Atypical forms of the osmotic demyelination syndrome
Upcoming SlideShare
Loading in...5
×
 

Atypical forms of the osmotic demyelination syndrome

on

  • 471 views

José L. Ruiz-Sandoval, Erwin Chiquete, ...

José L. Ruiz-Sandoval, Erwin Chiquete,
Lucía E. Álvarez-Palazuelos, Miguel
A. Andrade-Ramos & Luis R. Rodríguez-
Rubio

Osmotic demyelination syndrome (ODS) is the
damage over the central nervous system caused by several
electrolytes, metabolic and toxic disorders. We aimed to
describe cases of unusual forms of ODS. In a 9-year period,
25 consecutive patients with ODS (15 men; mean age
42 years) were registered in our referral institution, among
them, four (16 %) with atypical neuroimaging findings
were abstracted for this communication. None of them
presented cardiorespiratory arrest, head trauma, seizures,
neuromyelitis optica spectrum or contact with toxic
chemicals. Case 1 was a 33-year-old alcoholic man without
hypertension or electrolyte imbalance, who presented a
classic central pontine myelinolysis (CPM) and a hemorrhage
within the pons. Case 2 was a 34-year-old alcoholic
man with hypoglycemia and hyponatremia who presented
CPM and diffuse bihemispheric extrapontine myelinolysis
(EPM) after correction of serum sodium. Case 3 was a
52-year-old woman with mild hypokalemia and hyponatremia
(inadequately corrected), who presented a peduncular
and cerebellar EPM. Case 4 was a 67-year-old
woman who had a suicidal attempt with antidepressants
and carbamazepine without impaired consciousness, who
complicated with mild hyponatremia associated with a
classical CPM and a spinal cord EPM. Case 2 died and the
rest remained with variable neurological impairments at
last follow-up visit. With modern neuroimaging, the
so-called atypical forms of ODS may not be as rare as
previously thought; however, they could have a more
adverse outcome than the classical ODS.

Statistics

Views

Total Views
471
Views on SlideShare
467
Embed Views
4

Actions

Likes
0
Downloads
6
Comments
0

1 Embed 4

http://www.slideee.com 4

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Atypical forms of the osmotic demyelination syndrome Atypical forms of the osmotic demyelination syndrome Document Transcript

