|Ahead of print publication
Osmotic Demyelination Syndrome Presenting as Extrapontine Myelinolysis with or without Central Pontine Myelinolysis: Case Series of Five Cases and Review of Literature
Saurabh Gupta1, Shikha Gupta2, Akhilesh Shroti1
1 Pacific Centre of Neurosciences, Pacific Medical College and Hospital, Udaipur, Rajasthan, India
2 Department of Medicine, Pacific Medical College and Hospital, Udaipur, Rajasthan, India
|Date of Submission||21-Apr-2021|
|Date of Decision||31-Jul-2021|
|Date of Acceptance||09-Sep-2021|
|Date of Web Publication||13-Nov-2021|
Flat no 2, Teaching Staff Quarter A, Pacific Medical College and Hospital, Udaipur 313011, Rajasthan
Source of Support: None, Conflict of Interest: None
Background and objective: Osmotic demyelination syndrome (ODS) refers to a spectrum of clinicoradiologic syndrome which occurs due to pontine and extrapontine involvement due to myelinolysis. It is well described in association with rapid correction of hyponatremia and in alcoholics. In this case series, we have reviewed clinical presentation, neuroimaging features, and clinical outcomes of five patients diagnosed with ODS. Methods: The hospital medical records of all patients diagnosed with ODS between September 2018 and May 2020 at our hospital were analyzed retrospectively. Patients’ relevant clinical details and laboratory findings were recorded and magnetic resonance imaging (MRI brain) was reviewed. Those cases having imaging or clinical picture not clearly consistent with diagnosis were excluded. Results: Patients included in the study were 49 to 69 years old. All patients were treated as a case of hyponatremic encephalopathy in local hospitals. All patients had initial improvement followed by neurologic deterioration for which they were referred to our hospital. Possible etiologies of hyponatremia were recurrent vomiting and diuretic induced in two patients each and alcohol induced in one patient. Three out of five patients showed isolated extrapontine involvement on MRI. All patients showed improvement on dopaminergic drugs, whereas one patient had residual pseudobulbar symptoms which improved on follow-up. Conclusion: This series represents cases with clinical, etiopathogenic and radiologic spectrum of the ODS. ODS is a potentially treatable condition and rewarding results can be obtained by prompt diagnosis and management of associated secondary complications.
Keywords: Central pontine myelinolysis (CPM), extrapontine myelinolysis (EPM), hyponatremia, osmotic demyelination syndrome (ODS), parkinsonism
|How to cite this URL:|
Gupta S, Gupta S, Shroti A. Osmotic Demyelination Syndrome Presenting as Extrapontine Myelinolysis with or without Central Pontine Myelinolysis: Case Series of Five Cases and Review of Literature. MAMC J Med Sci [Epub ahead of print] [cited 2021 Dec 3]. Available from: https://www.mamcjms.in/preprintarticle.asp?id=330443
Key Message: Osmotic demyelination syndrome is a rare condition with varying clinical presentations. One should not be overtly enthusiastic when correcting hyponatremia and should follow recommended guidelines. Earlier considered to be fatal, proper supportive management can affect outcome in good way.
| Introduction|| |
Osmotic demyelination syndrome (ODS) represents a spectrum of movement disorders, psychiatric symptoms, and was first described in chronic alcoholics in 1959., Besides alcoholism, other reported associations include malnourishment, diuretics use, gastroenteritis, burns, malignancy, and posthepatic transplants.,, It is classically described following rapid correction of hyponatremia irrespective of underlying cause.
Patient most commonly presents with features of both pyramidal and extrapyramidal involvement varying from mask-like facies to spastic quadriparesis, pseudobulbar palsy, dystonia, and other movement disorders.
