Creutzfeldt-Jakob Disease (CJD) is a Transient Spongiform Encephalopathy (TSE) that involves degeneration of the central nervous system. The role of prions in the disease is established, although the causal mechanism is still poorly understood .
Organophosphorus compounds are widely disseminated molecules in the environment. Epidemiological studies have suggested an impact of pesticides on the occurrence of some neurodegenerative diseases such as Parkinson's and Alzheimer's .
Research in the literature did not find any article to establish a causal link between organophosphorus and Creutzfeldt Jakob disease.
Authors report one case of Creutzfeldt-Jakob occurring in a context of massive organophosphate poisoning; and they tried through this observation to study any relationship between the two entities.
We are reporting the case of M.C, a 56-years-old man, Farmer without any personal or family medical past, who was highly exposed to organophosphorus for five months and, through intense manipulation of the pesticide; he presented respiratory distress associated with disorder behaviors without seizures that progressively evolved 6 months before his admission. Clinical examination revealed a Glasgow Coma Scale 9/15 associated with myoclonus and 4-limb motor deficit.
The brain MRI showed hyper intensities lesions located at the head of two caudate nuclei and at the level of the diffused cortical evoking a toxic or spongiform encephalopathy (Figure 1).
In this case we discussed the toxic origin more than Spongiform encephalopathy. The standard electroencephalogram showed a slow rhythm of the background with the presence of periodic tri-phasic abnormalities evoking a toxic or spongiform encephalopathy (Figure 2).
And the 14.3.3 protein assay was positive with a slight increase in neopterin which increases the specificity of p14.3.3. Measurement of anticholinesterase activity was 70% (in favor of the intoxication). The study of cerebrospinal fluid revealed cellularity <3 elements; the proteinorrachia at 0.27 g / l and the glucorrachia at 0.67 g /l. Hepatitis B and C, HIV and syphilis serologies were negatives.
Electromyography nerve test was limited, but the values obtained in were normal.
The evolution was marked by the appearance of cognitive disorders with a dementia syndrome and MMS 12/30.
The patient received symptomatic treatment based on rehydration and Piracetam 4800 mg /day with a slight decrease in myoclonus intensity.
Unfortunately, the cessation of exposure to Organophosphate did not regress the symptoms and the patient died after a 7-month.
Through review of the literature, it seems that there is no clear causal link or association between organophosphorus poisoning and Creutzfeldt-Jakob disease.
CJD which is a Transient Spongiform Encephalopathy (TSE) is a degeneration of the central nervous system characterized by the accumulation of a prion. It is characterized by its rarity(incidence 1/1000000) ; its long and asymptomatic incubation phase, its evolution without remission, the absence of a detectable inflammatory or immune reaction and an array of neuropathology associating neuronal loss, spongiosis and astrocytic gliosis .
Four main forms of CJD have been described in the literature: Sporadic CJD (SCJD), genetic CJD, variant CJD (vCJD) and iatrogenic CJD. The CJD sporadic represents 85% of the CJD case, concerns the older adults (median age of 68 years) and has a median survival of 5 months. Familial CJD comprises 10% to 15% of cases and is caused by an autosomal dominant mutation affecting prion protein (PRNP). CJD variant represents less than 1% of cases, generally affects young adults (mean age 29) and presents as a profound psychiatric illness and has been linked to the consumption of food contaminated by the bovine spongiform agent encephalopathy. Iatrogenic CJD accounts for 1% of all cases of CJD, iatrogenic transmission of corneal transplants, surgical equipment, plasma products and human growth hormone [5,6].
The evolution of symptoms and clinical signs is the basis for the diagnosis of sporadic CJD. There are no specific symptoms at the beginning of the disease. Most often a combination of dementia and behavioral/psychiatric symptoms with cerebellar and extrapyramidal signs along with impairment of cognitive functions and behavioral disorders [1,7]. Our patient presented with symptomatology similar to that described in the literature and he had no family history or surgery or administration of a plasma product or human growth hormone so the disease was retained: Creutzfeldt Jakob in its sporadic form.