  • Atypical forms of the osmotic demyelination syndrome José L. Ruiz-Sandoval, Erwin Chiquete, Lucía E. Álvarez-Palazuelos, Miguel A. Andrade-Ramos & Luis R. RodríguezRubio Acta Neurologica Belgica ISSN 0300-9009 Acta Neurol Belg DOI 10.1007/s13760-012-0110-5 1 23
  • Your article is protected by copyright and all rights are held exclusively by Belgian Neurological Society. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your work, please use the accepted author’s version for posting to your own website or your institution’s repository. You may further deposit the accepted author’s version on a funder’s repository at a funder’s request, provided it is not made publicly available until 12 months after publication. 1 23
  • Author's personal copy Acta Neurol Belg DOI 10.1007/s13760-012-0110-5 ORIGINAL ARTICLE Atypical forms of the osmotic demyelination syndrome ´ ´ ´ Jose L. Ruiz-Sandoval • Erwin Chiquete • Lucıa E. Alvarez-Palazuelos • Luis R. Rodrıguez-Rubio ´ Miguel A. Andrade-Ramos • Received: 27 March 2012 / Accepted: 22 June 2012 Ó Belgian Neurological Society 2012 Abstract Osmotic demyelination syndrome (ODS) is the damage over the central nervous system caused by several electrolytes, metabolic and toxic disorders. We aimed to describe cases of unusual forms of ODS. In a 9-year period, 25 consecutive patients with ODS (15 men; mean age 42 years) were registered in our referral institution, among them, four (16 %) with atypical neuroimaging findings were abstracted for this communication. None of them presented cardiorespiratory arrest, head trauma, seizures, neuromyelitis optica spectrum or contact with toxic chemicals. Case 1 was a 33-year-old alcoholic man without hypertension or electrolyte imbalance, who presented a classic central pontine myelinolysis (CPM) and a hemorrhage within the pons. Case 2 was a 34-year-old alcoholic man with hypoglycemia and hyponatremia who presented CPM and diffuse bihemispheric extrapontine myelinolysis (EPM) after correction of serum sodium. Case 3 was a 52-year-old woman with mild hypokalemia and hyponatremia (inadequately corrected), who presented a peduncular and cerebellar EPM. Case 4 was a 67-year-old woman who had a suicidal attempt with antidepressants and carbamazepine without impaired consciousness, who complicated with mild hyponatremia associated with a classical CPM and a spinal cord EPM. Case 2 died and the rest remained with variable neurological impairments at last follow-up visit. With modern neuroimaging, the so-called atypical forms of ODS may not be as rare as J. L. Ruiz-Sandoval (&) Á E. Chiquete Á ´ L. E. Alvarez-Palazuelos Á M. A. Andrade-Ramos Á ´ L. R. Rodrıguez-Rubio ´ ´ Servicio de Neurologıa y Neurocirugıa, Hospital Civil de Guadalajara ‘‘Fray Antonio Alcalde’’, Hospital 278, Guadalajara, Jalisco 44280, Mexico e-mail: jorulej-1nj@prodigy.net.mx previously thought; however, they could have a more adverse outcome than the classical ODS. Keywords Central pontine myelinolysis Á Extrapontine myelinolysis Á Neuroimaging Á Osmotic demyelination Á Osmotic myelinolysis Introduction Osmotic demyelination syndrome (ODS) is the term that better describes the damage that over the central nervous system cause multiple electrolytes, metabolic and toxic disorders. Since the original description in 1959 by Adams et al. [1], and later in 1979 by Wright et al. [2], central pontine (CPM) and extrapontine myelinolysis (EPM), respectively, have been reported as the common forms of ODS. Rapid correction of hyponatremia was the first recognized risk factor, but it is currently known that ODS can occur even with an ‘‘adequate’’ correction of hyponatremia [3] and in the absence of serum sodium imbalances [4, 5]. Histopathologically, CPM is an axonal-sparing noninflammatory degeneration of oligodendrocytes localized in the basis pontis [5]. The lesions are typically symmetrical and can spread to other anatomical areas such as cerebellum and supratentorial structures. This spread represents the main concept of EPM [4, 5]. ODS can be suspected on CT, but MRI is the technique of choice that suggests a premortem diagnosis of myelinolysis; lesions with hypointense signals are seen on T1 and they are hyperintense on T2-weighted MRI. Since ODS is not an inflammatory process, the lesions are classically non-enhancing after gadolinium administration [4, 6]. These neuroimaging characteristics correspond pretty well with those observed in autopsy investigations [4]. Thus, 123
