Dystonia in central pontine myelinolysis without evidence of extrapontine myelinolysis.

A 44-year-old female is described who developed persistent upper extremity and orolingual dystonia several weeks after suspected onset of central pontine myelinolysis (CPM), later confirmed by characteristic pontine lesions on MRI. No foci of the extrapontine myelinolysis were evident. This case confirms that dystonia may be a late and persistent sequela of CPM and may occur in the absence of visible lesions outside the brainstem.     

Mild central pontine myelinolysis: a frequently undetected syndrome

Summary Over a period of 1 year we diagnosed central pontine myelinolysis (CPM) in five patients all of whom survived, two of them with complete functional recovery despite extensive lesions on cranial computerized tomography and magnetic resonance imaging.Diagnosis was based upon the combination of an acute brainstem dysfunction with typical neuroradiological features; a history of chronic alcoholism or a preceding hyponatremia may serve as a diagnostic hint.The spectrum of symptoms ranged from severe tetraplegia and cranial nerve palsies to latent signs of pyramidal tract lesions and discrete ocular motor abnormalities. In two patients pontine and extrapontine manifestations of demyelination were confirmed neuroradiologically; in one patient a solely extrapontine manifestation was present.Thus it is reasonable that: (1) the incidence of comparatively mild forms of CPM as well as extrapontine manifestations are more frequent than hitherto assumed, (2) the clinical outcome of the syndrome is better than expected from earlier fatal case reports and is quite independent of the extent of the lesion as it appears with brain imaging methods.     

Extrapontine myelinolysis with involvement of the hippocampus in three children with severe hypernatremia

Central pontine myelinolysis is a disorder of unknown etiology linked to overly aggressive correction of hyponatremia. In addition to the typical location of demyelination with preservation of neurons and axon cylinders in the basis pontis, similar lesions have been described in extrapontine locations. Central pontine myelinolysis and extrapontine myelinolysis usually occur together, and are identified at autopsy rather than in life because symptoms of extrapontine myelinolysis are often masked in the critically ill patient. Central pontine myelinolysis is described in children, usually in the clinical setting of hyponatremic dehydration. Extrapontine myelinolysis has not been described in children previously. We report three children with severe hypernatremia and extrapontine myelinolysis involving various combinations of thalamus, basal ganglia, external and extreme capsules, and cerebellar vermis. All three had additional involvement of the hippocampus seen on T2-weighted magnetic resonance imaging. None of the three had detectable pontine lesions. Clinical features of the three cases were dehydration in a 28-month-old girl, respiratory syncytial virus bronchiolitis in a 14-month-old girl, and acute respiratory failure due to anaphylaxis after consumption of walnuts in a 3-year-old boy. Peak sodium values in each child were 195, 168, and 177 mmol/L, respectively; each received aggressive treatment for hypernatremia. We believe this to be the first report of extrapontine myelinolysis in children, the first report of extrapontine myelinolysis without central pontine myelinolysis in children, and the first report in children of hippocampal formation involvement. The pathogenesis of the central and extrapontine myelinolysis complex in children is more complicated than previously believed, and might differ significantly from that of adults.     

脑桥中央髓鞘溶解症和脑桥外髓鞘溶解症5例临床分析

目的　探讨脑桥中央髓鞘溶解症 (CPM)和 /或脑桥外髓鞘溶解症 (EPM)的发病机制及早期预防和诊治原则。方法　对 5例CPM/EPM患者的临床表现、影像学资料及治疗转归进行分析。结果　临床观察发现 :(1)5例患者均存在严重的基础疾病 ,特别是严重的电解质紊乱 (低钠血症 ) ,不同程度的意识障碍 ,吞咽困难 ,构音障碍。 (2 ) 3例有四肢瘫 ,锥体束征阳性 ;1例表现为帕金森综合征。 (3) 5例头颅MRI均阳性。 (4) 5例均临床好转出院 ,生活自理。结论　 (1)CPM和 /或EPM的发生与低钠血症及快速纠正低钠血症有关。 (2 )CPM和 /或EPM并非致死性疾病 ,无论病情多严重 ,均不应放弃治疗。     

Belly dancer's syndrome following central pontine and extrapontine myelinolysis.

We report on a woman with delayed-onset of belly dancer's syndrome 5 months after central pontine and extrapontine myelinolysis (CPM/EPM) and severe hyponatriemia. This case demonstrates that basal ganglia lesions in EPM can be the underlying pathoanatomic substrate for the rarely observed belly dancer's syndrome. The sequential appearance of extrapyramidal symptoms might reflect an ongoing but ineffective or deficient remyelination process. The presence of CPM/EPM should be considered in patients with involuntary dyskinesias of the abdominal wall.     

