Introduction:
Hyperemesis gravidarum is associated with long lasting and uncontrollable nausea and vomiting with the common complications like dehydration, ketosis, hypochloremia and hypocalcemia which may cause an increase in maternal mortality and morbidity. Wernicke’s encephalopathy which manifests with diplopia, amnesia, confusion, apathy and ophthalmoplegia is one of the rarest complication of hyperemesis gravidarum due to thiamine deficiency. Wernicke’s encephalopathy is usually associated with chronic alcoholism. Other causes include malnutrition, starvation, malignant diseases, intravenous feeding and consumption of thiamine deficient diet. Wernicke’s encephalopathy due to severe Hyperemesis gravidarum is reported uncommonly with the incidence of 0.1 – 0.5%.[1]
We present here a case of Wernicke’s encephalopathy due to Hyperemesis gravidarum with intrauterine death who recovered without any neurological sequelae due to timely diagnosis and appropriate treatment.
Case Report:
A 29 years old housewife presented to us in the 17th week of her second pregnancy with the history of altered sensorium. Further history obtained revealed that she had unsteadiness of gait few days prior to admission. She was treated as a case of Hyperemesis gravidarum as she had been vomiting since 8th week of her pregnancy continuously despite various antiemetics. There was no history of fever or alcohol consumption.
On admission she was drowsy and unable to obey simple commands. Her BP recorded 118/76 mm of Hg. However she moved all four limbs on painful stimuli. There was neither meningism nor cerebellar signs. The reflexes were normal with negative Babinski’s response. Nystagmus was present in both horizontal and vertical directions but the range of eye movements were normal. Ultrasound abdomen done revealed intrauterine foetal demise which was delivered completely by obstetrician through induction. Based on clinical findings differential diagnosis of sceptic encephalitis and cerebral venous thrombosis were thought of.
CSF analysis was normal. MRI Brain plain revealed bilateral symmetrical T2 and FLAIR hyperintensities noted in medial thalamus, tectum, mamillary bodies, hypothalamus and periaqueductal grey matter which was suggestive of Wernicke’s encephalopathy. MR Venography was normal. Other laboratory investigations were unremarkable.
 |
 |
Scan 1: Sagittal FLAIR image shows signal alterations involving lower tectal plate and mammilary bodies |
Sacn 2: Axial FLAIR image at the level of brainstem shows signal alterations in periaqueductal region tectal plate and mammilary bodies. |
As the clinical signs and MRI findings were consistent with Wernicke’s encephalopathy she was started with immediate IV thiamine replacement at the dosage of 300mg/day. There was no laboratory support for measurement of serum transketolase activity in the hospital. Her condition improved gradually over the next few days. Neurological examination done after 1 week showed remarkable improvement except for persistent mild ataxia which resolved over 2-3 weeks. This confirmed the diagnosis of Wernicke’s encephalopathy.
Discussion:
Wernicke’s encephalopathy is a metabolic disorder due to thiamine deficiency, first described by Carl Wernicke’s in 1881. He first reported a triad of symptoms consisting of drowsiness, ophthalmoplegia and ataxia in three patients. On autopsy, he detected punctuate haemorrhages affecting the grey matter around the third and fourth ventricles and aqueduct of Sylvius, and designated the term “polio - encephalitis hemorrhagica superioris”.[2]
In 1997, Caine et al proposed an operational criterion for the recognition and diagnosis of Wernicke’s encephalopathy accordingly; Wernicke’s encephalopathy is recognized if there are two of the following four signs; (i) dietary deficiencies, (ii) oculomotor abnormalities, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment.[3]
Although most cases of Wernicke’s encephalopathy seen today are related to chronic alcoholism, it is vital to recognise other rare causes of this condition, such as systemic diseases (malignancy, disseminated tuberculosis, acquired immunodeficiency syndrome (AIDS)), starvation (anorexia nervosa, prisoners of war, schizophrenia, terminally ill cancer patients), iatrogenic (refeeding after starvation, chronic haemodialysis), and persistent emesis such as hyperemesis gravidarum. The prevalence of Wernicke’s encephalopathy in a non-alcoholic patient varies from 0.04% to 0.13%.[4]