  • Author's personal copy Acta Neurol Belg MRI has increased the recognition of atypical forms of this entity in the context of known risk factors, typical neuroimaging as well as the clinical and radiological presentation. Herein, we describe four patients with unusual radiological presentations of ODS. Methods In a 9-year period, 25 consecutive patients with ODS (15 men, mean age 42 years) were registered, of whom four (16 %) with atypical neuroimaging findings were abstracted for this analysis (Fig. 1). All patients were assessed with 1.5 Tesla MRI. All patients were alert during the initial clinical evaluation. We excluded cases associated with cardiorespiratory arrest, head trauma, seizures, the neuromyelitis optica spectrum (i.e., positivity to NMOIgG/anti-AQP4) or contact with toxic chemicals, given their neuroimaging appearance similar to that of ODS [6]. Results Hemorrhagic CPM (Fig. 1a) A 33-year-old alcoholic man, without history of hypertension, was admitted to our center due to acute bilateral lower-limb paresis that evolved to quadriparesis in 48 h, accompanied with vomiting, diplopia and dysphagia. At hospital arrival the patient was alert, with dysarthric speech, unable to abduct both eyes, with moderate bilateral facial paresis, with dysphagia, with quadriparesis and bilateral Babinski sign. No electrolyte, platelet count or coagulation abnormalities were observed. A non-contrast head CT scan showed an atypical patchy and confluent hyperdensity within the tegmental pons without changes on the contrast phase. All these findings were compatible with a pontine hemorrhage. Six days later a brain T2-weighted MRI showed a heterogeneous lesion with a diffuse hyperintense signal and a central hypointensity suggestive of hemosiderin deposits within the pons. An angiographic study was negative for intracranial vascular malformations. Medical support treatment and rehabilitation was offered. At 2-year follow-up, the patient presents occasional dizziness and has brisk reflexes without paresis. CPM and diffuse bihemispheric EPM (Fig. 1b) A 34-year-old alcoholic man was admitted to the Emergency Department with altered mental status, hypoglycemia (58 mg/dl, normal 70–100 mg/dl) and hyponatremia (122 mmol/l, normal 135–146 mmol/l), which was inadequately corrected in the following hours (4 mmol/l/h). An 123 initial head CT scan showed collapsed ventricles and sulcal effacement. No cardiorespiratory arrest or hypoxia events were identified at any moment of the pre-hospital history or during the hospital stay. However, due to worsening of the neurological status (stupor), a second CT scan was performed 72 h after hospital presentation. The new imaging showed hypodense basal ganglia and a diffuse hyperdense laminar image at the cortical-subcortical junction in the non-contrast CT phase and after contrast administration. A T2-FLAIR brain MRI demonstrated diffuse brainstem and bihemispheric abnormalities consistent with a dramatic global myelinolysis. No gadolinium enhancement was observed. The patient was discharged in vegetative state and died at home 2 weeks later. Cerebellar peduncular EPM (Fig. 1c) A 52-year-old woman with a history of diabetes, hypertension and chronic antidepressants use was admitted to our institution with a 5-day history of generalized mild weakness, vomiting and difficult speech. On admission, hyponatremia (119 mmol/l) and hypokalemia (2.9 mmol/l, normal 3.5–5.0 mmol/l) were detected and inadequately corrected (6 mmol/l/h). On the following 48 h, the neurological status worsened and mechanical ventilation was installed. A brain T2-weighted MRI evidenced diffuse peduncular hyperintense signals involving the cerebellum, consisting with the rare cerebellar ODS. The patient was discharged 3 weeks later after receiving gastrostomy and feeding tube placement, with severe dysphagia, dysarthric speech, gait disturbance, postural instability, moderate ataxia of the four limbs and mild tremor and dysdiadochokinesis in the upper limbs. CPM and spinal EPM (Fig. 1d) A 67-year-old woman with history of diabetes, diabetic neuropathy and depression was managed in another hospital for a suicidal attempt (with antidepressants and carbamazepine) complicating with a mild hyponatremia (130 mmol/l), for which no information on management could be obtained. After 1 week of hospital stay she was discharged with somnolence, dysarthria, dysphagia and quadriparesis. Asking for a second opinion she was admitted to our hospital with pseudobulbar affect, horizontal nistagmus, dysarthria, spastic quadriparesis, bilateral Babinski sign and urinary incontinence, without a sensory level. A cranio-spinal T2-weighted MRI showed a typical pontine hyperintensity compatible with a classic central myelinolysis and a longitudinal lesion from C2 to T7 spinal cord segments, suggesting a common etiology. CSF laboratory tests showed a non-inflammatory fluid (proteins
