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Fulminant Acute Disseminated Encephalomyelitis.

Byline: Hassan A. Alayafi1 Faisal R. Jahangiri1 MUkki Almuntashri

Abstract

Acute disseminated encephalomyelitis or post infectious encephalomyelitis is an immunologically mediated demyelinating disorder affecting the central nervous system after infection or vaccination. Young and adolescents are mostly affected with characteristic diffuse neurological signs. Prognosis is generally favorable however fulminant acute disseminated encephalomyelitis can be fatal if not diagnosed and treated early. With an increase in intracranial pressure the treatment o f choice is methylprednisolone followed by immunoglobulin plasmapheresis or cytotoxic drugs. We present a case of acute disseminated encephalomyelitis in a 17 year male who presented with a sudden onset recurrent generalized tonic-clonic seizures and rapidly become comatose. Magnetic resonance imaging along with other investigations helped in establishing the diagnosis. Treatment resulted in full recovery with uneventful follow up of four years.

Key words: ADEM Acute disseminated encephalomyelitis post infectious encephalomyelitis.

Introduction

Acute disseminated encephalomyelitis (ADEM) is a disorder with pathophysiology not fully understood however the most accepted etiology is an autoimmune response to myelin basic protein activated by infectious or vaccination agent1-3. Acute severe inflammatory processes affect the white matter of the central nervous system. It is difficult to distinguish ADEM from first presentation of multiple sclerosis (MS). On magnetic resonance imaging (MRI)/ acute disseminated encephalomyelitis is characterized by diffuse periventricular confluent symmetrical lesions as in our patient (Figure-1). Acute disseminated encephalomyelitis is rare in adults and is mostly described in pediatric population. Diagnosis is based on clinical features supported by characteristic demyelinating neuro-radiological lesions4. Cerebrospinal fluid examination helps in excluding other differential diagnosis.

The prognosis of ADEM is generally favorable however if not diagnosed and treated promptly fulminant ADEM can be fatal.

Case Report

A 17 years right handed previously healthy male presented to our emergency department at King Abdulaziz Medical City Riyadh with sudden onset of recurrent generalized tonic clonic seizures without gaining consciousness in between seizures. Trachea was intubated and mechanically ventilated. Physical examination showed normal vital signs and was afebrile. Cardiovascular respiratory and abdominal examinations were unremarkable. Neurological examination showed comatosed young man with pupils equal normal size and reactive to light. There was no neck stiffness cranial nerves examination was normal motor examination showed bilateral hyperactive corticospinal tracts with bilateral extensor toes responses. Brain Computer tomography (CT) scan revealed multiple hypo-densities involving both subcortical white matters( not shown). His blood tests showed normal values for complete blood count (CBC) serum electrolytes renal and liver function tests.

The serological testing for common viruses was unremarkable. Cerebrospinal fluid (CSF) examination revealed mild elevation of total proteins (0.47 g/liter) (normal less than 0.45g/liter) with normal white blood count (WBC) and glucose. A diagnosis of ADEM was clinically suspected and patient started on methylprednisolone one gram intravenously daily for five days. Phenytoin loading dose followed by intravenous (IV) maintenance dose and midazolam infusion were administered. MRI brain showed extensive bilateral confluent diffuse hyper-intensities (Figure-1) which supported the clinical diagnosis of ADEM. Seizures were controlled but as there was no clinical response to steroids intravenous immunoglobulin (IVIG) were started in 0.4g/kg body weight daily for five days. There was still no improvement after two weeks in the intensive care unit (ICU) still being intubated and mechanically ventilated. Plasma exchange was started for five sessions on alternative days.

The patient started showing improvement thereaft er; he was extubated and transferred to the ward. He showed gradual improvement and was put on regular physiotherapy and discharged home after three months of hospitalization.

He went back to school however he reported attention deficit disorder and lack of concentration. This was successfully treated by benzhydrylsulphinylacetamide 200 mg orally twice a day. Now patient is a university student with normal cognitive and physical activities and he performed Hajj last year. He is still on piracetam 500mg orally twice a day. MRI brain repeated one year later showed significant improvement with residual white matter changes (Figure-2).

