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CT scan findings and risk factors in patients presenting with stroke.

Byline: Nisar Khan, Habibullah Khan and Nowshad Khan

: Abstract

Background Cerebrovascular accident or stroke is one of the three leading causes of death globally. Differentiation between cerebral infarction and haemorrhage is important because management depends on the correct diagnosis. There are many risk factor which predispose a person to stroke. The objective of this study was to know the frequency of cereberal haemorrhage and infarction in stroke patients and to know the risk factors for stroke in our community.

Material and Methods: This descriptive study was conducted on 47 patients of stroke admitted at DHQ Teaching Hospital, D.I.Khan, Pakistan, from November 2011 to April 2012. Patients of any age who developed focal neurological event lasting more than 24 hours, due to vascular event in the brain were included. Those with any other cause for focal neurological deficit were excluded. The data was collected on proforma and descriptive statistics applied to analyze the data.

Results: The mean age of patients was 54.5+9.66 years with a range of 17-75 years. Out of 47 patients 21 were males and 26 females. CT scan of brain showed 26(55.31%) cases of cerebral infarction and 21(44.68%) intracranial haemorrhage. Regarding risk factors, 37 patients were hypertensive, 9 had ischemic heart disease and 6 had diabetes mellitus.

Conclusion: In our study, among patients with stroke, 45% were having intracranial haemorrhage, while 55% cerebral infarction. Hypertension was the most common risk factor, followed by ischemic heart diseases and diabetes mellitus.

KEY WORDS: CT scan; Stroke; Hypertension; Ischemic heart disease; Diabetes mellitus.INTRODUCTION

Cerebrovascular accident (CVA) or stroke is one of the three leading causes of death in the world along with cancer and heart disease.1 Between1990 and 2010 the number of strokes decreased by approximately 10% in the developed world but increased in the developing world. Overall two thirds of strokes occur in those over 65 years of age.2,3

Distinction between intracerebral haemorrhage and infarction is important because proper management of acute stroke syndrome is based on the correct diagnosis of the pathological type. Computed tomography (CT) is an accurate, safe and noninvasive procedure to differentiate between cerebral infarction and hemorrhage.4 It also showsthe correct site of the lesion and is superior to MRI for detecting the intracranial haemorrhage of less than 48 hour duration.5

Although the classical features of intracerebral haemorrhage e.g. sudden-onset of severe headache, vomiting, rapid deterioration of consciousness and lack of previous transient ischemic attacks are reasonably specific for haemorrhage, yet CT scan is sensitive for smaller peripheral haemorrhages that carry a better prognosis for survival and functional recovery.6 The reported incidence of intracranial haemorrhage is very high more than 40% in developing countries. This is in contrast to the 5-20% in the developed countries.7

Stroke can be prevented by treating important risk factors. Hypertension is an important risk factor for stroke, both intracranial haemorrhage and cerebral infarction. Its poor control may be an important reason for the high incidence of intracranial haemorrhage in our part of the world.The incidence of stroke in the Western world is decreasing. This is because of better health care, proper control of hypertension, and better management of other risk factors like heart diseases and diabetes mellitus. This study will help in the management of stroke patients.

The objective of this study was to know the frequency of cereberal haemorrhage and infarction in stroke patients and to know the major risk factors for stroke in our community.

MATERIAL AND METHODS

This was a descriptive study conducted at Department of Medicine, DHQ Teaching Hospital, D.I. Khan, Pakistan, from November, 2011 to April,2012. A sample size of 47 patients was selected by purposive sampling technique. All patients with focal neurological deficit due to vascular event in the brain were included in the study. Those with focal neurological signs due to space occupying lesions on CT scan were excluded from the study.

History and clinical examination were recorded and all the findings were entered into a proforma. The demographic variables were gender and age in years. The research variables were hypertension, ischemic heart disease and diabetes mellitus. Descriptive statistics were applied to analyze the data.

RESULTS

The mean age of patients was 54.5+9.66 years, with a range of 17-75 years. Out of 47 patients 21 were males and 26 females, with a male to female ratio of 1:1.2.

