Clinical Features and Potential Etiology of Epilepsy and Nodding Syndrome in the Mahenge Area, Ulanga District

NCT03653975 | Unknown

• 1 other identifier: HD-DZIF-MUHAS
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Childhood epilepsy disorders are particular frequent in the area around Mahenge, southern Tanzania and recent studies have described a novel type of epilepsy with repetitive head nodding episodes and often progressive cognitive dysfunction. Despite the disease affecting thousands in Tanzania, Uganda and South Sudan, etiology and pathogenesis of the disorder termed Nodding Syndrome (NS) is still obscure as the phenotype remains imprecisely described. Epidemiological associations with Onchocerca volvulus and Mansonella spp. were noted at different African sites and remain robust even though no evidence for the presence of O. volvulus in CSF or any previous contact with the CSF was found. Hypothesis: With regard to the complex host immune reaction to O. volvulus, the investigators hypothesize that the immune response against filariae might contribute to NS and epilepsy. The investigators further assume that specific genetic traits might play a role in the pathogenesis of NS. Aims In the present study the investigators aim to examine if and how O. volvulus and/or Mansonella spp. contribute to the pathology of NS/epilepsy and therefore intend to analyze the filarial infection and the host immune response in affected children. To identify inherited traits predisposing for epilepsy, NS or specific immune responses, a genetic workup that includes whole-exome sequencing (WES) is performed. The clinical and EEG characteristics are further defined. Cognitive impairment of people with epilepsy and NS is assessed using the Wechsler Nonverbal Scale of Ability (WNV). Study design: A cross-sectional observational (groups I-III) and a case-control (groups I-V) study recruiting in total 250 patients and controls (I: people with NS, n=50; II: people with epilepsy (PWE) and onchocerciasis, n=50; III: PWE without onchocerciasis, n=50; IV: controls with onchocerciasis but otherwise healthy, n= 50; healthy controls without evidence for onchocerciasis, n= 50) is performed to describe the clinical characteristics in children with NS/epilepsy and to evaluate differences in infection and immune response between groups, respectively. The WNV should be validated in 500 healthy controls to obtain reference data in rural Africa. Summary: In summary, the study aims to elucidate clinical characteristics and the pathogenesis of NS/epilepsy in children of southern Tanzania and role of parasitic infection as a cause for NS/epilepsy.

Conditions

Nodding Syndrome; Epilepsy; Onchocerciasis; Cognitive Impairment

Keywords

Nodding Syndrome; Head Nodding; Epilepsy; Onchocerciasis; Cognitive impairment; Mahenge

Outcome Measures

Primary Outcomes (2)

• Describing clinical features in children with Nodding Syndrome and other forms of epilepsy e.g. characteristics of the seizures, EEG abnormalities and reporting co-morbidities and impairments.

  Obtaining clinical features and medical history. Comparing medical history, Seizure types and -frequency and other clinical Features between the groups.

  2014-2018

• Describing EEG features in children with Nodding Syndrome and other forms

  Performing EEG recordings and comparing EEG abnormalities (numbers, types and site of epileptiform discharges (ED), background alterations) between the groups.

  2014-2018

Secondary Outcomes (5)

• Measuring the rate of filarial infections in patients with NS, epilepsy and controls.

  2014-2018

• Characterization of O. volvulus in patients with Nodding Syndrome and epilepsy.

  2014-2018

• Characterization of the host immune response to O. volvulus.

  2014-2018

• Analyzing for genetic traits associated with epilepsy, NS, enhanced Ivermectin toxicity or specific immune responses.

  2014-2018

• Measuring the cognitive impairment in patients with NS and epilepsy.

  2014-2018

Study Arms (6)

Nodding syndrome

I) probable Case of Nodding Syndrom (according to the "WHO epidemiologic surveillance case definition") \*reported head nodding \*\* in a previously healthy person with at least 2 major and 1 minor criteria Major criteria * Age 3 to 18 y at onset of head nodding * Nodding frequency 5 to 20 times per min Minor criteria * Other neurologic abnormalities * Clustering in space or time with similar cases * Triggering by eating or cold weather * Delayed sexual or physical development * Psychiatric manifestations * As agreed upon at the first International Conference on Nodding Syndrome, Kampala, Uganda, July 2012 (16). \*\* Repetitive involuntary drops of the head toward the chest on \>2 occasions.

