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Table of Contents    
ORIGINAL ARTICLE
Year : 2013  |  Volume : 61  |  Issue : 5  |  Page : 467-471

Spectrum of neurological complications in HELLP syndrome


1 Department of Neurology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Obstetrics and Gynecology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Critical Care Division, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission04-Mar-2013
Date of Decision24-Jul-2013
Date of Acceptance11-Oct-2013
Date of Web Publication22-Nov-2013

Correspondence Address:
Gunchan Paul
Associate Intensivist Critical Care Division, Dayanand Medical College, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.121909

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 » Abstract 

Background: Hemolysis (H), elevated liver enzymes (EL), and low platelets (LP), HELLP syndrome is the extended spectrum of severe preeclampsia and is associated with high mortality. A large proportion of mortality can be attributed to catastrophic central nervous system events. Aims: The purpose of this study was to access the clinical manifestations, radiological abnormalities and outcome in patients of HELLP syndrome with neurological manifestations. Setting: Obstetric unit and neurology intensive critical unit (ICU) of an academic medical center. Study Design: Retrospective study. Subjects and Methods: Case records of all obstetrical patients who were admitted between January 2012 and December 2012 were screened and data was collected from those patients who were diagnosed with HELLP syndrome with neurological complications. It was entered into a structured performa and analyzed using percentages . Results: During the study period; 1,166 deliveries were conducted, 108 patients had pregnancy-induced hypertension (PIH); and of the 12 patients with HELLP, eight (66%) patients had neurological complications. The presenting neurological features were seizures (four), focal neurological deficits (two), and encephalopathy (two). Of the eight patients, in six patients neuroimaging showed features of posterior reversible encephalopathy syndrome (PRES), three of them had associated hemorrhage, and two patients had isolated intracranial hemorrhage. All except two were discharged home. Conclusions: Neurological complications are not uncommon in patients with HELLP syndrome and a high index of suspicion is essential. Aggressive multidisciplinary approach is the key to reduce the morbidity and mortality.


Keywords: Eclampsia, intracranial hemorrhage, hemolysis (H), elevated liver enzymes (EL), and low platelets (LP) syndrome, neurological complications, posterior reversible encephalopathy syndrome


How to cite this article:
Paul BS, Juneja SK, Paul G, Gupta S. Spectrum of neurological complications in HELLP syndrome. Neurol India 2013;61:467-71

How to cite this URL:
Paul BS, Juneja SK, Paul G, Gupta S. Spectrum of neurological complications in HELLP syndrome. Neurol India [serial online] 2013 [cited 2019 Jun 26];61:467-71. Available from: http://www.neurologyindia.com/text.asp?2013/61/5/467/121909



 » Introduction Top


Hemolysis (H), elevated liver enzymes (EL), but low platelets (LP) define HELLP syndrome which is an extended spectrum of severe preeclampsia or eclampsia. [1] This syndrome is rare but can occur as an isolated condition in 0.2-0.6% of all pregnancies. [2] The reported mortality in HELLP syndrome varies from 1 to 25%, and is mainly attributed to disseminated intravascular coagulation (DIC), liver failure, adult respiratory distress syndrome, acute kidney injury, sepsis, stroke or cardiopulmonary arrest. [3] Concerning the neurological complications, there have been only a few case reports. This is an observational study of neurological manifestations in patients of HELLP syndrome.


 » Subjects and Methods Top


Study population consisted of 1,246 obstetrical patients hospitalized between January and December 2012. Case records of these patients were reviewed.

Definitions

Complete HELLP syndrome was defined as microangiopathic hemolytic anemia in women with severe preeclampsia, serum lactate dehydrogenase (LDH) >600 IU/L, platelet count <100,000/μL, and serum aspartate aminotransferase (AST) >70 IU/L. Partial HELLP was defined as the presence of only one or two of the features of LDH, AST or platelets. [4]

Based on the severity, HELLP syndrome was categorized into three classes using the University of Mississippi criteria: [5] Class 1 with severe thrombocytopenia (platelets <50,000/μL), evidence of hepatic dysfunction with AST or alanine aminotransferase (ALT) ≥70 IU/L and evidence suggestive of hemolysis (total serum LDH >600 IU/L); Class 2 required similar criteria except that thrombocytopenia was moderate (50,000-100,000/μL); and Class 3 included patients with mild thrombocytopenia (1-1.5 lac/μL), mild hepatic dysfunction (AST and/or ALT >40 IU/L) and hemolysis (LDH >600 IU/L).