CT scan of brain showed 26 (55.31%) cases of cerebral infarction and 21 (44.68%) intracerebral haemorrhage.

In regard to risk factors, 37 patients were having hypertension, 9 ischemic heart disease, and 6 diabetes mellitus. (Table 1)

DISCUSSION

We found in this study that the percentage of

Table 1: Frequency of risk factors among###

###patients with stroke (n=47).###

###Findings of###Risk Factors###

###CT scan###

###Hyper###Ischemic###Diabetes###

###tension###Heart###Mellitus###

###disease

###Infarction###18###7###4###

###Haemorrhage###19###2###2###

###Total###37###9###6

intracerebral haemorrhage and infarction varied considerably from the studies in developed countries but varied little from the studies conducted in the developing countries like Thailand and India. Cerebral haemorrhage is found in 20% of the patients with stroke in developed countries but in developing countries, like Pakistan hemorrhage is quite common, partly because of poorly controlled hypertension.11,12

Haemorrhage was present in 40.8% and Cerebral infarction in 50% in a study from Swat district by Mumtaz et al13 which is similar to our study in which cerebral infarction was present in 55.31% and cerebral haemorrhage in 44.68%. In our study the frequency of cerebral infarction and cerebral haemorrhage were similar to the study conducted in Thailand showing 40-50% cases of cerebral haemorrhage and50-60% cases of cerebral infarction. Also in a study from India the percentage of intracerebral haemorrhage and infarction was similar to those of ours i.e.42.5% for haemorrhage and 57.5% for infarction.14

In our study hypertension was the commonest risk factor present in 78.72% of patients followed by ischemic heart disease in 19.14% and diabetes mellitus in 12.76%, which is similar to that of the study by Mumtaz et al13 in which hypertension was present in 75% of patients followed by ischemic heart diseases and diabetes mellitus. In our study, hypertension was the most common risk factor, not only in haemorrhage but also in cases of cerebral infarction. This finding is similar to a study by Thacker et al from India.15

CONCLUSION

In our community, among patients with stroke,45% are having intracranial haemorrhage while 55% cerebral infarction. Hypertension is the most common risk factor, followed by ischemic heart diseases and diabetes mellitus.

REFERENCES

1. Viroslar AB, Hoffman JC Jr. The use of C.T in the diagnosis of stroke. Heart dis Stroke 2009; 2:299-307.

2. The top 10 causes of death. WHO.http://who.int/mediacentre/factsheets/fs310/en/ accessed on26 Dec 2013.

3. Feign VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of stroke during 19902010: findings from the Global Burden of Disease Study2010. The Lancet, Early Online Publication, 24 October 2013.doi:10.1016/S0140-6736(13)61953-4.

4. Cassidy TP, Lewis S, Gray CS. Computerized tomography and stroke. Scott Med J 2010; 38:136-8.

5. Kim JS, Lee JH, Lee MC. Small primary intracerebralhaemorrhage, clinical presentation of 28 cases. Stroke 2007; 25: 1500-6.

6. Harison MJG. Clinical distinction of cerebral haemorrhage and cerebral infarction. Postgard Med J 1999; 56: 436-56.

7. Stevens JM, Barber CJ, Kersslake R. Extended use of cranial C.T. in the evaluation of patients with stroke and TIAs. Neuroradialogy 2007; 33:200-6.

8. Sandercock P, Bamford J, Dennis M, Burn J, Slattery J, Jones L, et al. Atrial fibrillation and stroke; prevalence in different type of stroke and influence on early and long term prognosis (Oxfordshire Community Stroke Project). BMJ 1992;305: 1460-5.

9. Wolf PA. Atrial fibrillation as an independent risk factor for stroke, the Framingham study. Stroke2008; 22: 983.

10. Feldmann E, Gordon N, Brooks JM. Factor associated with early presentation of acute stroke. 11. Daga MK, Sarin K, Negi VS. Comparison of siriraj and Guys Hospital score to differentiate supratentorial ischemic and haemorrhagic stroke in the Indian population. J Assoc Physicians India1994; 42: 302-3.

