symptoms. The acute phase shows symmetric T1WI low signal, and the subacute phase may show T2WI high signal due to microhemorrhage caused by endothelial cell damage. FLAIR shows lesion high signal more clearly and can better show lesions in the adjacent cerebrospinal fluid, such as the cerebral cortex, and should be used as a routine examination. There are also some reports finding cortical and subcortical T1 high signal, with or without gadolinium enhancement being reinforced. MRI of the brain is very important for the diagnosis of this disease, and the abnormal signal is most obvious at about 2 to 3 weeks after the onset of the disease. Therefore, if the diagnosis of ODS is considered in combination with the medical history and clinical manifestations, it is important and necessary to review MRI 10 to 14 days after the onset of symptoms if the MRI examination is normal. MRI follow-up can dynamically observe the lesions and changes in surface diffusion coefficient (ADC), and MRS or PWI can also be performed to establish complete and comprehensive imaging information to assist in diagnosis, guide treatment, and predict prognosis.
3.3 Diagnosis
In the past, the diagnosis of ODS mainly relied on autopsy, but with the widespread use of MRI, prenatal diagnosis has become possible, and the early diagnosis rate has been greatly improved. If the patient has a history of chronic alcoholism, rapid correction of hyponatremia, liver transplantation and other serious diseases, sudden onset of pseudomyelitis, atresia syndrome, mutism, impaired consciousness, damage to the corticospinal tract and corticobulbar tract or motor disorders, muscle Once a triangular to batwing-shaped lesion with T1WI low signal, T2WI and DWI high signal in the central part of the symmetrical cerebral bridge appears, there is a diagnostic significance of CPM, while T1WI low signal and T2WI high signal in the striatum and thalamus on both sides, especially in the region of the nucleus accumbens and the nucleus accumbens, suggest EPM, and also symmetrically involve the corpus callosum, subcortical white matter, cerebellum or cerebellar peduncle, lateral geniculate body, and substantia nigra. In conclusion, the diagnosis is based on clinical suspicion of ODS and confirmation of MRI findings. We know that T1WI low signal and T2WI high signal can be seen in ischemia, multiple sclerosis, tumors and metabolic diseases, and that ODS is symmetrical to help differentiate. Hypoxic metabolic diseases can also show symmetrical changes, and a thorough and accurate history is important. Late onset dentate nucleus pallidus Lewy body atrophy is difficult to differentiate in the absence of prominent white matter encephalopathy with significant cerebral bridge lesions, which are often manifested as cerebellar ataxia, dementia, and chorea. When the lesion involves the cortex, it needs to be differentiated from cortical laminar necrosis, which is characterized by cortical T1WI high signal without enhancement on MRI, and delayed cortical atrophy in the chronic phase, with hypoxia, infarction, epileptic seizures, and drug use as the main causes, however, it has recently been suggested that rapid correction of hyponatremia is the second most likely cause, requiring careful differentiation.
4 Treatment
4.1 Hyponatremia
Rapid correction of hyponatremia has been suggested as a “medical” consequence of ODS, so it is necessary to review the relevant knowledge here. Hyponatremia is defined as serum sodium concentration below 135 mmol/L. Acute hyponatremia is defined as hyponatremia within 48 h or sodium reduction >0.5 mmol/h, while chronic hyponatremia is defined as persistent hyponatremia over 48 h or sodium reduction <0.5 mmol/h. Serum sodium concentration is classified as mild (<125-134 mmol/L), moderate (<120-124 mmol/L), and severe (<120-124 mmol/L). /L), and severe (<120 mmol/L). Symptoms of hyponatremia include headache, weakness, loss of appetite and muscle cramps, and central symptoms include mental depression, nausea, headache, lethargy, confusion, epileptic seizures, coma and even death, and lack of focal neurological signs. Chronic hyponatremia can be asymptomatic.
The current recommended ideal rate of correction of hyponatremia is no more than 8 mmol/L/d or 0.5 mmol/L/h, with an initial rate of sodium replacement of 1 to 2 mmol/L/h. Hypertonic salts are recommended for patients with hyponatremic encephalopathy, but are potentially dangerous, and blood sodium should be monitored at least every 2 h and should not exceed 20 mmol/L for 48 h. However, in any case, asymptomatic patients with no neurological Patients with no neurological involvement should not be given hypertonic sodium infusions, regardless of the amount of sodium. Hypokalemia should be corrected first or simultaneously with hyponatremia. Chronic hyponatremia that is corrected too quickly is at high risk of developing ODS and requires early and accurate analysis.