Pregnancy-induced hypertension (PIH) was classically defined as the triad of hypertension (>140/90 mmHg), proteinuria, and edema after 20 weeks of gestation.

Posterior reversible encephalopathy syndrome (PRES) was defined as cerebral white matter edema seen as hypodensity on computed tomography (CT) or T2 weighted magnetic resonance imaging (MRI) showing hyperintensity at grey-white matter junction with no diffusion restriction.

Patients fulfilling the above criteria were included in the study and the following variables were entered in a structured proforma: i) Obstetrical features (age, parity, perinatal history, clinical presentation, laboratory findings, treatment details and complications) and associated comorbid conditions like hypertension, diabetes, and cigarette smoking; ii) neurological manifestations (headache, impairment of consciousness, seizures, focal neurological deficit and imaging abnormalities); iii) maternal outcome (discharge or death).


 » Results Top


During the 2 year period; 1,166 deliveries were conducted in our institute, 108 patients had PIH and 12 had HELLP syndrome. The frequency of HELLP syndrome in the total cohort was 0.9%. Of the 12 patients with HELLP syndrome, eight (66%) patients had neurological complications. The mean maternal age was 30.5 years. Five patients (62.5%) were multigravida and three (37.5%) were primigravida. [Table 1] gives the demographic profile, salient features of antenatal history, clinical and laboratory findings. Six (75%) patients had PIH and two patients (case II and VIII) had history of preeclampsia in previous pregnancies. Associated comorbidities were not observed in any. Six patients had complete HELLP, while the remaining two had partial HELLP, due to lack of peripheral blood film findings, although LDH levels were above 600 IU/L.
Table 1: Demographic data, presenting symptoms, salient features of history, lab parameters, and hospital stay of eight cases of HELLP syndrome

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Five (65%) patients developed neurological features in the postpartum period; while three patients (35%) presented in antepartum period. The presenting symptoms varied, the most common being generalized tonic-clonic seizures (four, 50%), hemiplegia (two, 25%), and encephalopathy (two, 25%). However, all the eight patients developed seizures during their hospital course. The neurological symptoms, neuroimaging findings and outcomes are summarized in [Table 2]. Two (25%) patients had isolated intracranial hemorrhage [Figure 1] and [Figure 2], six (75%) patients had features of PRES [Figure 3]a, [Figure 4], and [Figure 5]a, and three of them were associated with hemorrhage as well [Figure 3]b and [Figure 5]b.
Figure 1: Noncontrast computed tomography (CT) of case I showing hyperdensity in the interhemispheric fissure and bilateral cortical sulci suggestive of diffuse subarachnoid hemorrhage

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Figure 2: Noncontrast CT of case II shows a large intracerebral hemorrhage in the right parietal lobe, with mass effect

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Figure 3: (a) Magnetic resonance imaging fluid-attenuated inversion recovery (MRI FLAIR) image of case III demonstrates hyperintense signal in bilateral parietooccipital lobes also extending to the brain stem, suggestive of posterior reversible encephalopathy syndrome (PRES). (b) Four days later repeat MRI was done due to deterioration in sensorium. FLAIR images demonstrated hemorrhage in the right parietooccipital area

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Figure 4: MRI FLAIR image of case VII demonstrates vasogenic edema suggestive of PRES in the occipital, parietal, and frontal lobes; also involving the thalamus on both sides

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Figure 5: (a) MR image (T2 weighted) of case VIII shows bilateral hyperintense signal in parietooccipital area suggestive of PRES. (b) MRI (Gradient Echo) shows hemorrhage in the brainstem

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Table 2: Neurological symptoms, radiological findings, and outcome of eight cases of HELLP syndrome

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The clinical course of six patients was complicated by shock, five patients had acute kidney injury and three required mechanical ventilation. Platelet transfusions were given to five patients (case V and VII during laparotomy for hemoperitoneum, case II during parietal craniotomy for evacuation of intracranial hemorrhage (ICH), case IV and VIII for caesarean section).