  • Author's personal copy Acta Neurol Belg Fig. 1 Brain imaging studies in the four cases presented. a Hemorrhagic central pontine myelinolysis. b Central pontine and diffuse hemispheric extrapontine myelinolysis. c Peduncular and cerebellar myelinolysis. d Pontine and spinal myelinolysis 37 mg/dl, glucose 48 mg/dl, leukocytes 0) and the serum was negative for NMO-IgG/anti-AQP4, antinuclear, SSA or SSB antibodies. Routine CSF stains and cultures were negative for microbial growth and no viral genome was amplified by polymerase chain reaction. The patient was discharged with mild quadriparesis, dysarthric speech and dysphagia. She was lost to follow-up after 6 months without any clinical recurrence. 123
  • Author's personal copy Acta Neurol Belg Discussion ODS was first described as a distinct pathological entity identified by autopsy; however, a reliable premortem diagnosis is now possible on the basis of MRI techniques [7, 8]. Here, we report four patients with infrequent radiological forms of ODS who presented well-known risk factors. Indeed, several toxic, infectious and inflammatory disturbances can present similar neuroimaging findings to those described in this case series. Nevertheless, we excluded other causes of the clinical and radiological characteristics of our patients. In our opinion, no other common risk factors, blood tests, CSF analyses or brain and spine MRI/CT scanning could demonstrate alternative etiologies. Hemorrhagic CPM Hyperdense lesions on CT have been identified within hypodensities compatible with ODS. Calakos et al. [7] reported a case of cortical–subcortical EPM, with lesions described as ‘‘multifocal punctate hemorrhages’’. In classic non-hemorrhagic CPM, hyperdense images on CT can be seen only after contrast administration, suggesting a blood– brain barrier disruption or myelin degradation with modification of the lipid/protein ratio [8]. Rouanet et al. reported a patient with CPM who showed a hypointense signal in T2-weighted MRI over the classical hyperintensity consistent with pontine demyelination. They did not considered this finding as a pontine hemorrhage, since a noncontrast head CT did not show a hyperdense lesion [8]. In our case, the hyperdensity was evident in the non-contrast CT, a finding clearly compatible with a parenchymal hematoma. We hypothesize that the same osmotic injury that causes the myelinolytic process can also generate an endothelial damage that could lead to vascular disruption and hemorrhage, either as primary or collateral osmotic injury, in a susceptible patient [9]. Diffuse supratentorial CPM/EPM Although EPM in the basal ganglia, periventricular white matter and cortico-subcortical junction have been described as forms of ODS since 1988, these locations are unusual and scarcely reported [2, 7, 10–12]. Cortical laminar lesions have been described in ODS with variable pathological findings that include cortical laminar necrosis [10–13], laminar demyelination with gliosis, or both [2, 7]. In our patient, the burden of chronic alcoholism, other inherent nutritional deficiencies and the metabolic and electrolyte disturbances documented at hospital admittance could explain the diffuse demyelination. We completely excluded in this patient a state of hypoperfusion or hypoxia, which 123 may present similar neuroimaging findings compared with those seen after the osmotic injury. Evidence exists on a down-regulation of genes involved in myelin synthesis and maintenance, associated with predisposition to alcohol abuse [14]. Thus, it appears that alcoholism is a vulnerable state that predisposes to ODS. Cerebellar EPM ODS presenting with ataxia is very rare [5], and cerebellar myelinolysis with or without CPM has been reported scarcely in the scientific literature [15, 16]. Cerebellar syndrome is usually omitted from the list of clinical manifestations that announce osmotic brain injury; and on the other hand, EPM is not included in the differential diagnosis of the cerebellar syndromes. Therefore, this rare form of EPM may be overlooked in clinical practice. Given the present evidence, clinicians should be aware of this diagnosis in a patient presenting with cerebellar deficit after electrolyte imbalances [16]. Spinal CPM/EPM Osmotic