Discussion

We present a young man who developed fulminant ADEM diagnosed by clinical history neurological examination and treatment started in the emergency department few hours after presentation. Brain CT scan and MRI supported the clinical diagnosis. CSF examination and other blood work up helped in excluding other differential diagnosis particularly infectious causes. Acute disseminated encephalomyelitis is a childhood disease. In most cases presentation is gradual over days or weeks and in many cases proceeded by prodromal symtoms4. The case we are discussing is atypical. He presented with sudden onset status epilepticus necessitate tracheal intubation and mechanical ventilation in the ICU. The second atypical feature is resistant to first line immunomodulation therapy of steroids where most of patients with ADEM respond to.

The third atypical character our case is his complete recovery of cognitive and physical function and returning back to school and proceed to university his attention deficit and lack of concentration treated successfully with Provigil which in fact a narcolepsy- cataplexy syndrome treatment. This may encourage double bind placebo control studies of Provigil in patients with attention deficit hyperactive (ADHD) disorder.

These patients with fulminant ADEM are at risk for future overt multiple sclerosis. De Seze J and at el. retrospectively evaluated 60 cases of fulminant ADEM for the risk of future multiple sclerosis and found some differences concerning the risk of evolution to clinically definite multiple sclerosis following the first severe demyelinating attack. Those findings that are atypical for multiple sclerosis include recurrent seizures5 confusion absence of oligoclonal bands in CSF5 and gray matter involvement5. Neuro radiological examination particularly MRI is crucial in the diagnosis6. Thirty percent ADEM patients will have a relapsing-remitting disease similar to multiple sclerosis5 (MS). The diagnosis of ADEM at first neurological presentation is in fact the first attack of MS. Brainstem involvement has a poor prognostic value7. Repeated MRI at least 6 months from onset of neurological presentation should reveal no new lesions in case of ADEM.

Two out of three features (1. Absence of diffuse bilateral lesions 2. Presence of black holes. 3. Presence of two or more periventricular lesions) on MRI may help to differentiate MS from ADEM in children4.

Common precipitating infectious diseases mostly of upper respiratory type (viral bacterial or rickettsial) take 1-2 weeks before having a neurological presentation however this is not a precondition for diagnosis as was seen in the case presented who had no infectious disease. PCR (polymerase chain reaction) is commonly used to support infectious process though it is difficult to prove a causative relationship of ADEM and positive PCR for specific pathogen. Acute hemorrhagic encephalomyelitis is considered as severe variant of ADEM by some experts8. About 25-30% ADEM cases develop into multiple sclerosis5. Treatment of fulminant ADEM depends on the clinical presentation in sub-acute cases methylprednisone one gram IV for 3-5 days with close monitoring of neurological condition is recommended. If the condition deteriorates there is no literature/ guideline to choose between IVIG and plasma exchange.

However other immunosuppressive agents such as cyclophosphamide methotrexate are reportedly used in non-responding cases.

Prognosis of ADEM in the past used to be poor. However due to the decreased incidence of post infectious measles the prognosis has improved by the early diagnosis and use of high dose steroids. Full recovery is expected in 70-90% cases with or without minor neurological deficits like narcolepsy attention deficit and KlA1/4ver-Bucy syndrome9-11. Mortality may reach 5% especially in those having rapid severe onset of disease and extensive brain lesions particularly severe involvement of brain stem. The clinical outcome may be poor if the lesions are extended into white matter 6 or infratentorial structures7. Occurrence of seizure is often associated with a poor outcome12.

Conflict of Interest

All authors declare to have no conflict of interest.

References

1.Tenembaum S Chitnis T Ness J Hahn JS. International Pediatric MS Study Group Neurology. Acute disseminated encephalomyelitis. Neurology 2007;68:S23-36.

2. Garg RK. Acute disseminated encephalomyelitis. Postgrad Med J 2003; 79:11-7.

3. Swamy HS Shankar SK Chandra PS Aroor SR Krishna AS Perumal VG. Neurological complications due to beta- propionolactone (BPL) inactivated antirabies vaccination: Clinical electrophysiological and therapeutic aspects. J Neurol Sci 1984; 63:111-28.

