Discussion:
In this communication, we reported a case of delayed cerebellar ataxia due to P. falciparum infection with the onset of slurred speech, bilateral tremors affecting both upper limbs, and an unsteady gait during walking. Cerebellar involvement in P. falciparum malaria can occur during the acute stage of fever, as a consequence of cerebral malaria, as a delayed cerebellar ataxia (DCA), or as a side effect of anti-malarial therapy [23 – 28]. This case of DCA that is induced by malaria infection has occurred in a hyper endemic area in central Sudan, Khartoum state. The development of DCA in this case could be mainly attributed to the lack of detecting the malaria infection during the initial presentation of the patient at outpatient clinic. This delay in reaching a final accurate diagnosis is of high risk particularly in settings like Sudan that are endemic with several life-threatening infection like hemorrhagic fevers. Such delay commonly lead to the development of disease severe sequelae and complication such as neurological syndromes including Guillain‐Barre syndrome (GBS) [29] and CA.
Cerebellar ataxia can be caused by many conditions including alcohol misuse, stroke, brain degeneration, multiple sclerosis, drugs, genetic and autoimmune diseases as well as several infectious diseases [23]. Malaria is one of the leading causes for the development of CA [24 - 28]. Malaria in humans is commonly caused by one of five species of plasmodium, and P. falciparum is the species most associated with the development of neurological complications [30].
Acute cerebellar ataxia can be caused by a wide range of infections including viral, bacterial, fungal, and parasitic infections. Interestingly, in our reported patient, there was no clinical or molecular evidence of any infection other than P. falciparum . Co-infection with main viral infections of public health importance in the country with potential involvement in the development of CA were excluded by screening the blood sample serologically and molecularly [31 - 40]. Additionally, in our reported case, hyperpyrexia is unlikely to cause cerebellar ataxia as our patient developed DCA after an afebrile period. Therefore, the development of DCA can be directly attributed to P. falciparum infection. The pathogenesis of DCA due to malaria infection is attributable to an immune mechanisms that include elevated levels of certain cytokines such as Interleukin (IL)-2, IL-6, and tumour necrosis factor alpha (TNF-α), as these cytokines were found in the cerebrospinal fluid of patients with DCA [41].
Therefore, in countries like Sudan that are endemic with malaria and other infectious diseases that are involved in the development of CA, it is very important to investigate patients with cerebellar ataxia for these infections. Early diagnosis and effective case management of patients with infectious diseases is the main strategy to reduce the development and prevalence of CA in the country. Therefore, physicians work in such settings should be vigilant and improve the differential diagnosis of cerebellar ataxia by taking a comprehensive medical and travel histories combined with a complete clinical examination and recommendations for the corresponding laboratory investigation to improve the diagnosis. Furthermore, in countries endemic with several infectious diseases with overlapped clinical manifestation, more investment should be made on improving the diagnostic capacity.
Although malaria is hyper endemic in Sudan with P. falciparum , as the predominant species, yet development of neurological syndromes that are associated with malaria infection including CA are understudied. Therefore, more investment is needed to further study sequelae and severe complications that are associated with endemic diseases. Particularly that, such studies are warrant to generate evidence to inform and guide policymaking and strategic intervention to reduce the health and socioeconomic burden of such preventable health condition.