Centropontine myelinolysis after rapid correction of hyponatremia: a case report

¹Resuscitation Department, Ibn Zohr University and Regional Hospital Center Hassan II Agadir, Agadir, Morocco, ²Radiology Department, Ibn Zohr University and Regional Hospital Center Hassan II Agadir, Agadir, Morocco, ³Nephrology Department, Ibn Zohr University and Regional Hospital Center Hassan II Agadir, Agadir, Morocco

^&Corresponding author
Abderrahim Wakrim, Resuscitation Department, Ibn Zohr University and Regional Hospital Center Hassan II Agadir, Agadir, Morocco

Introduction    

Centro-pontine myelinolysis (CPM) and extra-pontine myelinolysis (EPM), grouped together in osmotic demyelination syndrome (ODS), is a rare pathology characterized by the destruction of the myelin sheath. From a pathophysiological point of view, this syndrome corresponds to the rapid correction of an osmotic disorder in fragile brain cells. Numerous predisposing factors have been described, such as chronic alcoholism, undernutrition, psychogenic polydipsia, and metabolic disorders such as hypokalemia, which may play a favourable role [1]. Rapid correction of hyponatremia remains the typical cause of this syndrome [2]. We report the case of a patient with hyperemesis gravidarum complicated by renal failure, in whom correction of hyponatremia with 3% hypertonic saline resulted in CPM.

Patient and observation     

Patient information: we report the case of a 19-year-old female patient admitted to the intensive care unit for the management of consciousness disorders that progressively set in over 4 days. One week earlier, the patient had been admitted to the nephrology department for renal failure due to hyperemesis gravidum complicated by miscarriage at 12 weeks' amenorrhea. Past medical history, and drug and family histories were not significant.

Clinical findings: on admission, the patient was unconscious, GCS 7/15, tetraparesis with generalized muscular hypotonia, and was placed on mechanical ventilation.

Timeline of current episode: the condition started at home with a miscarriage on 19/11/2022. The patient developed hypermesis gravidarum for 4 days before being admitted to the nephrology department on 24/11/2022 for renal failure [creatinine: 455.26 umol/l, urea: 354 mg/dl] associated with electrolyte disorders [hyponatremia at 120 mm/l, hypokalemia at 2.6 mmol/l]. During her hospitalization in nephrology, the patient benefited from rehydration with isotonic saline combined with correction of hyponatremia with hypertonic saline 3%, and increased basic potassium intake. Correction of such anomalies started on 28/12/2022. The neurological deterioration was accompanied by a rise in Natremia from 120 mmol/L to 129 mmol/L on day 1, then to 140 mmol/L on day 2, before reaching 160 mmol/L on day 3, with an increase of 41.3 mmol in 72 hours, prompting her transfer to the intensive care unit when became completely unconscious on 02/01/2023. Upon admission, the patient was placed on mechanical ventilation. Cerebral CT scan and lumbar puncture were without abnormality (CSF: WBC <3/mm³, Proteinorachy and Glycorachy normal), and given the suspicion of Gayet Wernicke encephalopathy, a vitamin B1 assay was ordered, showing a low level of 40 nmol/l [normal value: 83-245 nmol/l]. Given the lack of neurological improvement after vitamin supplementation and correction of hypernatremia and renal insufficiency, magnetic resonance imaging (MRI) was performed, showing centropontine myelinolysis.

Diagnostic assessment: magnetic resonance imaging (MRI) was performed, showing centropontine myelinolysis (Figure 1, Figure 2, Figure 3).

Therapeutic intervention: subsequent management focused on neuro-resuscitation, preventing secondary attacks of systemic origin and correcting hydroelectrolytic, metabolic and vitamin disorders.

Follow-up and outcomes: during her stay, the patient was tracheostomized on the 8^th day of hospitalization and weaned from the ventilator on the 33^rd day, to become autonomous on the 50^th day with muscle strength 3/5 on all four limbs. Progression at 3 months was marked by complete recovery of muscle strength and coordination in the 2 upper limbs, and the possibility of walking with support, resulting in complete and total autonomy for the patient.

Patient perspective: upon gaining consciousness, the patient and the patient's family were pleased about the hospital care and the interventions. The patient´s family were surprised by the evolution as they initially lost hope in her survival.

Informed consent: an informed written consent was obtained from the patient to publish this work.

