Delayed Osmotic Demyelination Syndrome Treated Successfully with Therapeutic Plasma Exchange: A Case Report

Aarthee Asokan¹ https://orcid.org/0000-0002-1633-7906, Dhanaraj Mathuram² https://orcid.org/0000-0002-8721-8197, Mark A Augustus³ https://orcid.org/0000-0002-2512-3790

^1-3Department of Neurology, Apollo Main Hospital, Chennai, Tamil Nadu, India

Corresponding Author: Aarthee Asokan, Department of Neurology, Apollo Main Hospital, Chennai, Tamil Nadu, India, Phone: +91 8072653068, e-mail: aartheemed@gmail.com

Received on: 10 June 2023; Accepted on: 02 July 2023; Published on: 18 August 2023

ABSTRACT

Osmotic demyelination syndrome (ODS) is an uncommon neurological disorder, generally following rapid correction of hyponatremia resulting in demyelination of the white matter of the pons and certain extrapontine regions. The neurological symptomatology can vary from mild confusion to severe dense global paralysis, coma, or death. Once ODS is established, there is no proven treatment. Several experimental therapies, such as reinduction of hyponatremia, intravenous immunoglobulin (IVIG), plasma exchange, and steroids, have been tried with variable success. In this case report, we describe a case of ODS with global paralysis that responded well to plasma exchange therapy despite a full month has passed since the onset of symptoms. This is probably one of the first few cases reported from this part of the country.

How to cite this article: Asokan A, Mathuram D, Augustus MA. Delayed Osmotic Demyelination Syndrome Treated Successfully with Therapeutic Plasma Exchange: A Case Report. Indian J Crit Care Case Rep 2023;2(4):91–93.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

Keywords: Case report, Central pontine myelinolysis, Extra pontine myelinolysis, Osmotic demyelination syndrome

HIGHLIGHTS

The unique features in the present patient include the following—even though plasma exchange was initiated 1 month after the onset of symptoms; the patient recovered well despite having dense weakness in all four limbs, bulbar muscles, as well as involuntary movements of the lips. This emphasizes that delayed plasma exchange could still be beneficial to patients. This patient is probably one of the first few cases of ODS to be successfully treated with plasma exchange from this part of the country.

INTRODUCTION

Osmotic demyelination syndrome (ODS) comprises central pontine and extrapontine myelinolysis either occurring alone or in combination following rapid correction of hyponatremia. It is commonly seen among alcoholics and liver transplant patients.¹^-³ The symptoms generally vary from mild weakness to devastating dense quadriplegia presenting with bulbar involvement. As of now, supportive therapy is used to manage established ODS because there is no proven treatment for the condition.⁴ Several modalities of treatment, such as reinduction of hyponatremia immediately after the diagnosis of ODS, intravenous immunoglobulins (IVIGs), steroids, and plasma exchange, have been tried.³^-⁵ Recently, there have been few reports of successful treatment of ODS with therapeutic plasma exchange.⁶^,⁷ In this paper, we report a case of ODS presenting as locked-in syndrome with extrapyramidal features, who entirely recovers following therapeutic plasma exchange performed one month after the onset of symptoms.

CASE DESCRIPTION

A 49-year-old male, known diabetic and hypertensive, presented with a history of one attack of generalized tonic-clonic seizures for which he was admitted to a local hospital and treated for the same. On the 3rd day of admission at the local hospital, he developed a fever with altered sensorium. He was suspected of having meningoencephalitis and was started on IV antibiotics and antivirals. Relevant investigations, including magnetic resonance imaging (MRI) brain and cerebrospinal fluid studies, were done, and were reported normal. He was also incidentally found to have hyponatremia with a serum sodium level of 117 mEq/L. It was corrected to 145 mEq/L over a period of 48 hours. During this time period, he developed severe weakness in all four limbs, including difficulty in swallowing and breathing, and hence was intubated and subsequently tracheostomized. As his clinical status continued to worsen, the doctors at the local hospital initiated IVIG along with IV steroids in suspicion of autoimmune encephalitis. However, further details regarding the autoimmune encephalitis workup at the local hospital were unavailable. As there was no improvement for almost a period of 1 month, he was referred to our hospital for further management.

