MRI Signal Abnormalities of the Optic Tracts, a Marker of Meningoencephalitis Caused by Trypanosoma Gambiense (TG)—A Delayed Patho-Radlological Correlation

Parasitic meningoencephalitis presents several etiologies which sometimes depend on their geographical location. They require thorough blood and ce-rebrospinal fluid check-up for directing an efficient treatment. Clinicians and radiologists are constantly looking for specific signs that could point to a par-ticular etiology. The meningoencephalitis caused by Human African Trypanosomiasis (HAT) due to Trypanosoma brucei gambiense (TG) is a rare disease characterized by a slow progression, over years sometimes. Its non-spe-cific presentation either clinically or in imaging can lead to misdiagnosis and thus, delay the treatment. However, involvement of the optic tracts seems to be characteristic of this condition, on old data from animal experimenta-tion and recent high-field MRI data. MRI is the best current technique to explore the brain, cranial nerves, and visual pathways. In this article, we are going to present two observations of meningoencephalitis caused by HAT and then discuss some specific aspects of this neglected and re-emerging disease. Signal Abnormalities of the Optic Tracts, a Marker of Meningoencephalitis Caused by Trypanosoma Gambiense (TG)—A Delayed Patho-Radlological


Introduction
HAT is a specific African parasitic disease caused by two flagellated protozoans.
They are transmitted to human beings through the tsetse fly bites. The African continent over latitudes 15˚ north and 20˚ south offers ideal conditions for the development of this fly. Trypanosoma brucei gambiense (TG) is found in West and Central Africa while Trypanosoma brucei rhodesiense (TR) is found in East and South Africa (Figure 1). HAT due to TG progresses slowly, over years in some situations and represents almost 98% of all HAT cases. The disease follows two stages: the hemolymphatic stage and the late encephalic stage when the cerebrospinal fluid and the brain are involved. During this latest stage, sleep disturbances appear, hence the name "sleeping sickness".
The eradication program of the WHO is bearing fruit, as a result from 1998 to 2008, the number of cases fell from more than 25,000 to more than 10,000 [1] [2]. The conclusive diagnosis is based on the detection of the parasite in the blood or the CSF and the presence of antiparasitic antibodies in the blood.
For this disease, medical imaging is non-specific and mainly shows signs of encephalitis in the meningoencephalitis stage [3]. The availability of neuroimaging tools leads to the exploration of patients suffering from meningoencephalitis. Its cause must be investigated for optimal treatment. Also, drug administration during the treatment such as melarsoprol in the meningoencephalitis stage is not without risk, linked to fatal arsenical encephalitis in 5% [2].
Few experimental data are available on HAT due to TG. They were carried out by Bogaert in 1962 on cats in a period prior to the invention of the scanner and MRI tools [4] [5].
In this article, we are going to present two observations of HAT at the meningoencephalitis stage investigated on MRI and discuss some aspects of this disease and the correlation with the histopathological data.    )). Involvement of the optic tracts predominantly the right one that appear enlarged and hypersignal (arrowhead in (C)).

Cases Presentation
-Diagnostic Encephalic form (stage 2) of human African trypanosomiasis with associated optic tracts involvement.

Observation 2
Mr. M.K, 45 years old, in the emergency room presented an alteration of consciousness associated with a tremor, abnormal somnolence without fever. A prior high field MRI check-up was done with the same protocol. Blood and cerebrospinal fluid identified evidence of trypanosomiasis.
-MRI findings MRI showed a diffuse vasogenic edema in the grei nuclei and the white matter with a hypersignal in T2 sequences without gadolinium enhancement. Inflammatory signs with a hypersignal in T2 SE sequence and a slight enlargement of the optic tracts were noted (Figure 3).  -Diagnostic Encephalic form (stage 2) of human African trypanosomiasis with associated optic tracts involvement.

Focus Current Point of This Condition
The sleeping sickness is caused by 2 parasites; Trypanosoma brucei gambiense (TG) found in West and Central Africa and Trypanosoma brucei rhodesiense (TR) which occurs in Eastern and Southern Africa (  [6]. Its diagnosis and treatment require a special care system.

Disease History
HAT due to TG is thus a geographic anthropozoonosis disease that occurs in West and Central Africa [1] [6]. The parasite Trypanosoma brucei gambiense (TG); so named because of its discovery along the Gambia River, was first discovered by

Course of HAT Caused by TG
The disease operates in stages after the biting of the tsetse fly and leads to sleeping disturbances which characterizes this so-called "sleeping-sickness" [3] [6] [7] [10]. There was no imaging data in this study.
These data are important and should be taken into account when exploring the optic pathways if encephalitis is suspected, in geographic areas where the vector is present, or when dealing with patients who have travelled in endemic areas.

Imaging of HAT and Correlation with Histopathological Animal Data
High field MRI is the most efficient current technique to explore the nervous system, especially the cranial nerves or optic pathways. Neuroimaging in HAT may be normal or show signs of encephalitis with diffuse vasogenic edema, without hemorrhage or significant contrast enhancement (Figure 2(A), Figure 2(B), Figure 3(A) and Figure 3(B)) in the white matter of the cerebrum and the brainstem, the basal ganglia. This aspect is correlated with Mott's observations (1899). Inflammatory involvement of the optic tracts appears to be characteristic with enlargement, hyperintensity on T2SE and T2 FLAIR sequences and without contrast enhancement (Figure 2(C) and Figure 3(C)) [3] [7]. Correlation with Bo-gaert's experimental animal study confirms that this optic tract damage could be a specific sign of meningoencephalitis due to TG [5].
These MRI findings appear to be the first to be correlated with the neuro-experimental data of Mott and Bogaert studies. Therefore, special attention must be paid to the optic tracts, particularly in case of suspected encephalitis in an endemic area or in patients who travelled in it. Conversely, in the event of an incidental discovery, the process of searching trypanosoma in the blood or in cerebrospinal fluid can be launched.
MRI could be integrated into the management process for patients who suffered from HAT. It makes it possible to follow the signal of evolving lesions but also to differentiate melarsoprol-induced encephalitis (arsenical derivative) from those linked to the parasite [2] [7]. In the sense that, arsenical encephalitis causes hemorrhagic lesions while encephalitis THA does not cause hemorrhage.
The article reported by Ugoji is interesting and reassuring with regard to pregnant women. After two years of follow-up, recovery was obtained without sequelae [11].

Trypanotolerance
For many years HAT was considered fatal if untreated but there is growing evidence that some patients affected by TG remain asymptomatic and may self-cure.

Conclusion
These MRI descriptions on the optic tracts and the encephalitis signs due to TG are in perfect correlation with the animal experimental data carried out by Bogaert in 1962 and Mott's observations in 1899. They seem to be the first described in the reviewed literature. This slowly evolving disease seems to be able to be eradicated. However, vigilance must be constant and MRI must be integrated as a tool for detecting brain damage induced by HAT and as a means of monitoring patients under treatment. This so-called "neglected tropical disease" implies special attention in the WHO eradication program.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this paper.