Central pontine myelinolysis after liver transplantation

Eight adults and 3 children out of 85 patients who had neuropathologic examination after death following orthotopic liver transplantation showed central pontine myelinolysis (CPM). Four patients also had extrapontine myelinolysis. Eight patients had significant serum sodium changes. In 5, the fluctuation occurred perioperatively and 4 had a clinical picture consistent with CPM, although no patient had this as an antemortem diagnosis. We emphasize the role of hepatic dysfunction as a cause of CPM and recommend careful monitoring of electrolytes in the perioperative period of patients undergoing liver transplantation.     

Central pontine myelinolysis

Summary Thirty-seven cases of central pontine myelinolysis (CPM) with miscellaneous underlying disorders were found in 1,000 consecutive autopsies, of which 636 brains were examined. The incidence of CPM in this study was 5.8%. The frequent underlying disorders were malignant neoplasms (43%), chronic pulmonary disease (27%), and chronic renal failure cases under dialysis treatment (14%). Fatty liver cirrhosis due to alcohol abuse was recognized in only one CPM case. In the present study, 78% of the CPM cases revealed either electrolyte disturbances or abnormal blood gas data, such as marked deviation of base excess and/or of serum pH in 62.5%, hyper- or hypochloremia (above 115 mEq/l, below 95 mEq/l) in 47%, hyper- or hyponatremia (above 150 mEq/l, below 130 mEq/l) in 25%, marked hypoxemia (less than 40 mmHg) in 12.5% and hypokalemia (below 3.0 mEq/l) in 9% of the CPM cases. The myelinolytic changes were localized in the basis pontis in 14 of 37 CPM cases and in the basis pontis and the cerebral and/or cerebellar white matter (extrapontine myelinolysis) in the remaining 23 cases. The extrapontine changes were also closely related to the electrolyte disturbances or the abnormal blood gas data. The results of this study suggest that myclin and oligodendrocytes in the basis pontis and cerebral and cerebellar white matter are vulnerable to abnormal levels of serum electrolytes and also to marked changes of the acid-base balance.     

Central pontine myelinolysis.

Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with demyelination of other areas of the central nervous system (CNS). The term 'osmotic demyelinization syndrome' is used for pontine and extrapontine myelinolysis. In this paper, we are concerned with CPM although the extrapontine one is based on the same pathogenesis. Both share the diagnostic methods, and their prevention and therapy are the same. The etiology and pathogenesis of this disorder are unclear and will be discussed. However, almost all cases of CPM are related to severe diseases. Chronic alcoholism is still the most common underlying condition of CPM patients. In the literature, 174 cases of CPM have been reported in alcoholics since 1986, which is equivalent to an incidence of 39.4%. Likewise, 95 cases of CPM following the correction of hyponatremia have been documented since 1986 (21.5%). The role of hyponatremia and its correction will be outlined in the discussion of the pathogenesis of CPM. The third largest group of CPM cases are liver transplant patients (17.4%), with the development of CPM being attributed to the immunosuppressive agent cyclosporine in particular. Depending on the involvement of other CNS structures, the clinical picture can vary considerably. The large-scale introduction of magnetic resonance imaging has increasingly facilitated the antemortem diagnosis of CPM, although the radiological findings lag behind and do not necessarily correlate with the clinical picture. As yet, there is no specific therapy of choice. A number of therapeutic approaches have been tested and although they have not been compared with regard to their rate of success, they have all led to a substantial improvement in the prognosis of CPM.     

Central pontine and extrapontine myelinolysis owing to disequilibrium syndrome

Neurologic disorders can be seen in patients with end-stage renal failure owing to complications of hemodialysis or peritoneal dialysis. The disequilibrium syndrome can be seen, usually soon after or toward the end of dialysis. We report a patient with central pontine and extrapontine myelinolysis owing to disequilibrium syndrome. The patient had depressed consciousness, agitation, tremor, stupor and hyperactive deep tendon reflexes toward the end of the second peritoneal dialysis. A brain computed tomographic (CT) scan showed hypodense lesions in pontine and extrapontine locations without radiocontrast medium enhancement After 2 days, the patient had only minimal memory deficits. A control brain CT scan 1 week later showed a decrease of the lesions in central pontine and extrapontine locations. Central pontine and extrapontine myelinolysis should be suspected and investigated in the acute neurologic disorders of dialysis patients.     