4. Hynson JL Kornberg AJ Coleman LT Shield L Harvey AS Kean MJ. Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 2001; 56:1308-12.

5. De Seze J Debouverie M Zephir H Lebrun C Blanc F Bourg V et al. Acute fulminant demyelinating disease: A descriptive study of 60 patients. Arch Neurol 2007; 64:1426-32.

6. Murthy JM Yangala R Meena AK Jaganmohan Reddy J. Acute disseminated encephalomyelitis: Clinical and MRI Study from South India. J Neurol Sci 1999; 165:133-8.

7.Donmez FY Aslan H Coskun M. Evaluation of possible prognostic factors of fulminant acute disseminated encephalomyelitis (ADEM) on magnetic resonance imaging with fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging. Acta Radiol 2009; 50:334-9.

8. Kuperan S Ostrow P LandiMK. Bakshi R. Acute hemorrhagic leukoencephalitis vs ADEM: FLAIR MRI and neuropathology findings.Neurology 2003; 60: 721-2. 9.Victoria Singh-CurryParesh Malhotra Simon F Farmer Masud Husain Attention deficits following ADEM amelioratedby guanfacine. J Neurol Neurosurg Psychiatry 2011;82:688-690.

10. Jha S1 Ansari MK. Partial KlA1/4ver-Bucy syndrome in a patient with acute disseminated encephalomyelitis. J Clin Neurosci. 2010 Nov;17(11):1436-8.

11. Kuni BJ1 Banwell BL Till C. Cognitive and behavioral outcomes in individuals with a history of acute disseminatedencephalomyelitis(ADEM).Dev Neuropsychol. 2012; 37:682-96.

12. Sonneville R Demeret S Klein I Bouadma L Mourvillier B Audibert J et al. Acute disseminated encephalomyelitis in the intensive care unit: Clinical features and outcome of 20 adults. Intensive Care Med 2008; 34:528-32.

ZCZC

Distribution of Aflatoxins and Micro Organisms in Peanut and Sunflower Seed Products and their Potential Health Hazards

By: Hezron S. Nyandieka1 Henry D. Nyamogoba2 Caleb I. Nyamwange

_: Abstract

Background: Aflatoxins are mould metabolites of Aspargillus flavus and parasiticus that contaminate foodstuffs stored in warm moist places. These toxins are hepatotoxic and produce hepatocellular carcinoma in animals and man.

Objectives: To determine the presence of aflatoxins and microorganisms in ready to consume products of peanuts and sunflower seeds of an edible oil processing factory.

Materials and Methods: Five hundred grams each of peanut kernels peanut pellets sunflower seed pellets peanut oil and sunflower seed oil produced by a local oil extracting factory were supplied for extraction and estimation of aflatoxins and microorganisms like Salmonella Escherichia coli (E.coli) Bacillus and Moulds. Aflatoxins B1 B2 G1 and G2 were extracted in chloroform and concentration was measured using silica gel columns. The quantitative estimation of these aflatoxins B1 B2 G1 and G2 was done by fluorescence evaluation on Thin Layer Chromatograms.

Results: All test samples contained four types of aflatoxins. The highest aflatoxin values were seen in the pellets and lowest in refined oils. All samples contained higher content of aflatoxins B1 and B2 than G1 and G2. Refined peanut oil contained much lower aflatoxin than the sunflower seed oil. This study has also identified the presence of several types of microorganisms such as Salmonella E. coli Bacillus and Moulds in ready to eat peanut and sunflower seed products. Conclusion: Detection of high levels of aflatoxins and microorganisms in ready to eat food stuff should be a concern for food regulatory agencies since these products are consumed daily by the common man and their cumulative effect on the body might be adding to liver cancer in the population.

Policy message: Food regulatory agencies should regularly carry out thorough surveillance on food stuff.