12. Viriyavejakul A, Pourigvarin N. Internal medicine patient: an analysis of incidence and mortality rate of 27325 admissions. Siriraj Hospital Gazette2007; 34: 501-10.

13. Marwat MA, Usman M, Hussain M. Stroke and its relationship to risk factors. Gomal J Med Sci2009; 7: 17-21.

14. Thacker AK, Radha Krishnan K, Maloo JG. Clinical and CT analysis of intracerebral haemorrhage. J Assoc Physicians India 1998;

ZCZC PREVENTION OF HEPATOTOXICITY OF VALPROIC ACID WITH CONCOMITANT SUPPLEMENT OF CARNITINE: AN EXPERIMENTAL STUDY IN ALBINO RATS

By: Syed Khanzada Khan, Shahida Tasneem, Naila Ismail, Purdil Khan amd Kazi Abdul Shakoor

_: ABSTRACT

Background Valproic acid is an antiepileptic drug which may cause carnitine deficiency and subsequently hepatotoxicity in the form of necrosis and steatosis. The objective of this study was to observe the protective role of carnitine against valproic acid induced hepatotoxicity in albino rats.

Material and Methods: This was an experimental study of concurrent parallel design in albino rats, carried out in Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. Thirty adult and apparently healthy albino rats were selected. The animals were divided into five equal groups; Group A control, kept on the diet of animal house only, Group B treated with therapeutic doses of valproic acid + carnitine supplement, group C treated with toxic doses of valproic acid + carnitine supplement, Th group treated with therapeutic doses of valproic acid and Tx group treated with toxic doses of valproic acid. All the animals were fed on routine diet of animal house and sacrificed after 3 weeks of treatment. The liver of each animal was properly fixed, sectioned, processed, stained with H and E stain and seen under light microscope.

Results: No significant changes in the livers were seen in group A. Focal necrosis was be seen in the liver of one out of six animals (16.66%) of group B, foci of steatosis were seen in one (16.66%) and necrosis in 3(50%) animals of group C whereas in Th group steatosis was seen in 5(83.33%) and necrosis in one (16.66%) and in Tx group steatosis in 5(83.33%) and necrosis in 2(33.33%).

Conclusion: Valproic acid induced hepatotoxicity in the form of steatosis can be prevented by carnitine supplement in albino rats.

KEY WORDS: Valproic acid; Carnitine; Hepatic steatosis.INTRODUCTION

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is effective in the treatment of many types of partial and generalized epileptic seizures. VPA is an eight carbon branched chain fatty acid having a broad spectrum of anticonvulsant activity, thus indicated in the treatment of epilepsy. Its chemical structure resembles to that of short chain fatty acids. The formula of VPA is C H O .1 Its mechanism of action includes enhancedneurotransmission of gamma amino-butyric acid. However, several other mechanisms of action in neuropsychiatric disorders have been proposed for VPA.2 Despite the pharmacological importance and effectiveness of VPA, its potential hepatotoxicity is a major concern.3

Acute VPA intoxication may occur as a consequence of intentional or accidental overdose. It usually results in mild and self-limited central nervous system depression. However, serious toxicity and even deaths have been reported.4 SevereVPA induced hepatotoxicity (VHT) in associationwith hepatic failure is rare, but it may develop an idiosyncratic reaction that is often fatal. Histological changes are similar to those observed in the Reye's syndrome, with early production of microvesicular steatosis followed by the development of centrilobular necrosis.5,6

VPA depletes carnitine stores, especially during long-term or high-dose therapy, through various synergistic mechanisms.7,8 A reduction in tubular reabsorption of both free carnitine and acylcarnitine has been reported during VPA treatment. Also the mitochondrial depletion of CoA-SH impairs AY-oxidation of fatty acids (and VPA) and ATP production. ATP depletion further impairs the function of the ATP-dependent membrane carnitine transporter.9

Raskind and El-Chaar extensively reviewed the pathophysiology and significance of VPA-induced carnitine deficiency and recommended carnitine supplementation during VPA therapy.10-12 Some experimental and clinical data suggest that early intravenous supplementation with L-carnitine could improve survival in severe VPA-induced hepatotoxicity.13 The objective of this study was to observe the protective role of carnitine against the valproic acid induced hepatotoxicity in albino rats.

