Central pontine myelinolysis laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Overview

Laboratory finding consistent with the diagnosis of central pontine myelinolysis is hypoosmotic hyponatremia and the rapid correction of hyponatremia is the cause of central pontine myelinolysis.

Laboratory Findings

Laboratory findings consistent with the diagnosis of central pontine myelinolysis include:[1]

SIAD syndrome

  • Etiologies of SIAD:
Conditions
Malignant disorders Carcinoma: Lung ( small cell carcinoma, mesothelioma), oropharynx, stomach, duodenum, pancreas, ureter, bladder, prostate, endometrium, thymoma

Lymphomas

Sarcomas: Ewing's sarcoma

Olfactory neuroblastoma

Pulmonary diseases Infections: Bacterial pneumonia, viral pneumonia, pulmonary abscess, tuberculosis, aspergillosis

Others: Asthma, cystic fibrosis, respiratory failure, emphysema, COPD, positive-pressure ventilation

CNS disorders Infections: Encephalitis, meningitis, brain abscess, RMSF, AIDS, malaria

Vascular and SOP: Subarachnoid hemorrhage, stroke, brain tumors, head trauma

Others: Hydrocephalus, cavernous sinus thrombosis, Multiple sclerosis, Guillain–Barré syndrome, Shy–Drager syndrome,

delirium tremens, acute intermittent porphyria, chronic psychosis, pituitary stalk section, transsphenoidal adenomectomy

Other causes Hereditary: Gain-of-function mutation of V2 receptors

Idiopathic

Drugs

Transient: Exercise, general anesthesia, nausea, pain, stress


  • Causes of acute hyponatremia:
Etiology
  • Post operative phase
  • Transurethral or endoscopic procedure (mannitol, sorbitol, glycine)
  • Colonoscopy preparation
  • Polydipsia
  • Exercise
  • Oxytocin
  • Cyclophosphamide
  • Ecstasy( 3,4-Methylenedioxymethamphetamine, MDMA)
  • Thiazide
  • Halopridol
  • Recently started desmopressin, terlipressin, vasopressin

( Etiologies that cause hyperacute and acute hyponatremia are applicable to each category interchangeably depending on the onset of symptoms)

  • Causes of Hyponatremia based upon Serum Osmolality:
Classification Serum Osmolality Etiology
Hypertonic or Isotonic Hyponatremia > 295 mOsm/kg Hyperglycemia, Mannitol, Glycine, Maltose, severe azotemia
Isotonic Hyponatremia

(Pseudohyponatremia)

275 – 295 mOsm/kg Lab/blood draw error, Post TURP (bladder irrigation with osmotic solutions),

intravenous immunoglobulin (IVIg), Hyperlipidemia ( triglyceride, cholesterol ),

hyper paraproteinemia (monoclonal gammopathy of undetermined significance (MGUS),

multiple myeloma),

Hypotonic Hyponatremia < 275 mOsm/kg Glycerol, Sorbitol, Etiology depends upon volume status (Hypervolemic/ Euvolemic/ Hypovolemic)
Alcohol, Urea, Ethylen glycol are ineffective osmoles, cause hyperosmolar isotonic serum but not hyponatremia.

‡ Hyperglycemia causes osmotic diuresis results in a rise in serum sodium concentration, on the other hand it leads to extracellular shift of water due to osmotic gradient which causes relative hyponatremia , depends on which effect is stronger, there would be hypertonicity or hypotonicity[2].

  • Causes of Hyponatremia based on volume status [3] :
Volume status Sodium status Causes
Hypovolemic

Hyponatremia[4]

  • total body water ↓
  • total body sodium ↓↓
  • GI loss: Vomiting, diarrhea, tube drainage
  • Insensible loss: Sweating, burns
  • Renal loss: Salt-wasting nephropathy (inappropriate loss of Na+-Cl– in the urine),

bicarbonaturia ( renal tubular acidosis, metabolic alkalosis), osmotic diuresis, diuretic use,

cerebral salt-wasting syndrome (Stroke ,SAH ,↑ brain natriuretic peptide and ↑ renal sodium loss )

  • Excessive diuretic administration
Hypervolemic

Hyponatremia

  • total body water ↑↑
  • total body sodium ↑
  • Renal disease: Acute or chronic kidney disease or injury

(due to relatively higher water versus salt intake and poor excretion), nephrotic syndrome

  • Congestive heart failure
  • Cirrhosis
  • Iatrogenic
Euvolemic

Hyponatremia

  • total body water ↑
  • total body sodium ↔

postoperative nausea, pain, stress, neoplasia (common), trauma, pregnancy)

, nephrogenic SIAD (Gain-of-function mutation of v2 receptors)

  • High fluid intake: Physical activity, surgery, primary polydipsia, potomania, tea & toast diet

(caused by a low intake of solutes with relatively high fluid intake)

  • Reset osmostat  : Drugs, pregnancy
  • Iatrogenic

† Altered sensitivity to serum osmolality by the hypothalamic osmoreceptors

  • Drugs which cause hyponatremia:
Drug Mechanisms [5] Drug Classification
Increase ADH secretion Antidepressants:Tricyclic antidepressants ( Amitryptiline,

Protriptyline, Desipramine),Selective serotonin reuptake inhibitors,

Monoamine oxidase inhibitors

Antipsychotic drugs: Phenothiazines (Thioridazine, Trifluoperazine),

Butyrophenones (Haloperidol)

Antiepileptic drugs: Carbamazepine, Oxcarbazepine, Sodium valproate

Anticancer agents: Vinca alkaloids (Vincristine, Vinblastine),

Platinum compounds (Cisplatin, Carboplatin)