Key words: Aflatoxins microbial counts peanut and sunflower seed products health hazards. Introduction

flatoxins are a group of highly oxygenated mycotoxins produced by fungi Aspergillus flavus and Aspergillus parasiticus which contaminate food crops such as cereal grains oil seeds and peanuts12. Contamination of these commodities occurs in areas where food is produced or stored and where conditions are favorable to mould spoilage and the consequent mycotoxin production3. Hot and humid temperature favors the growth of these moulds4. Common toxins that contaminate foodstuffs include Aflatoxins B1 B2 G1 G2 M1 and M 2. Among these aflatoxin B is the most toxic and carcinogenic in both animals and humans affecting primarily liver5.

Aflatoxins have been implicated in causing liver cancer in Africa and elsewhere and the prevalence of hepatocellular carcinoma has been correlated to the extent of aflatoxin contamination in foodstuffs67. Human exposure to these toxins can be direct or indirect from food crops and animal products such as smoked meats89. Contamination often occurs at pre-harvest during harvest and post harvest period when climatic conditions favor the growth of aflatoxin producing fungi2. The biochemical basis of aflatoxin induced cellular damage and carcinogenicity is thought to be through epoxides activiating cytochrome P450 The epoxides are trapped as aflatoxin DNA-adducts and they constitute a critical step in tumor initiation11. Lipid peroxidation and formation of aflatoxin DNA-adducts are the principal manifestations of aflatoxin-induced liver cell damage512. Moreover aflatoxins have been shown to cause liver cancer in humans7 and in laboratory animals.

Because of the potential health hazards associated with the consumption of aflatoxin contaminated food items this study was carried out to determine the distribution of aflatoxins and microorganisms in edible oil products.

Materials and Methods

The study was carried out at the laboratories of Medical Biochemistry of Moi University School of Medicine and Webuye District Hospital in Kenya. Samples of 500gm each of peanut kernels peanut pellets sunflower seed pellets peanut oil and sunflower-seed oil were supplied by a local Oil Extracting Factory for extraction and estimation of Aflatoxins. About 100gm of peanut kernel was first pounded in a porcelain mortar and then blended in a high speed blender. For each peanut and sunflower-seed pellet thorough mortar-pounding was done before blenderizing it. Subsequent extraction and purification of aflatoxins was carried out by a slightly modified version of method of Epply14 for peanut and oil containingproducts.Thismodificationincluded extraction in chloroform concentration on silica gel columns and quantitative estimation of aflatoxins B1 B2 G1 and G2 by fluorescence evaluation on thin-layer chromatograms (TLC). The sensitivity of this method is equal to 1g/kg (1ppb).

The assay re sults were coded onto IBM cards for statistical analysis with the help of Moi University Computer Centre. The Aflatoxin concentration (g/kg) for peanut and sunflower seed products were analyzed by Microsoft Excel Software 2003 using aflatoxin standards containing 10g/ml (Table-1).

Table 1: Quantitative estimation of aflatoxins in peanut and

sunflower-seed products.###

###Aflatoxin Content per 100g Sample

Sample###N###AFB1###AFB2###AFG1###AFG2

Peanut###100g###5243.5###3763.8###1442.6###1031.5

kernels###

Peanut###100g###8403.0###6503.4###1842.4###1051.5

pellets###

Sunflower###100g###7403.2###5103.5###1642.5###1101.2

seed pellets###

Peanut oil###100g###120.6###100.6###100.6###120.6

Sunflower###100g###240.2###180.4###200.4###180.4

seed oil

Total and differential microbial counts on peanut kernels peanut pellets and sunflower seed pellets were carried out using a slightly modified method of Abalaka and Elegbede3 where microbial counts were carried out on 300 gm samples of peanut kernels peanut pellets and sunflower seed pellets. For all microbial counts 100ml peptone water was added to 100gm sample and the mixture was incubated for 8hrs with occasional shaking. A serial dilution (1/10) of all original samples were carried out in peptone water after every 5-minute to avoid microbial cell injury. 0.1ml sample from each serial dilution was then transferred into three plates. The plates were swirled and incubated at intervals of 250C 300C and 370C for 24hr at each interval. The shifting period was to promote maximum microbial growth. Colonies growing on the plates were counted after 72hr using a colony counter and recorded (Table-2).