Hyper intensities in the cerebral cortex and basal ganglia are well-known features of Creutzfeldt-Jakob disease shown on T2-weighted and FLAIR-weighted MRI images as in our patient who found localized hyper intensities lesions at the level of the head of two caudate nuclei and at the diffuse cortical level .The diffusion sequences are useful modalities for the early diagnosis of Creutzfeldt-Jakob disease, in addition to the interest of the diffusion sequence to make the diagnosis. It also has the advantage of being interpretable most of the time, unlike conventional morphological sequences that are frequently artifacted by patient movements. Thalamic involvement should not be neglected in the sporadic form and the measurement of ADC (Apparent Diffusion Coefficient) can help to identify this involvement [8-10].
The main indirect marker of the positive diagnosis of Creutzfeldt Jakob disease is 14-3-3 protein in the CSF with a sensitivity of 92% and a specificity of 80% . The RT-QuIC, which constitutes a direct marker, is a test whose studies have shown that it has sensitivity comparable to the indirect markers of CSF, in particular the 14-3-3 proteins with specificity close to 100% .The RT-QuIC is reserved for some indications , in our case it seems appropriate to carry out this examination, given the atypical context of occurrence but we don’t have this test study in Morocco.
In Morocco, organophosphorus pesticides represent one of the first agents responsible for acute intoxication . Organophosphorus poisoning can be responsible for significant mortality 4, 35 % ; most often related to respiratory impairment which can evolve to Adult’s Respiratory Distress Syndrome (ARDS). Organophosphorus (OP) is a lethal toxicant with predominant systemic action whose main mechanism of action is to block the breakdown of acetylcholine in cholinergic synapses by irreversible inhibition of cholinesterase. The mechanisms of action of OPs on the central nervous system are not limited to the inhibition of central acetyl cholinesterase . Indeed, other neurotransmission systems seem to be involved in the genesis of convulsions caused by OPs; there is probably an imbalance between the excitatory systems (acetylcholine, glutamate) and GABAergic system inhibitors, which explains the triggering of seizures. A delayed neurotoxic syndrome, not related to AChE inhibition can be observed 2 to 5 weeks after acute intoxication by some OPs. It is a predominantly motor-driven distal sensitive-motor neuropathy (paresthesia of the extremities, ataxia and flaccid paralysis of the legs evolving secondarily to spastic hypertonia); behavior problems can occur after chronic or acute poisoning, even minor. They are associated with a significant decrease in plasma and globular cholinesterase. They result in a decline in intellectual performance, with electroencephalographic changes considered by some as specific; CT studies have found aspects of cerebral atrophy but no involvement of the caudate nuclei as described in Creutzfeldt Jakob disease [15-17].
Our patient manifested respiratory distress due to massive exposure of organophosphorus, which motivated hospitalization in intensive care unit for 10 days, he benefited from the symptomatic measures and the dosage of cholinesterase activity was in favor of intoxication.
Cell Prion Protein (PrPc) is a GPI (GPI: Glycosyl Phosphatidyl Inositol)-anchored sialoglycoprotein and consists of five repeats of eight amino acids. The PrPc misfolded gives the Scrapie (PrPSc) form which is the origin of TSEs (encephalopathy spongiform) resulting in cell death by the accumulation of PrPsc in neuronal cells . Various studies were focused on the characterization of the pathological form of PrPsc prion mainly at the neuronal level and it has been shown PrPc-deficient cells are much less viable and more sensitive to oxidative damage than cells that have them, suggesting that PrPc may be involved in the control of oxidative stress . Prion plays a role in inflammatory processes at the neuronal level and also in peripheral tissues in addition to a cytoprotective and anti-apoptotic activity of the Prion. Stress and inflammation have been shown to modulate Prion expression .
Through our observation and review of the literature, it seems that there is no clear causal link or association between organophosphorus poisoning and CJD but a possible relationship that should not be eliminated. Further research and clinical trials would be necessary to evaluate the risk of exposure and the influence of organophosphorus on the folding of prion protein to elucidate the mechanism of a possible effect.
The autopsy is a formal proof to distinguish between the two entities but this procedure is limited by religion and legislative texts in Morocco.
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Availability of data and materials: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Competing interests: The authors declare that they have no competing interests.