Alkylating agents: Intravenous Cyclophosphamide, Melphalan, Ifosfamide

Miscellaneous: Methotrexate, Interferon, Levamisole, Pentostatin, Monoclonal antibodies, MDMA, Nicotine

Opiates

Increase ADH effect Antiepileptic drugs: Carbamazepine, Lamotrigine

Antidiabetic drugs: Chlorpropamide, Tolbutamide

Anticancer agents: Alkylating agents (Intravenous cyclophosphamide)

NSAIDS

Drugs affecting water and sodium homeostasis Diuretics: Thiazides, Indapamide, Amiloride, Loop diuretics
Reset omostat Antidepressants: Venlafaxine

Antiepileptic drugs: Carbamazepine

Vasopressin analogues Desmopressin, oxytocin, terlipressin, vasopressin

Altered sensitivity to serum osmolality by the hypothalamic osmoreceptors

Causes by Organ System

Cardiovascular Congestive heart failure
Chemical / poisoning No underlying causes
Dermatologic Burns
Drug Side Effect ACE inhibitors, Ajuga nipponensis makino , Asenapine maleate, Cefpodoxime, Chlorpropamide, Cyclophosphamide, Desmopressin, Diuretics, Duloxetine, Eslicarbazepine acetate, Ethacrynic Acid, Felbamate, Fluvoxamine, Interferon gamma, Ixabepilone, Losartan and Hydrochlorothiazide, Nilotinib, Nivolumab, Nonsteriodal anti-inflammatory drugs , Oxcarbazepine, Pramipexole, Rifaximin, Tiagabine, Tolazamide, Zonisamide, Tolbutamide, Vortioxetine
Ear Nose Throat No underlying causes
Endocrine Addison's disease, Corticosterone methyloxidase type I deficiency , Diabetes mellitus, Diabetic coma, Glucocorticoid deficiency, Familial hyperreninemic hypoaldosteronism type 2, Hypothyroidism, Mineralocorticoid deficiency, Myxedema coma , Syndrome of inappropriate antidiuretic hormone , Thyrotropin deficiency, 18-Hydroxylase deficiency , Familial hypoaldosteronism
Environmental No underlying causes
Gastroenterologic Acute liver failure , Cirrhosis, Congenital chloride diarrhea , Diarrhea, Gastrointestinal fistula, Ileus, Necrotizing enterocolitis , Pancreatitis, Peritonitis, Vomiting, Cystic fibrosis
Genetic 18-Hydroxylase deficiency , Bartter Syndrome type 4 , Cystic fibrosis, Familial hypoaldosteronism , Corticosterone methyloxidase type I deficiency , Familial hyperreninemic hypoaldosteronism type 2, Congenital chloride diarrhea
Hematologic No underlying causes
Iatrogenic After pituitary surgery, After surgery, Ascitic tap, Gastric drainage, Hypotonic infusions, Pleuracentesis
Infectious Disease Malignant boutonneuse fever , Neonatal bacterial meningitis , Peritonitis
Musculoskeletal / Ortho No underlying causes
Neurologic Intracranial hemorrhage, Subarachnoid hemorrhage, Pituitary cancer
Nutritional / Metabolic Hyperlipidemia, Hyperproteinemia, Hypoalbuminemia, Low sodium diet, Metabolic acidosis, Diabetic coma
Obstetric/Gynecologic Pregnancy
Oncologic Pituitary cancer
Opthalmologic No underlying causes
Overdose / Toxicity Water intoxication
Psychiatric Psychogenic polydipsia, Psychosis, Self-induced water intoxication and schizophrenic disorders syndrome
Pulmonary Cystic fibrosis
Renal / Electrolyte Acute kidney disease, Chronic kidney disease, Diuresis, Glucosuria, Ketonuria, Nephrotic syndrome, Renal Tubular Acidosis, Tubulointerstitial kidney disease, Bartter Syndrome type 4 , Corticosterone methyloxidase type I deficiency , Renal failure
Rheum / Immune / Allergy Addison's disease, Nephrotic syndrome
Sexual Cystic fibrosis
Trauma Burns
Urologic No underlying causes
Dental No underlying causes
Miscellaneous Beer potomania, Ecstasy abuse , Factitious hyponatremia, Hydration, Massive edema, Pseudohyponatremia, Water Intoxication , Hyperlipidemia, Hyperproteinemia, Hypoalbuminemia, Exercise associated hyponatremia

Causes in Alphabetical Order

References

  1. Burgetova A, Vaneckova M, Seidl Z, Dolezal O (2008). "Osmotic demyelination syndrome (central pontine and extrapontine myelinolysis with coagulative necrosis of the putamina and cortical laminar necrosis). A case report and review of the literature". Neuroradiol J. 21 (4): 521–6. doi:10.1177/197140090802100409. PMID 24256958.
  2. A. I. Arieff & H. J. Carroll (1972). "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases". Medicine. 51 (2): 73–94. PMID 5013637. Unknown parameter |month= ignored (help)
  3. Guillaumin, Julien; DiBartola, Stephen P. (2017). "A Quick Reference on Hyponatremia". Veterinary Clinics of North America: Small Animal Practice. 47 (2): 213–217. doi:10.1016/j.cvsm.2016.10.003. ISSN 0195-5616.
  4. Rondon-Berrios, Helbert; Agaba, Emmanuel I.; Tzamaloukas, Antonios H. (2014). "Hyponatremia: pathophysiology, classification, manifestations and management". International Urology and Nephrology. 46 (11): 2153–2165. doi:10.1007/s11255-014-0839-2. ISSN 0301-1623.
  5. Liamis, George; Milionis, Haralampos; Elisaf, Moses (2008). "A Review of Drug-Induced Hyponatremia". American Journal of Kidney Diseases. 52 (1): 144–153. doi:10.1053/j.ajkd.2008.03.004. ISSN 0272-6386.

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