MATERIAL AND METHODS

This experimental study was undertaken in Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi.

We selected 30 adult and apparently healthy albino rats of SpragueDwaley strain. The animals were divided into five equal groups; group A (control, kept on the diet of animal house only, Group B treated with therapeutic doses of VPA i.e. 35 mg/Kg/day, increased by 5-10 mg /kg/week and the supplement of carnitine in a dose of 60 mg/Kg/day and group C treated with toxic doses of VPA i.e. 85 mg/Kg/day, increased by 10-20 mg /kg/week and the supplement of carnitine in a dose of 100 mg/Kg/day. Th group animals were treated with therapeutic doses of VPA i.e. 35 mg/Kg/day, increased by 5-10 mg/kg/ week and Tx group were treated with toxic doses of VPA i.e. 85 mg/Kg/day, increased by 10-20 mg / kg/week. The animals were sacrificed after 3 weeks of treatment. The liver of each animal was properly fixed, sectioned, processed, stained with HandE and seen under the light microscope.

RESULTS

The histopathologic changes in the liver were observed as follows:

In group A (control), the lobular architecture was intact in 5 (83.33%) and focally altered in 1 (16.66%) due to parasitic cyst. No other significant changes such as focal necrosis or steatosis were observed. In group B (therapeutic regimen of VPA+ carnitine), the lobular architecture was intact in4 (66.66%) animals, however one animal showedparasitic cyst, while the other one revealed focal (midzonal) necrosis. No steatosis was observed. In group C (toxic regimen of VPA + carnitine), the lobular architecture was intact in 3 (50%) animals. However microvesicular steatosis was seen in one (16.66%) and focal necrosis in 3 (50%). In Th group (therapeutic regimen of VPA) steatosis was seen in5 (83.33%) animals and necrosis in 1(16.66%). In Tx group (toxic regimen of VPA) steatosis was seen in 5 (83.33%) animals and necrosis in 2 (33.33%). (Table1 and Fig 1).

Table 1: Comparison of histopathologic changes in the livers of albino rats induced by VPA alone and with supplement of carnitine.

Group###Percentage Percentage

###of steatosis of necrosis

A (Control)###0###16.66

Th (Animals treated###83.33###16.66

with therapeutic dos

age of VPA only)

B (Animals treated

with therapeutic dos

age of VPA+ supple-

C (Animals treated###16.66###50

with toxic dosage of

DISCUSSION

Several drugs including VPA are associated with decreased carnitine levels and occasionally with true carnitine deficiency.14 VPA depletes carnitine stores, especially during long-term or high-dose therapy, through various mechanisms.15 VPA induced histological changes in the liver are in the form of microvesicular steatosis and centrilobular necrosis.16Among cases of severe hepatotoxicity occurring during VPA therapy, survival has been reported mainly in those patients treated with carnitine.17-19

In this study we supplemented carnitine with VPA in the therapeutic (group B) and toxic (group C) regimens of VPA. We observed no steatosis in group A and B and 16.66% in group C as compared to 83.33% of steatosis in animals treated with therapeutic and toxic regimens of VPA alone. Similarly, no focal necrosis was seen in controls. However, there was 16.66% of focal necrosis in group B (VPA+ supplement of carnitine) equal to the effect of VPA alone (See Table 3), 50% in group C i.e. increased as compared to toxic regimen of VPA alone, which was 33.33% only. The protective role of carnitine in the form of necrosis was not significant.

