Nodding syndrome research revisited

Vieri, Melissa Krizia; Hendy, Adam; Mokili, John L.; Colebunders, Robert

doi:10.1016/j.ijid.2021.02.006

Cited by 8 publications

(7 citation statements)

References 27 publications

(35 reference statements)

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“…NS is a devastating childhood neurological disorder, which is characterized by pathological nodding seizures and multiple additional brain pathologies [ 2 , 3 , 4 , 8 , 9 , 21 ]. The affected children experience a complete and permanent stunting of growth and mental handicap [ 2 , 3 , 4 , 7 , 8 ]. While NS is still enigmatic, it is strongly associated with the parasitic worm OV [ 1 , 5 , 8 , 9 , 15 , 16 , 17 , 18 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…The affected children experience a complete and permanent stunting of growth and mental handicap [ 2 , 3 , 4 , 7 , 8 ]. While NS is still enigmatic, it is strongly associated with the parasitic worm OV [ 1 , 5 , 8 , 9 , 15 , 16 , 17 , 18 , 53 ]. Recently, it was shown that autoimmunity might drive the pathology of this disease [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nodding syndrome (NS) is an epileptic disease that affects children within the age range of 3 to 15 years. NS is characterized by severe attacks of head nodding, progressive cognitive dysfunction, neurological deterioration, stunted growth and additional pathological neurological features [1][2][3][4][5][6][7][8]. Many of the NS patients also have frequent episodes of another type of seizures: Generalized Clonic Tonic Seizures (GCTS) [7,9].…”

Section: Introductionmentioning

confidence: 99%

“…Various studies described several etiological factors that might contribute to the onset of this syndrome [ 2 , 3 , 10 , 11 , 12 , 13 ]. The most compelling data point to the association of NS with infection by the parasitic worm Onchocerca Volvulus (OV), transmitted to humans by female blackflies [ 1 , 5 , 8 , 9 , 14 , 15 , 16 , 17 ]. NS was documented mainly in South Sudan, Uganda, and Tanzania.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, Ov infection might induce a broad spectrum of pathologies, termed together Onchocerciasis. Among these Ov-associated pathologies are epileptic seizures, and this kind of epilepsy has been termed Onchocerciasis Associated Epilepsy (OAE) [ 8 , 9 , 15 , 18 , 19 ]. Yet, there is still only limited evidence that the parasite itself invades the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage migration inhibitory factor in Nodding syndrome

et al. 2021

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Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)–a parasitic worm transmitted to human by blackflies. NS seems to be an ’Autoimmune Epilepsy’ in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a −794 CATT5–8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF -173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS.Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expression MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy.

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