Table 2: Microbial counts on samples of peanut and sunflower seed pellets.

Samples###N###Number of Microbial Count for 100g Sample

###Bac-###Moulds+###E.###Salmo-###Total

Peanut###100###412###143###20###13###4x107

kernels

Peanut###100###20###11###5###3###5x103

pellets

Sunflower###100###13###21###4###2###4x102

seed

Results

All samples of peanut and sunflower seed products namely peanut kernels peanut pellets sunflower seed pellets peanut oil and sunflower seed oil contained substantial amounts of Aflatoxins B1 B2 G1 and G2 (Table-1). Highest aflatoxin values were recorded in kernels and pellets while the lowest values were recorded in refined oil products. Both the pellets and the kernels contained high values of aflatoxins B1 and B2 than G1 and G2. Mean values for B1 and B2 were 524g/kg and 376g/kg for kernels respectively. For peanut pellets mean values for B1 and B2 were 840g/kg and 650g/kg respectively. For sunflower seed pellets mean values for B1 and B2 were 740g/kg and 510g/kg respectively. Mean values for peanut oil ranged from 10 to 12g/kg for all Aflatoxins (B1 B2 G1 G2) while for sunflower seed oil the range was between 18 to 24g/kg for all Aflatoxins.

A total of 300gm samples of peanut kernels peanut pellets and sunflower-seed pellets were examined for microbial counts and types of micro organisms. The results of these determinations are shown in Table-2. The kernels contained highest number of Bacillus (412 counts) and moulds (143 counts) while peanut pellets contained lowest number of Salmonella (3 counts) and E.coli (5 counts). In sunflower-seed pellets the lowest microorganism numbers recorded were Salmonella (2 counts) followed by E.coli (4 counts) Bacillus (13 counts) and moulds (21 counts) (Table-2). Generally pellets had low bacterial counts as compared to those for kernels.

Discussion

This study revealed that the peanut and sunflower seed products derived from an edible oil processing factory were contaminated with aflatoxins and micro organisms. The levels of aflatoxin contamination were sufficient to cause major concern to food regulatory agencies and to consumers.

Aflatoxin contamination can occur at any stage from pre-harvest to harvest and post harvest period26. Since these products were purchased by the factory directly from the farmers and stored in the factory's premises before processing therefore contamination probably must have occurred in the factory's storage facility contrary to the views of other similar investigators3 as they have not been able to establish the origin of the contamination3.

Several factors could be responsible for the observed higher levels of aflatoxins in the pellets than in the kernels. It is possible that peanut kernels may have been relatively free of contamination when delivered from the farmers but storage conditions may have caused rapid mould growth and consequent aflatoxin production15. Other possibility is that since pellets represent concentrated form of solid part of nuts and seeds therefore a greater amount of aflatoxins would be pressed into the pellets than then that found in the liquid containing residue after processing. Similar observations have been made by other investigators36.

Presence of substantial amounts of aflatoxins in peanut and sunflower seed oil proves that aflatoxin contamination did not occur on unpelleted products supplied by the farmers. Since these oils are consumed almost on daily basis in many parts of the world therefore presence of aflatoxins in them could have a cumulative effect on the health of consumers. The hepatocarcinogenic and hepatotoxic effect of aflatoxin consumption has been reported by other worker16.

Presence of micro-organisms in peanut and sunflower seed products was not unexpected. Temperature and humidity enhancing aflatoxin production could also have enhanced the growth and proliferation of micro-organisms on stored peanuts and sunflower seeds causing disease in animals and human beings as these micro organisms are known to produce health problems17.

Aflatoxins are cancer causing agents16 and they are easily transmitted to the eggs when consumed by egg laying hens18 therefore their presence in peanut and sunflower seed pellets should be viewed with considerable concern. This is because several feed processing companies use these pellets as raw material for producing a variety of edible oils and feed for egg laying chickens. Since these oils and chicken eggs are consumed daily they could have a cumulative carcinogenic effect on human liver719.