Earlier condition was described as fatal but with advanced imaging techniques, prompt diagnosis, and better intensive care facilities mortality rate has significantly reduced.,, Overall prognosis is not influenced by the degree of hyponatremia, as myelinolysis can follow a rise in serum sodium regardless of the cause or method of correction. Besides treating underlying etiology secondary complications warrants urgent attention as timely management can produce rewarding results. In this study, we focus on interesting clinical presentations, magnetic resonance imaging (MRI) findings, and overall outcome of patients with ODS along with brief review of literature of this rare entity.
| Method|| |
Ours is a tertiary care teaching institute in Southern Rajasthan. Data were collected retrospectively from in-hospital records of admitted patients between September 2018 and May 2020. Five cases diagnosed with ODS including both central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) were identified and clinical history and examination were duly recorded. The MRI brain images of included patients were analyzed from stored data. All other patients who had clinical features or imaging findings not consistent with diagnosis were excluded.
A 63-year-old male who was a known case of hypertension taking diuretic medications was admitted in a local hospital at periphery with 3 days history of clouding of consciousness. As peravailable records initial serum sodium was 93 mEq/L which was corrected with hypertonic saline (3% sodium chloride) to 132 mEq/L over a period of 24 hours. Following 3 days of initial improvement, he developed slowness of activities, aggressive behavior, emotional incontinence, impaired attention span, incoherent speech, and dysphagia following which he was referred to our hospital. On examination, he had mask-like facies, bradykinesia, bradyphrenia, slow horizontal saccade, broken pursuits, and cogwheel rigidity of all limbs. There was no history of alcohol intake, preceding fever, use of antipsychotics, sleep disturbance, or myoclonic jerks. Laboratory investigations showed increased creatine phosphokinase and lactate dehydrogenase levels, whereas other blood investigations and cerebrospinal fluid (CSF) analysis were normal [Table 1]. MRI brain showed T2/FLAIR hyperintensities in bilateral thalami, basal ganglia without pontine involvement [Figure 1]. Considering possibility of patient with ODS was started on dopaminergic drugs along with supportive treatment. Patient showed improvement in most of his symptoms except emotional incontinence at the time of discharge which also improved on 6 months follow-up.
|Figure 1 MRI brain showing T2/FLAIR hyperintensities in bilateral thalami, basal ganglia without pontine involvement.|
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A 49-year-old hypertensive male taking diuretic medications presented to us with progressive slowness of activities, increased response time, and reduced volume of speech for 10 days. Prior to admission in our institute, patient was treated in a local hospital for hyponatremia following bouts of recurrent vomiting. His serum sodium as documented in records was corrected from 106 to 130 mEq/L over a period of 24 hours. On examination, he was mute and apathetic, had slow saccades, and bilateral postural tremors were present. Laboratory investigations and CSF analysis were normal [Table 1]. MRI brain showed DWI/FLAIR hyperintense lesion involving bilateral basal ganglia without pontine involvement [Figure 2]. Patient had a history of excessive daytime sleepiness, night time snoring, and frequent dozing off episodes (Epworth sleepiness scale score 20). Arterial blood gas (ABG) was normal while polysomnography showed moderate grade obstructive sleep apnea. In view of ODS, he was started on dopaminergic agents following which he showed significant improvement. On follow-up at 4 months, patient had minimal residual symptoms.
|Figure 2 MRI brain showing DWI/FLAIR hyperintense lesion involving bilateral basal ganglia without pontine involvement.|
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A 52-year-old diabetic male with a history of daily alcohol intake for the last 7 to 8 years developed recurrent episodes of vomiting following an alcohol binge. Afterwards patient developed dizziness and altered sensorium. Subsequently, he was treated at local hospital as a case of hyponatremic encephalopathy. Patient had an initial mild improvement in sensorium but over next 5 days, he became lethargic, had reduced speech output, and had reduced oral intake following which he was referred to our institute. On examination, he had hypophonia, spastic quadriparesis with brisk reflexes, dysphagia, and bilateral postural and action tremor. There was no ataxia, opthalmoplegia, confabulation, focal weakness, and meningeal signs on examination. His routine laboratory investigations including ABG, urine ketone, and CSF analysis were normal [Table 1]. MRI brain showed FLAIR hyperintensity involving bilateral thalami, insular cortex, basal ganglia, and pons [Figure 3]. Patient was started on dopaminergic drugs and thiamine supplementation. On sixth day, patient showed improvement in sensorium, started accepting orally, and was discharged on dopaminergic medication. At 4 months follow-up, patient had no residual clinical features.