Wernicke’s encephalopathy in a patient with hyperemesis gravidarum was first described by Sheehan in 1939.[5] To our knowledge, very few cases of Wernicke’s encephalopathy during pregnancy have so far been reported in the literature.[6]
The mechanism by which thiamine deficiency causes the focal neuropathology lesions found in Wernicke’s encephalopathy might be multiple.[7] Thiamine is an important co-enzyme for three critical enzymes in the Kreb’s and pentose phosphate cycle: transketolase, ketoglutarate dehydrogenase, and pyruvate dehydrogenase complex. Deficiency of thiamine and hence deficiency of these enzymes result in focal lactic acidosis, cerebral energy impairment, depolarization of neurons due to n-methyl- D-aspartate receptor mediated excitotoxicity. Ultimately, it results in alteration of blood brain barrier, generation of free radical, prompting cell death by necrosis and apoptosis.[7]
The body has approximately 18 days of thiamine storage. It is well understood that thiamine requirements are increased during pregnancy, and even more by the impaired absorption due to hyperemesis gravidarum.[8] Thiamine dependence is also increased in conditions with high metabolic rates and high glucose intake, and therefore its depletion due to reduced intake as well as IV dextrose administration results in thiamine deficiency and Wernicke’s encephalopathy.[9,10]
The treatment for Wernicke’s Encephalopathy includes high doses of thiamine, 300 mg per day, given eighth hourly for two days followed by 250 mg per day once daily until the patient tolerates oral thiamine.[12]
Our patient presented with the classical clinical triad following intractable vomiting and dextrose administration without thiamine supplementation. MRI imaging also detected sensitive neurological changes, raising the suspicion of an acute stage of thiamine deficiency. These findings were important for prompt diagnosis and treatment of our patient’s condition. Indeed there are reports of the usefulness of MRI imaging in diagnosing cases of Wernicke’s encephalopathy.[11]
Wernicke’s encephalopathy should be suspected in any nutritionally compromised patient who shows altered mental status before manifestation of the classical triad as, if left untreated, it could lead to ever irreversible and persistent neurological sequela or death. We would like to emphasize the importance of prompt thiamine supplementation in pregnant women with prolonged vomiting in pregnancy, especially before starting intravenous or parenteral nutrition.
We would like to emphasize the importance of prompt thiamine supplementation in pregnant women with prolonged vomiting in pregnancy, especially before starting imtravenous or parenteral nutrition.
References:
- Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy. When should it be treated and what can be safely taken? Drug Saf 1998; 19; 155-64.
- Wernicke C. Lehrbuch der gehirnkrankheiten furaerzte und studirende. Kassel Theodor Fischer. 1881;2:229-42.
- Caine D, Halliday GM, Kril JJ, Harper CG. Operational criteria for the classification of chronic alcoholics:identification of Wernicke’s encephalopathy. JNNP. 1997;62:51-60.
- Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. AJR Am J Roentgenol 1998;171:1131-7.
- Sheehan HL. The pathology of hyperemesis gravidarum and vomiting of late pregnancy. J Obstet Gynecol British Commonwealth. 1939;46:685.
- Chiossi G, Neri I, Cavazzuti M, Basso G, Facchinetti F. Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature. Obstet Gynecol Surv. Apr 2006;61(4):255-68.
- Hazell AS, Todd KG, Butterworth RF. Mechanism of neuronal cell death in Wernicke’s encephalopathy. Metab Brain Dis. 1998;13:97-122.
- Togay-Isikay C, Yigit A, Mutluer N. Wernicke’s encephalo pathy due to hyperemesis gravidarum: an under-recognised condition. Aust N Z J Obstet Gynaecol. 2001;41:453-6.
- Munir A, Hussain SA, Sondhi D, Ameh J, Rosner F.Wernicke’s encephalopathy in a non-alcoholic man:case report and brief review. Mt Sinai J Med. 2001;68(3):216-8.
- Zimitat C, Nixon PF. Glucose loading precipitates acute encephalopathy in thiamine-deficient rats. Metab Brain Dis. 1999;14:1-20.
- Chung SP, Kim SW, Yoo IS. et al. Magnetic resonance imaging as a diagnostic adjunct to Wernicke’s encephalopathy in the ED. Am J Emerg Med. 2003;21:497-502.
- Chataway J, Hardman E. Thiamine in Wernicke’s syndrome – how much and how long? Postgrad Med J. 1995;71:249-53.
|