Discussion     

Centropontine myelinolysis is a rare non-inflammatory demyelinating condition. Pearce JMS described the changing concepts and metabolic etiology of CPM since it’s first description [3]. It mainly affects the annular protuberance, known as centropontine myelinolysis, but can also affect extrapontine fibers in the cerebellum and thalamus, known as extrapontine myelinolysis [3]. The true incidence of this pathology remains unknown to this day [4]. Initially described in malnourished alcoholic patients [5] but recent studies have shown its occurrence in electrolyte disorders, particularly hyponatremia, and its rapid correction.

From a pathophysiological point of view, during a chronic osmotic disorder, brain cells adapt their organic osmolyte content to compensate for osmotic changes. Rapid correction of this disorder exposes the cells, and in particular the oligodendrocytes, to a massive influx of osmoles, leading to shrinkage and impairment of their function, and thus to symmetrical destruction of myelin (demyelination) [6]. Combined with reduced NaK-ATPase concentrations in endothelial cell membranes in the setting of hypokalemia, this may render the cells vulnerable to osmolarity damage secondary to the rapid rise in serum sodium [1]. Among the risk factors described in the literature, chronic alcoholism, malnutrition, hyponatremia, hypokalemia, and inappropriate nutrition remain the best understood and most elucidated from a pathophysiological point of view [7]. Its association with other pathologies, notably hyperemesis gravidarum, as in the case of our patient, has been reported in the literature [8,9].

The diagnosis of Centro-pontine myelinolysis (CPM) is based on the clinical history, which combines risk factors with a variety of clinical symptoms ranging from paraparesis to paraplegia, Locked-in syndrome and even death. Biological tests are not specific, but can be used to suspect the diagnosis when there is a sudden and rapid change in plasma tonicity, in particular a rapid correction of hyponatremia. After eliminating differential diagnoses, such as central nervous system infection by lumbar puncture, the diagnosis is confirmed by cerebral MRI [7]. Cerebral MRI is the radiological examination of choice, showing a hypersignal area on T2- and FLAIR-weighted sequences, hyposignal on T1-weighted sequences, with lesions appearing only late in the course of 10-15 days. CSF studies are often normal, as in our patient's case, as is a non-specific EEG [3,9]. Treatment is essentially preventive and is based on reasonable and progressive correction of any hyponatremia at a rate not exceeding 0.5 mmol/l/h., with no validated curative treatment to date [9].

The prognosis was once considered poor and universally fatal. However, since the pathology was first described, the prognosis has steadily improved and, according to one study, the patient mortality rate has fallen to just 7% since 1990 [7]. In a multicenter study carried out in intensive care units, no prognostic factors were identified, and surprisingly, morbidity and mortality were not associated with neurological severity, general complications due to neurological severity, or other factors that may increase neurological severity (hypoxia, sepsis, etc.) [10]. There is also a growing awareness of this potential complication linked to electrolyte imbalances, particularly with regard to sodium. Improved access to intensive care and early intubation in the event of respiratory complications, including arrest, may also be a key factor in improving prognosis, with less severe residual neurological sequelae.

Conclusion     

Centro-pontine myelinolysis (CPM) is a rare, little-known pathology with an often unfavorable evolution. The approach is essentially preventive, with simultaneous correction of electrolyte disorders such as hyponatremia and hypokalemia, but with caution. This case may well be seen as an appropriate example to reinforce the warning to physicians about the inappropriate and excessive use of hypertonic saline to avoid rapid changes in serum osmolarity, which can have dramatic and sometimes irreversible consequences.

Competing interests     

The authors declare no competing of interests.

Authors' contributions     

All the authors have read and agreed to the final manuscript.

Figures     

Figure 1: cerebral MRI T1 sequence in sagittal section without contrast injection (A); and T1 sagittal and axial sequence (B and C) with injection showing a central pontine lesion (green arrow) with respect for the periphery, in T1 hyposignal in axial section, with discrete contrast in favor of the acute phase of osmotic demyelination syndrome (ODS)

Figure 2: cerebral MRI T2 sequence (A) and FLAIR sequence (B) showing a central pontine lesion (green arrow) with respect for the periphery, in hyper signal

Figure 3: brain MRI diffusion sequence (A) showing a central pontine lesion with respect for the periphery in hyper signal (green arrow) with focal drop in ADC (B) (red arrow) without signal gap at SWI sequence (C) in favor of the acute phase of osmotic demyelination syndrome

References