|Figure 3 MRI brain showing FLAIR hyperintensity involving bilateral thalami, insular cortex, basal ganglia, and pons.|
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A 65-year-old female patient had recurrent bouts of vomiting for 3 days, following which she developed seizures and altered sensorium. Patient was hospitalized in a local hospital and was treated with phenytoin sodium and was given sodium supplementation. There was no history of headache, rashes, chills or rigor, use of antipsychotics, diarrhea or prior seizure. On examination, she was in altered sensorium; there were no meningeal signs, ocular abnormalities, or focal deficits. On investigating further, her electroencephalogram did not revealed any epileptiform discharges and initial MRI was normal (images not available). Over next few days, she regained sensorium but subsequently developed extrapyramidal features such as slowness, tremors, and dysphagia following which she was referred to us. Follow-up MRI brain showed T2/FLAIR hyperintensities involving bilateral basal ganglia without any pontine involvement [Figure 4]. Considering possibility of ODS, she was started on dopaminergic supplementation and she showed improvement. At 3 months follow-up, patient had no residual deficits.
|Figure 4 MRI brain showing T2/FLAIR hyperintensities involving bilateral basal ganglia without any pontine involvement.|
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A 69-year-old hypertensive and diabetic male had recurrent vomiting for 5 days followed by altered sensorium. Patient was initially treated in a local hospital for hyponatremia (serum Na 124 mEq/L), and received sodium supplementation in unmeasured quantity. His clinical condition improved and was discharged from the primary hospital. Five days later, he started showing generalized slowness, lethargy, affective changes, and became mute. Later on, he developed tremulousness and bulbar symptoms following which he was hospitalized in our institute. On examination, he had spastic quadriparesis along with Parkinsonism More Details. Laboratory investigations including CSF analysis, urine ketone, and ABG were normal [Table 1]. MRI brain FLAIR images showed hyperintense lesion involving pons and bilateral basal ganglia suggestive of pontine and EPM [Figure 5]. Patient was started on dopaminergic drugs and trihexiphenidyl. During follow-up at 3 months, patient showed good improvement in his clinical features.
|Figure 5 MRI brain showing FLAIR images showed hyperintense lesion involving pons and bilateral basal ganglia suggestive of pontine and extrapontine myelinolysis.|
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| Discussion|| |
The ODS was first described in chronic alcoholics and malnourished as symmetrical butterfly-shaped patch of demyelination involving dorsal basis pontis. Rapid correction of hyponatremia is the most common etiology considered which was first described in 1976. Other potential etiologies include alcoholism, malnourishment, hypernatremia, prolonged period of altered serum osmolality, prolonged diuretic use, burns, and liver disorders.
Clinical presentation is usually biphasic. In the first phase, patients usually present in emergency room with altered sensorium related to hyponatremic encephalopathy following which they undergo hyponatremia correction and show initial clinical improvement. Few days later in the second phase, patients develop a neurologic syndrome due to ongoing myelinolysis., We observed similar pattern in all our patients who developed neurologic syndrome 3 to 10 days later following hyponatremia correction.
The ODS is a spectrum of clinical syndromes owing to differential involvement of neuraxis. Before classical symptoms of tetraparesis, pseudobulbar palsy, or locked in syndrome due to basis pontis involvement, patients may develop lethargy, affect changes, and even mutism which might delay diagnosis. Extrapontine involvement is reported in 10% of cases of CPM. In some cases, extrapontine involvement leads to various movement disorders such as parkinsonism, tremor, or dystonia,, which may even mask pyramidal features leading to diagnostic dilemma.