Extrapontine myelinolysis in a pediatric case of diabetic ketoacidosis and cerebral edema

Central pontine and extrapontine myelinolysis are characterized by symmetric demyelination following rapid shifts in serum osmolality, although in extrapontine myelinolysis, demyelination is confined to the supratentorial compartment. We present a case of extrapontine myelinolysis in a 17-year-old female that occurred in the setting of diabetic ketoacidosis, cerebral edema, mannitol therapy, and meningitis. The rate of correction of this patient's glucose and electrolyte levels was within well-accepted limits. Extrapontine myelinolysis is rare in pediatric patients: there are only 12 reports of extrapontine myelinolysis in children under age 20 years and no pediatric cases of extrapontine myelinolysis or central pontine myelinolysis associated with diabetic ketoacidosis. We review the published cases of extrapontine myelinolysis and examine the underlying etiologies and electrolyte disturbances that characterize these cases. This case expands the list of conditions in which extrapontine myelinolysis occurs to include pediatric patients with complicated diabetic ketoacidosis, emphasizing the importance of sudden osmolar shifts in the genesis of this disorder.     

EXTENSIVE EXTRAPONTINE AND CENTRAL PONTINE MYELINOLYSIS ASSOCIATED WITH CORRECTION OF PROFOUND HYPONATRAEMIA

The relationship between correction of hyponatraemia and the development of central pontine myelinolysis (CPM) remains controversial. A case of CPM associated with extensive extrapontine demyelination is described. Profound hyponatraemia and its subsequent correction are documented. It is suggested that the extent of demyelination reflects the degree of hyponatraemia noted prior to correction, supporting current hypotheses regarding the role of hyponatraemia in CPM. This case is unusual in that other recognized risk factors for the development of CPM are absent.     

Parkinsonism after correction of hyponatremia with radiological central pontine myelinolysis and changes in the basal ganglia.

Parkinsonism has been rarely described following central pontine and extrapontine myelinolysis. We report a case of parkinsonism developing following rapid correction of hyponatremia with radiological evidence of central pontine myelinolysis and changes in the basal ganglia. A 56-year-old man developed drooling and bilateral hand tremors 3 weeks after correction of hyponatremia from 103 to 125 mmol/L over 14 h. He had a prominent 6 Hz resting tremor which worsened with action and mild cogwheel rigidity. Magnetic resonance imaging (MRI) showed changes consistent with central pontine myelinolysis and increased signal on T1-weighted images in the putamen bilaterally. His tremor responded well to L-dopa therapy. There have been several other cases of parkinsonism developing after central pontine/extrapontine myelinolysis. Increased signal in the basal ganglia on T1-weighted images has been described in another case of central pontine myelinolysis imaged about the same time after sodium correction as our case.     

脑桥中央和脑桥外髓鞘溶解症的临床分析和影像特点

目的:探讨脑桥中央和脑桥外髓鞘溶解症的临床及神经影像特点。方法:分析3例脑桥中央髓鞘溶解症和1例脑桥外髓鞘溶解症患者的临床特点,包括起病前诱因、临床表现、头颅MRI特点、治疗及预后情况。结果:4例患者均有慢性形成低钠血症后被快速纠正的病史,以意识改变、构音和吞咽困难、四肢瘫痪等为临床表现。3例脑桥中央髓鞘溶解症的MRI表现为脑桥部位对称性的T1加权低信号灶、T2加权高信号灶,呈环状分布;1例脑桥外髓鞘溶解症者在基底节区域有对称性的T1加权低信号、T2加权高信号病灶。4例患者总体预后良好。结论:提高髓鞘溶解症的认识对于本病的防治非常重要,缓慢纠正慢性形成的低钠血症是预防的关键。     

A case report of central pontine and extrapontine myelinolysis which occurred during pregnancy and was accompanied by choreic movement

A 25-year-old female in the 17th week of pregnancy was diagnosed by MRI as having central pontine and extrapontine myelinolysis. Serial observations with MR showed gradual disappearance of the lesions in the pons and striatum. Improvement of the symptoms took place shortly before disappearance of the lesions on MRI pictures. The initial symptoms were consciousness disturbance, cranial nerve palsy and tetraparesis. Before the latter disappeared seven months after occurrence of the disease, all other symptoms gradually improved. They were followed by delayed appearance of choreic movements, which was still remaining one year after discharge. It is rare for a pregnant woman to be attacked by central pontine myelinolysis. Moreover, very few symptoms caused by such extrapontine lesions have so far been reported. Also, a review of the relevant literature by the authors found no other case showing choreic movements. This report is of an extremely rare case of central pontine and extrapontine myelinolysis which occurred during pregnancy and is accompanied by choreic movements.     

Symptomatic hyponatraemia: can myelinolysis be prevented by treatment?