The present study showed the presence of aflatoxins and micro organisms in the products of an edible oil processing factory indicating poor storage in the factory. Since consumers have a high chance of consuming aflatoxin contaminated chicken eggs and edible-oils there is an urgent need to improve the storage and processing of these food products. The food regulatory agencies also need to be more vigilant through regular checking and surveillance to avoid these health hazards.

References

1.Nyandieka HS Maina JO Nyamwange C. Destruction of aflatoxins in contaminated maize samples using ammoniation procedures. East Central Africa J Pharm Sci 2009; 12:47-51.

2. Maitai CK. Distribution of aflatoxin in contaminated maize [Editorial]. East Central Africa J Pharm Sci 2009; 12: 46.

3.Abalaka JA Elegbede JA. Aflatoxin distribution and total microbial counts in an edible-oil extracting plant. Food Chem Toxicol 1982; 20:43-6.

4.Hunter TH. Growth and aflatoxin product in shelled corn by Asperrgillus flavus group and related humidity and temperature [PhD Thesis]. Pardue University 1969.

5.Souza MF Tome AR RAO VS. Inhibition by the bioflavonoid ternatin of aflatoxin B1 induced lipid peroxidation in rat liver. J Pharm Pharmacol 1999; 51:125-9.

6. Safra M Zani F Hashemi S Mahmoud M Khosravi A Shojai-Aliabadi REM. Aflatoxin detoxification using citric acid. Iran J Public Health 2010; 39: 24-9.

7.Alpert ME Hutt MRS Wogan GN. Association between aflatoxin content of food and hepatoma frequency in Uganda. Cancer 1971; 28:253-60.

8.Strzeleki EL. Extraction and determination of Aspergillus flavus metabolites of aflatoxin from meat products. J Int Union Pure Appl Chem 1973; 35:297-307.

9. Gomaa MNE Ayesh AM Abdel Galil MM Khayria N. Effect of high pressure ammoniation procedure on the detoxification of aflatoxins. Mycotoxin Res 1997; 13:23-34.

10. Baertscchi SW Raney KD Stone MP Harris TM. Preparation of 8 9-epoxide of aflatoxin B1 the ultimate carcinogen species. J Am Chem Soc 1988; 110:7929-31.

11. Choy WN. A review of dose response induction of DNA addicts by aflatoxin B1 and its implications to quantitative cancer risk assessment. Mutat Res 1993; 296:181-98.

12. Shen HM Shi CY Lee HP Org CN. Aflatoxin B1 induced lipid peroxidation in rat liver. Toxicol Appl Pharmacol 1994; 127:145-50.

13. Eppley RM. A versatile procedure for assay and preparatory separation of aflatoxins from peanut products. J Ass Office Anal Chem 1966; 49:1218-23.

14. Nyandieka HS Maina JO Nyamwage CI. Detoxification of aflatoxins in artificially contaminated maize crop by ammoniation procedures. Discovery Innovat J 2009; 21:77-79.

15. Jacobson WC Wiseman HG. The transmission of aflatoxin B1 into eggs. Poultry Sci 1974; 53:1743-8.

16. Shank RC Gordon JE Wogan GN Nandasata A Subhamani B. Dietary Aflatoxins and human liver cancer. III. Field Survey of rural Thai families for ingested Aflatoxins. Food Cosmet Toxicol 1972; 10:71-9.

17. Sinell H.J. Food infection communicated from animals to man. In: Hobbs BC Christian JHB Eds. The Microbiological Safety of food. Academic Res Inc. London 1973 pp. 190-240.

18. Newberne PM Butler WH. Effects of Aflatoxin on the liver of domestic and laboratory animals. Cancer Res 1969; 29:236-50.

19. Nyandieka HS Nyamwange CI. The protective effects of flavonoids and vitamin E against liver cell damage caused by aflatoxin B1 in rats. Pak J Med Res 2000; 39: 2-5
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Author:Alayafi, Hassan A.; Jahangiri, Faisal R.; Almuntashri, Mukki
Publication:Pakistan Journal of Medical Research
Article Type:Clinical report
Geographic Code:9PAKI
Date:Sep 30, 2014
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