In this case series, cases 1, 2, and 4 had predominant extrapyramidal features, whereas cases 3 and 5, initially developed lethargic symptoms, dysphagia, and later on spastic quadriparesis. Cases 3 and 5 had a history of rapid hyponatremia correction along with MRI changes of pontine with extrapontine involvement, whereas isolated extrapontine involvement was observed in cases 1, 2, and 4. Underlying etiology of hyponatremia was different among the cases: in cases 1 and 2, it was diuretic induced, case 3 was alcoholic, whereas cases 4 and 5 had recurrent vomiting as predisposing factor [Table 2].
|Table 2 Patients’ demographics, clinical presentation, and possible ethology along with MRI features in summarized format|
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The CPM and EPM may coexist or present as isolated entity. They share common etio-pathogenesis, time course but have different clinical presentation and one may mask other depending on extent of myelinolysis.
Exact underlying pathogenesis and predilection of certain brain regions to myelinolysis in different subjects is still not completely understood. Pathologic studies suggest myelin damage with axonal and neuronal sparing; however, a recent study on CPM reported axonal damage. During hyponatremia, there is change in concentration of intracellular protein so rapid reversal can lead to protein destruction. Rapid correction of prolonged hyponatremia leads to cellular edema followed by demyelination.
In ODS, involvement of pons with or without extrapontine structures may be observed depending on extent of demyelination and vulnerability of brain structure. In CPM and EPM, bilateral symmetrical involvement of central basis pontis and basal ganglia and thalamus, respectively, is observed.,,
The MRI is imaging modality of choice; however, initial MRI may be normal as in one of our case (case 4) despite profound neurologic deficits. It may take upto 2 weeks for changes to appear in MRI initially. Follow-up MRI may show resolution of MRI changes despite persistent neurologic symptoms, as no consistent correlation has been found between radiologic resolution and clinical improvement.
Although characteristic T2/FLAIR pontine involvement with peripheral sparing with bilateral symmetric basal ganglia involvement is suggestive of ODS, isolated extrapontine involvement may lead to diagnostic difficulty.,
Wide differentials of bilateral basal ganglia or thalami involvement include hypoxic-ischemic injury, Wilson disease, carbon monoxide poisoning, and Leigh disease. Infective pathologies, deep venous thrombosis, and mitochondrial cytopathies can also present with patchy signal abnormalities.
Treatment is mainly supportive. Earlier considered to be a fatal condition with devastating complications in survivors, recent literature suggest improved outcomes and longer survival., Although there is no specific treatment for myelinolysis, potential role of various treatment modalities such as plasma exchange, intravenous immunoglobulin, steroids, thyrotropin-releasing hormone, and even reinstitution of hyponatremia have been suggested.
Beneficial role of dopaminergic drugs and antidystonic drugs in treatment of extrapyramidal features in still controversial., Recovery following institution of dopaminergic theory may be attributed to natural course of disease process or amelioration of transient dysfunction of nigrostriatal pathway. Also increased synaptic plasticity and resolution of vasogenic edema might be a plausible explanation for recovery on follow-up.
Besides pharmacologic management behavioral therapies can produce rewarding outcome, so a multidisciplinary approach involving neurologists, psychiatrists, clinical psychologists, physiotherapists, and speech therapists should be used.
Due to advanced imaging and management modalities in recent times, favorable outcomes have been reported. Prevention of secondary complications affect overall prognosis. In addition, overall outcome does not depend on degree of hyponatremia or severity of neurologic illness.
So to summarize, in this case series of five patients, three had isolated extrapontine, whereas two had pontine along with extrapontine involvement. Initial MRI was normal in one case, whereas remaining four showed initial radiologic changes. Three patients had predominant extrapyramidal features, whereas two had predominant pyramidal tract involvement. Documentation of correcting hyponatremia in local hospitals was available in three patients. All patients showed initial improvement and then shifted to our institute on worsening of neurologic status. All patients showed recovery on dopaminergic drugs, whereas one patient developed psychotic symptoms which gradually recovered.
| Conclusion|| |
The ODS although rare is a potentially treatable condition with outcome largely depending on early diagnosis and management. Often missed on initial workup, this condition needs a high index of clinical suspicion especially in presence of some underlying risk factors as timely management can produce rewarding results.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]