The treatment of hyponatraemia is controversial because of the risk of causing central or extrapontine myelinolysis (EPM). Rapid correction with hypertonic saline to a low normal sodium level has its proponents; others feel that slow correction to below normal sodium values is preventative. Most investigators feel that overcorrection should be avoided. It is not known whether the magnitude of serum sodium change is more important than the actual rate of correction. We present three patients with hyponatraemia ranging from 103 to 105 mmol/l who were corrected slowly with normal saline, corrected quickly with hypertonic saline, or rapidly overcorrected with hypertonic saline. All became comatose and died; all had EPM with or without central pontine myelinolysis (CPM). The rate of correction, the solution used, or the magnitude of correction did not seem to protect against demyelination. In a review of 67 reported CPM cases since 1983, no patients documented as having CPM or EPM by radiological studies or necropsy were treated with water restriction only. A group of 27 hyponatraemic patients treated only with water restriction and 35 with diuretic cessation alone did not develop CPM or EPM. This may be a reasonable approach to patients with symptomatic hyponatraemia and normal renal function.     

Magnetic resonance imaging in central pontine myelinolysis.

Magnetic resonance imaging (MRI) was performed in two patients in whom a clinical diagnosis of central pontine myelinolysis (CPM) had been made. MRI showed lesions in the pons in both cases about 2 years after the illness, at a time when the spastic quadriparesis and pseudobulbar palsy had recovered. The persisting abnormal signals in CPM are likely to be due to fibrillary gliosis. Persistence of lesions on MRI means that the diagnosis of CPM may be electively, after the acute illness has resolved.     

Diffusion-weighted MR findings of central pontine and extrapontine myelinolysis

Diffusion-weighted MR (DWI) can detect changes in water diffusion associated with cellular dysfunction, which enables the differentiation of cytotoxic edema from vasogenic edema. In this study on DWI findings in central pontine (CPM) and extrapontine myelinolysis (EPM), DWI showed high signal intensities in the bilateral pons, midbrain, and genu of the corpus callosum. The corresponding apparent diffusion coefficient values were rather low. This suggests that cytotoxic edema does in fact exist in CPM and EPM and that DWI can be useful in the rapid diagnosis and prediction of the various types of edema occurring in active demyelinating diseases.     

A case of alcoholic with vitamin B12 deficiency presenting central pontine and extrapontine myelinolysis on MRI]

A 55-year-old man with chronic alcoholism was first referred to us in 1992 because of spastic quadriparesis. T2-weighted images of MRI showed pontine and extracapsule lesions as central pontine and extrapontine myelinolysis (CPM/EPM). He had macrocytic anemia with normal serum level of vitamin B12 (B12). Gait disturbance was progressively worsened from the end of 2004 and dysuria appeared from June, 2005. Neurological examination on admission in November, 2005, showed mild impairment of recent memory, spastic paraparesis with hyperreflexia in all limbs, loss of deep sensations in lower limbs and urinary disturbance. The low serum level of B12 with marked macrocytic anemia was noted. On MRI. the pontine lesion extended to the midbrain but no abnormality was found in the spinal cord. We intramuscularly administered B12, resulting in marked improvement of both anemia and neurological symptoms. The brainstem lesion on MRI, however, was unchanged. We assume that B12 deficiency was involved in the formation of CPM/EPM and the neurological symptoms in our patient.     

Sequential observation of movement disorders and brain images in the case of central pontine myelinolysis and extrapontine myelinolysis

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are well recognized syndromes related to rapid correction of hyponatremia and have been reported to show a variety of movement disorders. However, sequential observation of movement disorders as well as brain images has seldom been reported. We report a case of CPM and EPM presenting with various sequential changes in movement disorders including delayed choreic movement over 11 months; we present sequential brain magnetic resonance images showing increased T1 and decreased fat-suppression T1 signal intensity. We suggest that delayed low signal intensity, in the fat-suppression T1-weighted images, is a result of the destruction of myelin and by products. Damage to the myelin may cause various movement disorders in a delayed manner.     

Central pontine myelinolysis, an update

Central pontine myelinolysis (CPM) can be regarded as one of the demyelinating syndromes. First described by Adams et al. in 1959 in their chronic alcoholic patients, it has now been described in the malnourished, the chronically debilitated, the renal, the hepatic and the transplant patient among others. Pathologically, it is defined as a symmetric area of myelin disruption in the center of the basis pontis, although similar symmetric lesions have also been described occurring with CPM as well as independently in other brain areas (extrapontine myelinolysis or EPM) including the cerebellar and neocortical white/gray junctional areas, thalamus and striatum. Possible mechanisms include a hyperosmotically induced demyelination process resulting from rapid intracellular/ extracellular to intravascular water shifts producing relative glial dehydration and myelin degradation and/or oligodendroglial apoptosis. The process most often occurs during rapid rebalancing of the electrolyte parameters in the hyponatremic patient. Avoidance of CPM/EPM is dependent upon recognizing those patients with conditions pre-disposing them to osmotic myelinolysis and then moderating the rate of normalization of the electrolyte imbalance. The morbidity and mortality of CPM/EPM has been greatly reduced by recognition of pre-disposing conditions, increased understanding of the pathophysiology, intensive treatment, and rapid diagnosis and monitoring with advanced neuroimaging.