demyelination affecting the spinal cord remains almost anecdotic, with the first reference dating back to 1985, reported by Zwick et al. [17], who described four autopsy cases with spinal findings compatible with the osmotic injury seen in the classic supratentorial CPM [17]. These patients, all alcoholic individuals, were considered as affected by spinal myelinolysis with predominant lesions in the posterior columns of the cervical spinal cord segments [17]. In our patient, as in all Zwick’s cases, the typical presentation of an injury confined to the spinal cord was absent, which is incompatible with other etiologies that may resemble the neuroimaging findings described in our patient. Also, a non-inflammatory CSF and negativity to NMO-IgG/anti-AQP4 exclude the neuromyelitis optica spectrum [18, 19]. In 1998, Pneumatikos et al. [20] reported a quadriplegic patient with cervical spinal EPM confirmed by MRI, associated with hypernatremia. Moreover, neither Zwick et al. nor Pneumatikos et al. reported that their patients had simultaneous CMP. In our patient, the concomitant CPM and spinal EPM strongly suggest ODS diagnosis. To our knowledge, this is the first case reported with this particular characteristic. In conclusion, clinicians should be aware of atypical clinical and radiological findings in the context of known risk factors for osmotic demyelination. Our observations may help to expand the list of clinical syndromes associated with osmotic central nervous system injury. Conflict of interest None.
  • Author's personal copy Acta Neurol Belg References 1. Adams RD, Victor M, Mancall EL (1959) Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. Arch Neurol Psychiatry 81:154–172 2. Wright DG, Laureano R, Victor M (1979) Pontine and extrapontine myelinolysis. Brain 102:361–385 3. Pradhan S, Jha R, Singh MN, Gupta S, Phadke RV, Kher V (1995) Central pontine myelinolysis following ‘slow’ correction of hyponatremia. Clin Neurol Neurosurg 97:340–343 4. Martin RJ (2004) Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry 75(Suppl 3):iii22–iii28 5. Kilinc M, Benli US, Can U (2002) Osmotic myelinolysis in a ¸ normonatremic patient. Acta Neurol Belg 102:87–89 6. Miller GM, Baker HL Jr, Okazaki H, Whisnant JP (1988) Central pontine myelinolysis and its imitators: MR findings. Radiology 168:795–802 7. Calakos N, Fischbein N, Baringer JR, Jay Ch (2000) Cortical MRI findings associated with rapid correction of hyponatremia. Neurology 55:1048–1051 8. Rouanet F, Tison F, Dousset V, Corand V, Orgogozo JM (1994) Early T2 hypointense signal abnormality preceding clinical manifestations of central pontine myelinolysis. Neurology 44:979–980 9. Newell KL, Kleinschmidt-DeMasters BK (1996) Central pontine myelinolysis at autopsy; a twelve-year retrospective analysis. J Neurol Sci 142:134–139 10. Shoji M, Kimura T, Ota K, Ohta M, Sato K, Yamamoto T et al (1996) Cortical laminar necrosis and central pontine myelinolysis in a patient with Sheehan syndrome and severe hyponatremia. Intern Med 35:427–431 11. Susa S, Daimon M, Morita Y, Kitagawa M, Hirata A, Manaka H et al (1999) Acute intermittent porphyria with central pontine myelinolysis and cortical laminar necrosis. Neuroradiology 41: 835–839 12. Cho AH, Choi CG, Lee SA (2005) Cortical laminar necrosis associated with osmotic demyelination syndrome. J Clin Neurol 1:174–176 13. Roh JH, Kim JH, Oh K, Kim SG, Park KW, Kim BJ (2009) Cortical laminar necrosis caused by rapidly corrected hyponatremia. J Neuroimaging 19:185–187 14. Lewohl JM, Wang L, Miles MF, Zhang L, Dodd PR, Harris RA (2000) Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin Exp Res 24:1873–1882 15. Garzon T, Mellibovsky L, Roquer J, Perich X, Diez-Perez A (2002) Ataxic form of central pontine myelinolysis. Lancet Neurol 1:517–518 16. Kim J, Song T, Park S, Choi IS (2007) Cerebellar peduncular myelinolysis in a patient receiving hemodialysis. J Neurol Sci 253:66–68 17. Zwick D, Friede RL, Roessmann U (1985) Central spinal myelinolysis. Neurology 35:891–893 ´ 18. Chiquete E, Navarro-Bonnet J, Ayala-Armas R, Gutierrez-Gut´ ´ ´ ´ ´ ierrez N, Solorzano-Melendez A, Rodrıguez-Tapia D, Gomez´ Rincon M, Ruiz-Sandoval JL (2010) Neuromyelitis optica: a clinical update. Rev Neurol 51:289–294 ˇ 19. Habek M, Adamec I, Pavlisa G, Brinar VV (2012) Diagnostic approach of patients with longitudinally extensive transverse myelitis. Acta Neurol Belg 112:39–43 20. Pneumatikos J, Frangides C, Malizos K, Tsagourias M, Nakos G (1998) Acute myelinolysis in the cervical spinal cord. J Trauma 44:562–564 123