4.2 Treatment of ODS
There is a lack of effective treatment for ODS. Thyroid-releasing hormone (TRH), steroid hormones, plasma replacement, immunoglobulin and hyperbaric oxygen therapy have been reported. In a 13-year-old girl who developed hyponatremia after surgical treatment for an epidural hematoma and was diagnosed with EPM, Chemaly et al. used TRH 0.6m g/d intravenously for 6 weeks, which improved within a few days of use until complete recovery. in 1993, a 65-year-old male patient with hyponatremia complicated by mitral valve replacement for tendon rupture developed tetraplegia and coma, and was treated with CT and MRI The presence of CPM was confirmed, and Konno et al. treated with TRH resulted in significant improvement of neurological symptoms without any residual neurological deficit symptoms. The possible mechanism is that thyrotropin-releasing hormone enhances the effect of levodopa and increases the local blood supply.
Nishino et al. reported a patient with improvement of CPM symptoms after methylprednisolone administration, and Finsterer et al. asserted that intravenous gammaglobulin 0.4 g/kg reduced myelin toxicity, formed anti-myelin antibodies, and supported myelin regeneration for 5 days. It was effective after 5 days. A 48-year-old patient who developed CPM after correction of hyponatremia was also reported to have improved symptoms after 2 days with the above treatment. Early experiments in animal models confirmed that the use of steroid hormones such as dexamethasone maintained the stability of the BBB thereby reducing edema and damage to oligodendrocytes, reducing the passage of extravascular material through the BBB thereby reducing demyelinated lesions, and affecting the influx and activity of macrophages, which ultimately led to myelinolysis in animal models [1]. The smaller risk of short-term steroid hormone use dictates that this is a feasible treatment and also supports the hypothesis of osmotic endothelial damage.
Plasma exchange has also been used to treat CPM, and three such patients were reported by Bibl et al. One was a 29-year-old female patient who developed hyponatremia after alcohol abuse and developed tetraplegia and ataxia after correction of the hyponatremia. After plasma exchange, first once a day for 4 days and then twice a week for 3 weeks, the total amount of plasma exchanged was 24 700 mL. The tetraplegia resolved after 2 months, but the severe ataxia persisted for about 1 year. The second case was a 20-year-old woman with anorexia nervosa with hyponatremia who developed lethargy with tetraplegia about 5 days after correction of the hyponatremia, and the patient was able to walk 1 month after 5 plasma exchanges totaling 5,234 ml. In the last case, a 30-year-old female patient with mild hyponatremia due to alcohol abuse, mild ataxia symptoms disappeared after 12 months following 7 weeks of plasma exchange totaling 18 270 ml after the diagnosis of CPM. The possible mechanism of plasma exchange for ODS is the removal of myelin toxins, and intravenous application of immunoglobulin reduces myelin toxins and anti-myelin antibodies, and promotes myelin regeneration. If clinically proven to be effective, the future direction of treatment may be based on the hypothesis of abnormal immune mechanisms.
However, the above treatments are reported on a case-by-case basis and the specific mechanisms are not known, and there are no randomized studies to confirm the effectiveness of these treatment modalities, so none of them are recommended for the treatment of ODS. The key is to identify risk factors and prevent too rapid correction of hyponatremia to prevent neurological impairment, especially in severe chronic hyponatremia. High-risk factors include sodium supplementation exceeding 10-15 mmol/L/d, hypoxia, premenopausal women and pediatric patients. It is believed that ODS has many etiologies, so special attention should be paid to high-risk patients, such as patients with sudden changes in blood sodium, liver transplantation, chronic alcoholism and malnutrition, which can avoid triggering ODS.
6 Prognosis
Almost 100% of the early reported CPMs died after 3 months of hospitalization. In recent years, there are some reports of survival or complete recovery with mild neurological deficits left behind. It is generally believed that 1/3 can fully recover, 1/3 are left with some neurological deficits, and 1/3 die. From a neuroimaging point of view, the regression of lesions on MRI takes longer than the course of the disease. the presence or absence of MRI abnormalities is not related to the prognosis of the disease. In the follow-up, it was found that MRI signal could be reduced, completely disappeared or existed throughout life, and there was a close relationship between abnormal ADC values and clinical manifestations, so DWI could help to predict ODS prognosis early.