Maternal outcome was good (75%) in all except two patients (case III and VIII). All except case II were managed conservatively with antihypertensives, antiepileptics and antiedema measures along with supportive care. Of the eight patients, four patients had still births (case II had twin pregnancy with one intrauterine death).


 » Discussion Top


The acronym of HELLP was first coined by Wenstein in 1982 to describe the presence of hemolysis (H), elevated liver enzymes (EL), and low platelets (LP) in a woman considered of having preeclampsia or eclampsia. [6] Using the University of Mississippi criteria [5] all the patients fulfilled the three characteristic features of this syndrome with six in Class I and two patients in Class II.

The mean maternal age in this series was 30.5 years comparable to the age reported in the series by Isler and colleagues. [7] The mean age of women with pregnancy related ICH was younger than women with ICH not related to pregnancy (28 vs 38 years). [8] Kittner, et al., also reported relative risk of puerperal ICH to be 28.3 compared to 2.5 during antepartum period. [9] In our series of the five patients with ICH, three patients presented in the postpartum period suggesting that postpartum is a high risk period for developing neurological complications, more so in multigravida with HELLP syndrome. Another study reported a high incidence in the postpartum period, while the study from Taiwan in Chinese women reported a higher incidence (58%) of pregnancy-related ICH in prepartum period. [10],[11]

Majority reports of PRES in the obstetrics and gynecology literature are a complication of severe preeclampsia/eclampsia. We could find only two case reports of PRES in patients with HELLP. [12]

PRES is a transient clinicoradiological syndrome, first noted in patients with hypertensive encephalopathy. [13] The exact pathogenesis of PRES remains incompletely understood and the most likely mechanism is vasogenic edema secondary to an acute increase in arterial blood pressure, which overwhelms the autoregulatory capacity of the cerebral vasculature causing arteriolar vasodilatation and endothelial dysfunction. [14],[15] This compromised capacity of autoregulation of the cerebral vasculature has been postulated as the mechanism of ICH in eclampsia and the increased concentrations of oxyhemoglobin derived from hemolysis in patients with HELLP might exaggerate this vascular response. [16],[17] Also, thrombocytopenia in the setting of HELLP could contribute to increased risk of hemorrhage in these patients. As the name suggests, there is predilection of vasogenic edema in PRES for the posterior white matter, because the anterior cerebral circulation has higher sympathetic innervations than the vertebrobasilar system, which is protective against the damaging hypertension. [18] However, edema may not be limited to the posterior circulation and changes may be widespread involving the brainstem also, as in our cases V and VII [Figure 3]a and [Figure 4]. Although complete reversibility of clinical and radiological features is the defining feature of PRES; however, ischemic injury and irreversible damage can occur. Hefzy et al., [19] studied the frequency of hemorrhage in PRES among various clinical conditions and reported an incidence of 5% in patients with eclampsia/delayed eclampsia. In our study one patient had initial imaging that was negative, while the other two had widespread changes of PRES along with hemorrhage.

Two-third of our patients were discharged with no neurological deficit and follow-up MRI showed complete resolution of previous changes, consistent with the diagnosis of PRES. The mainstay of treatment is recognition and removal of the precipitating factor and supportive care. Our patients were aggressively managed with anticonvulsants, antiedema measures, antihypertensives and termination of pregnancy (case IV and VI). Previous studies suggest a significantly higher incidence of postpartum hemorrhagic complications in patients with platelets count <40,000/m 3 . [20] Our observation suggests that platelets should be transfused if there is presence of significant bleeding, platelets count <50,000/m 3 severe thrombocytopenia resulting in spontaneous ICH or when emergent cesarean section is planned.