Other: no intervention

epilepsy and onchocerciasis

II) People with epilepsy (PWE) and onchocerciasis (n= 50) * confirmed or suspected generalized and idiopathic epilepsy * confirmed active infection with O. volvulus (microscopy, PCR and serology) Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention

epilepsy, no onchocerciasis

III) People with epilepsy (PWE) without onchocerciasis (n= 50) * confirmed or suspected generalized and idiopathic epilepsy * excluded active or past infection with O. volvulus (microscopy, PCR and serology) Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention

no epilepsy but onchocerciasis

IV) Controls with onchocerciasis, otherwise healthy (n= 50) * no evidence for epilepsy or other neurological diseases * confirmed active infection with O. volvulus (microscopy, PCR and serology) Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention

no epilepsy, no onchocerciasis

V) Healthy Controls without onchocerciasis (n= 50) * no evidence for epilepsy or other neurological diseases * excluded active or past infection with O. volvulus (microscopy, PCR and serology) Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention

controls for Wechsler Nonverbal (WNV)

Healthy Controls for cognitive assessment only, (n= 750) no evidence for epilepsy or other neurological diseases no detailled examination on O. volvulus performed Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention

Interventions

no intervention OTHER

no intervention

Nodding syndrome; controls for Wechsler Nonverbal (WNV); epilepsy and onchocerciasis; epilepsy, no onchocerciasis; no epilepsy but onchocerciasis; no epilepsy, no onchocerciasis

Eligibility Criteria

• Age: 3 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

With support of the hospital staff, participants aged 3 to 99 years will be recruited consecutively among the registered patients as they are seen once a month for a clinical check-up and to receive their medication. Suitable relatives of patients will also be asked to take part in the study. The study groups with their respective inclusion criteria are defined above. Patients of group I-III will be first recruited into the cross-sectional study and subsequently into the case-control study. Groups II to VI will be matched to Group I for age, gender, social status and stay within the Mahenge area.

You may qualify if:

• Patients of group I-III will be first recruited into the cross-sectional study and subsequently into the case-control study. Groups II to VI will be matched to Group I for age, gender, social status and stay within the Mahenge area.
• exlusion criteria: Patients with evidence for co-infections with HIV, Tb, Malaria or other parasites, cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Sponsors & Collaborators

• Heidelberg University: lead

Study Sites (1)

Mahenge Epilepsy Clinic

Mahenge, Tanzania

RECRUITING

Related Publications (1)

• Arndts K, Kegele J, Massarani AS, Ritter M, Wagner T, Pfarr K, Lammer C, Dormann P, Peisker H, Menche D, Al-Bahra M, Prazeres da Costa C, Schmutzhard E, Matuja W, Hoerauf A, Layland-Heni LE, Winkler AS. Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns. PLoS Negl Trop Dis. 2023 Aug 3;17(8):e0011503. doi: 10.1371/journal.pntd.0011503. eCollection 2023 Aug.

  PMID: 37535695 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

To further describe the clinical features of NS, a complete physical and neurological examination in patients with NS and controls is performed at the Mahenge Epilepsy Clinic. All individuals will have to undergo sampling of blood and skin snips from at least two different areas of the body, one of which must be close to the head. Time expenditure for the individual participant is estimated with 60 min (Introduction of the study, consent, skin snip, lumbar puncture and venipuncture) extended for about 60 minutes if EEG recordings are obtained.

MeSH Terms

Conditions

Nodding Syndrome; Epilepsy; Onchocerciasis; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Thomas Wagner, MD

CONTACT

Wagner.Thomas@rheuma-kinderklinik.de

Thomas Wagner, MD

CONTACT

Thomasiminternet@gmx.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: August 31, 2018
• Study Start: October 1, 2014
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: August 31, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

TA (1)