On admission (15 June 2022), he was conscious and had purposeless spontaneous movements of his eyeball in all directions. All four limbs were severely weak, with a power of grade zero. The muscles of the jaw, face, palate, trunk, and neck were also weak (Video 1). The tone was relatively normal. Deep tendon reflexes were preserved. Plantar reflexes were mute bilaterally. Tremors of tongue, lips, and eyelids were present. There were no signs of meningeal irritation. Clinical diagnosis of ODS secondary to rapid correction of hyponatremia, probably involving pons and basal ganglia, was suspected.

Magnetic resonance imaging (MRI) brain done on the same day showed T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensities in the pons and basal ganglia features suggestive of ODS (Fig. 1). The patient had already received IVIG and IV steroids in the local hospital with no benefit. Hence considering the delayed presentation, the severity of the neurological status of therapeutic plasma exchange opted was considered. After counseling the family regarding the prognosis of ODS, and the role of therapeutic plasma exchange, it was started on 16^th June 2022. Altogether, five cycles of plasma exchange were done on alternate days. In each cycle, a volume of 3500 mL of plasma was exchanged, totaling 17500 mL over 10 days.

Fig. 1: Magnetic resonance imaging (MRI) brain FLAIR—showing hyperintensities in central pons and basal ganglia suggestive of ODS

Following each exchange, he showed subtle motor improvement in all four limbs (Video 2). Over a period of 1 month and 15 days, muscle power in all four limbs improved significantly; the tracheotomy stoma was closed, Ryles tube and catheter were removed. At discharge, the patient was able to walk with support. He was completely normal at his follow-up 15 days later (Video 3).

DISCUSSION

Osmotic demyelination syndrome (ODS) is a well-known complication occurring after rapid correction of hyponatremia.¹^,³ Additional risk factors for it include anorexia nervosa, severe burns, hyperemesis gravidarum, chronic liver disease, alcoholism, and liver transplantation.¹ The symptoms of central pontine myelinolysis generally vary from mild weakness, memory disturbances, delirium, frontal dysfunction characterized by memory, speech disturbances, and ocular and papillary involvement to devastating dense quadriplegia presenting with bulbar involvement—“locked-in syndrome.” The symptoms of extrapyramidal pontine myelinolysis include tremor, dystonia, opsoclonus, gait disturbances, myoclonus, ataxia, rigor, and cerebellar signs.³ Other general and neurobehavioral symptoms include seizures, apathy, lethargy, and dementia.³

The exact mechanism of ODS is still unclear. It is believed that following chronic hyponatremia, the brain cells develop an adaptive mechanism characterized by active efflux of osmolytes from the intracellular into the extracellular compartment in order to maintain osmotic equilibrium.¹ Once the brain cells have developed this adaptation, a rapid rise in the extracellular sodium secondary to rapid correction, a state of osmotic disequilibrium sets in. This is because the osmolytes in the extracellular compartment cannot move freely and rapidly back into the intracellular compartment.⁵^,⁶ This happens especially in certain parts of the brain, such as pons, since the white matter is packed tightly together, resulting in dehydration, shrinkage of the neuronal cells, breakdown of the blood-brain barrier as well as the release of myelinotoxic substances, which produces ODS.⁵^,⁶ Histopathology of ODS is characterized by noninflammatory demyelination typically with preservation of axons and neurons.⁷

CONCLUSION

There are no proven treatment options for ODS. ODS has always been a disease with significant morbidity and mortality; plasma exchange could be a life-saving procedure. As described in this patient, delayed treatment was also extremely beneficial. Plasma exchange could hence be an effective treatment option for severe and even delayed forms of ODS. Large-scale studies are needed to prove the efficacy and practicality of therapeutic plasma exchange in patients with ODS.