Our findings in the form of steatosis are in agreement with the results reported by DeVivo et al15 and Nishida et al,18 that carnitine prevents VPA toxicity. Our findings regarding the necrosis are in accordance to the results of Fujimiya and Abbott19 that carnitine deficiency cannot be the only reason for fatal VPA induced hepatotoxicity. VPA-induced lipid peroxidation and glutathione depletion could also contribute to hepatotoxicity.20

CONCLUSION

Valproic acid induced hepatotoxicity in the form of steatosis can be prevented by carnitine supplement in albino rats.

REFERENCES

1. Johannessen CU, Johannessen SI. Valproate:past, present, and future. CNS Drug Rev 2003; 9:199-216.

2. Rosenberg G. The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci 2007; 64:2090-103.

3. Watkins PB, Seeff LB. Drug-induced liver injury: summary of a single topic clinical research conference. Hepatology 2006; 43: 618-31.

4. Spiller HA, Krenzelok EP, Klein-Schwartz W, Winter ML, Weber JA, Sollee DR, et al. Multicenter case series of valproic acid ingestion: serum concentrations and toxicity. J Toxicol Clin Toxicol 2000; 38: 755-60.

5. Andersen GO, Ritland S. Life threatening intoxication with sodium valproate. J Toxicol Clin Toxicol1995; 33: 279-84.6. Borum PR, Bennett SG. Carnitine as an essential nutrient. J Am Coll Nutr 1986; 5: 177-82.

7. Scaglia F. Longo N. Primary and secoudary alterations of neonatal carnitine metalboism. Semin Perinatol 1999; 23: 152-61.

8. Matsubara M, Ishihara T, Takeyama N, Tanaka T. Valproic acid overdose and L-carnitine therapy. J Anal Toxicol 1996; 20: 55-8.

9. Matsuda I, Ohtani Y. Carnitine status in Reye andReye-like syndromes. Pediatr Neurol 1986; 2:90-4.

10. Raskind JY, El-Chaar GM. The role of carnitine supplementation during valproic acid therapy. Ann Pharmacother 2000; 34: 630-8.

11. De Vivo DC, Bohan TP, Coulter DL. Dreifuss FE, Greenwood RS, Nordli DR, et al. L-carnitine supplementation in childhood epilepsy: current perspectives. Epilepsia 1998; 39: 1216-25.

12. LheureuxPE, Hantson P. Carnitine in the tratment of valpric acid-induced toxicity. Clin Toxicol (Philer) 2009; 47: 101-11.

13. Chen G, Bohner B, Enser CR. Evaluation of five methods for testing anticonvulsant ativities. Pros Soci Exp Bio Med 1956; 334-9.

14. Matsubara M, Ishihara T, Takeyama N, Tanaka T. Valproic acid overdose and L-carnitine therapy. J Anal Toxicol 1996; 20: 55-8.

15. DeVivo DC. Effect of L-carnitine treatment for valproate-induced hepatotoxicity. Neurology 2002;58: 507-8.

16. Kato A. Carnitine deficiency with valproate sodium therapy the difference by normal diet and enteral nutrition. No To Hattatsu 2013; 45: 17-20.

17. Xiong H, Liu CT, Zhang YH, Bao XH, Jiang YW, Zhao H, et al. Valproic acid-induced idiosyncratic liver injury in 4 cases. Zhonghua Er Ke Za Zhi2012; 50: 890-4.

18. Nishida N, Sugimoto T, Araki A, Woo M, Shakano Y, Kobayashi Y. Carnitine metabolism in valprovate treated rats: the effect of L-carnitine supplementation. Pediatr Res 1987; 22: 500-3.

19. Fujimiya T, Abbott FS. Fluorinated analogues as mechanistic probes in valproic acid hepatotoxicity: hepatic microvesicular steatosis and glutathione status. Chem Res Toxicol 1995; 8: 671-82.

20. Laub MC, Paetzke-Brunner I, Jaeger G. Serum carnitine during valproic acid therapy. Epilepsia 1986; 27: 559-62.
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Author:Khan, Nisar; Khan, Habibullah; Khan, Nowshad
Publication:Gomal Journal of Medical Sciences
Article Type:Report
Geographic Code:9PAKI
Date:Jul 3, 2014
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