There are some limitations of this study, it is a retrospective analysis; the number of patients was very small and MRI could not be done in all patients which could reduce the detection of smaller hemorrhages. Also our experience is heavily influenced by referral bias. Many patients of HELLP with less severity might have been managed at the community level hospitals and some patients with complications might have been referred to other institutes. Thus, our study may not reflect the true incidence of HELLP and neurological complications.

 
 » References Top

1.Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993;169:1000-6.  Back to cited text no. 1
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2.Curtin WM, Weinstein L. A review of HELLP syndrome. J Perinatol 1999;19:138-43.  Back to cited text no. 2
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3.Kirkpatrick CA. The HELLP Syndrome. Acta Clin Belg 2010;65:91-7.  Back to cited text no. 3
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4.Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004;103:981-91.  Back to cited text no. 4
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5.Martin JN Jr, Rose CH, Briery CM. Understanding and managing HELLP syndrome: The integral role of aggressive glucocorticoids for mother and child. Am J Obstet Gynecol 2006;195:914-34.  Back to cited text no. 5
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6.Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: A severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982;142:159-67.  Back to cited text no. 6
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7.Isler CM, Rinehart BK, Terrone DA, Martin RW, Magann EF, Martin JN Jr. Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1999;181:924-8.  Back to cited text no. 7
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8.Bateman BT, Schumacher HC, Bushnell CD, Pile-Spellman J, Simpson LL, Sacco RL, et al. Intracerebral hemorrhage in pregnancy: Frequency, risk factors, and outcome. Neurology 2006;67:424-9.  Back to cited text no. 8
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9.Kittner SJ, Stern BJ, Feeser BR, Hebel R, Nagey DA, Buchholz DW, et al. Pregnancy and the risk of stroke. N Engl J Med 1996;335:768-74.  Back to cited text no. 9
    
10.Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium. A study in public hospitals of Ile de France. Stroke 1995;26:930-6.  Back to cited text no. 10
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11.Tanaka H, Ueda Y, Hayashi M, Date C, Baba T, Yamashita H, et al. Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community. Stroke 1982;13:62-73.  Back to cited text no. 11
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12.Vijayalakshmi B, Sethna F, Manford M, Lees CC. Posterior reversible encephalopathy syndrome in a patient with HELLP syndrome complicating a tripod pregnancy. J Matern Fetal Neonatal Med 2010;23:938-43.  Back to cited text no. 12
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13.Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: Prognostic utility of quantitive diffusion-weighted MR images. AJNR Am J Neuroradiol 2002;23:1038-48.  Back to cited text no. 13
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14.Strandgaard S, Olesen J, Skinhoj E, Lassen NA. Autoregulation of brain circulation in severe arterial hypertension. Br Med J 1973;1:507-10.  Back to cited text no. 14
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15.Dinsdale HB. Hypertensive encephalopathy. Neurol Clin 1983;1:3-16.  Back to cited text no. 15
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16.Sarrel PM, Lindsay DC, Poole-Wilson PA, Collins P. Hypothesis: Inhibition of endothelium-derived relaxing factor by haemoglobin in the pathogenesis of pre-eclampsia. Lancet 1990;336:1030-2.  Back to cited text no. 16
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17.Kobayashi T, Tokunaga N, Isoda H, Kanayama N, Terao T. Vasospasms are characteristic in cases with eclampsia/preeclampsia and HELLP syndrome: Proposal of an angiospastic syndrome of pregnancy. Semin Thromb Hemost 2001;27:131-5.  Back to cited text no. 17
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18.Port JD, Beauchamp NJ Jr. Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. Radiographics 1998;18:353-67.  Back to cited text no. 18
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19.Hefzy HM, Bartynski WS, Boardman JF, Lacomis D. Hemorrhage in Posterior reversible encephalopathy syndrome: Imaging and Clinical Features. AJNR Am J Neuroradiol 2009;30:1371-9.  Back to cited text no. 19
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20.Roberts WE, Perry KG Jr, Woods JB, Files JC, Blake PG, Martin JN Jr. The intrapartum platelet count in patients with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome: Is it predictive of later hemorrhagic complications. Am J Obstet Gynecol 1994;171:799-804.  Back to cited text no. 20
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]

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