The diagnosis of ODS is based on relevant clinical history with radiological substantiation. MRI findings are suggestive of ODS characterized by demyelinating lesions visualized as T2 hyperintensities and T1 hypointensities. Once ODS is established, to date, there is no proven treatment except supportive treatment. When the symptoms are mild to moderate, most patients recover with the above treatment.¹^,² However, when severe, as in this patient, there is no specific treatment. Several experimental therapies have been tried for the management of the same, including (1) reinduction of hyponatremia (which must be done immediately after the onset of symptoms; (2) IVIGs; (3) IV steroids; and (4) plasma exchange.⁴^,⁷ However none of them have been proven statistically. Recently a few authors have reported successful use of plasma exchange among such patients presenting within the first 2 weeks of the onset of symptoms.

Bibl et al., in 1999, used therapeutic plasma exchange successfully to treat three young female patients with central pontinemyelinosis.⁴ Similarly, Wijesundara et al., from Sri Lanka, reviewed a total of 16 patients with extra pontine myelinolysis.⁷ Out of the 16 patients, 10 patients received plasma exchange alone, four patients received a combination of plasma exchange followed by IVIG, and two patients received triple therapy with plasma exchange, IVIG, and IV steroids. Among the 16 patients, eight had total recovery from the motor weakness, five were able to walk with assistance, one patient walked with support, and two patients had a suboptimal response.⁷ The study concluded that plasma exchange was very effective in patients with ODS and hence recommended it to be a standard treatment.⁷

The principle behind therapeutic plasma exchange is that it removes myelinotoxic substances, which are released as a result of cellular damage following osmotic disequilibrium.⁷ It has also been postulated that ODS also has an inflammatory etiology, and hence the removal of these inflammatory substances helps to improve the deficit.¹^,²

SUPPLEMENTARY MATERIAL

Supplementary material has been provided on the website www.ijccr.org

ORCID

Aarthee Asokan https://orcid.org/0000-0002-1633-7906

Dhanaraj Mathuram https://orcid.org/0000-0002-8721-8197

Mark A Augustus https://orcid.org/0000-0002-2512-3790

REFERENCES

1. Adams RD, Victor M, Mancall EL. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. AMA Arch of Neurol Psychiatry 1959;81(2):154–172. DOI: 10.1001/archneurpsyc.1959.02340140020004

2. Chang KY, Lee IH, Kim GJ, et al. Plasma exchange successfully treats central pontine myelinolysis after acute hypernatremia from intravenous sodium bicarbonate therapy. BMC Nephrol 2014;15:56. DOI: 10.1186/1471-2369-15-56

3. Lambeck J, Hieber M, Dreßing A, et al. Central pontine myelinosis and osmotic demyelination syndrome. Dtsch Arztebl Int 2019;116(35-36):600–606. DOI: 10.3238/arztebl.2019.0600

4. Bibl D, Lampl C, Gabriel C, et al. Treatment of central pontine myelinolysis with therapeutic plasmapheresis. Lancet 1999;353(9159):1155. DOI: 10.1016/S0140-6736(99)01145-9

5. Adler S, Verbalis JG, Meyers S, et al. Changes in cerebral blood flow and distribution associated with acute increases in plasma sodium and osmolality of chronic hyponatremic rats. Exp Neurol 2000;163(1):63–71. DOI: 10.1006/exnr.2000.7376

6. George JC, Zafar W, Bucaloiu ID, et al. Risk factors and outcomes of rapid correction of severe hyponatremia. Clin J Am Soc Nephrol 2018;13(7):984–992. DOI: 10.2215/CJN.13061117

7. Wijesundara D, Senanayake B. Plasmapheresis for extrapontine myelinolysis: a case series and a literature review. Case Rep Neurol 2022;14(1):72–81. DOI: 10.1159/000521814

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