The Current State of Parkinsonism in West Africa: A Systematic Review

Parkinsonism is one of the most common neurodegenerative diseases among the elderly. Africa is experiencing an increasing burden of age-related conditions including parkinsonism. However, there is not enough data on the prevalence, symptoms, and management of the disorder in West African patients. This systematic review examines the current state of parkinsonism in West Africa by discussing its epidemiology, symptomatology, and treatment. We searched PubMed, BioMed Central, and AJOL databases from January 2000 to December 2020 for studies on parkinsonism conducted in West African countries. We included 32 studies in this review: 23 from Nigeria, 5 from Ghana, and 1 each from Benin, Mali, Niger, and Senegal. Out of the 32 reviewed studies, 11 focused on the prevalence of parkinsonism, 4 examined the genetics of Parkinson's disease (PD), and 17 described the symptomatology and therapy of parkinsonism. The prevalence of parkinsonism in West Africa ranges from 6.0% to 8.3% of neurologic admissions/consultations. The estimated crude prevalence of PD in West Africa varies from 15 to 572 per 100,000 people. Thus far, no pathogenic genetic variants have been associated with PD in the region. Levodopa is frequently used singly or in combination with other medications to manage parkinsonian symptoms, which is consistent with reports from other African regions. Most of the reviewed studies focused only on PD, limiting assessment of other forms of parkinsonism. Almost all the prevalence studies were hospital-based and monocentric, making it impossible to accurately estimate the true prevalence of parkinsonism in West Africa. Larger community-based prevalence studies are recommended to enable accurate quantification of disease burden. Future genetic investigations should consider a wider array of gene mutations associated with parkinsonism. Moreover, public health surveillance strategies should be established to monitor the epidemiology of the disorder.


Introduction
Parkinsonism is one of the most prevalent chronic neurologic syndromes in the elderly and the second most frequent type of movement disorder after essential tremor [1]. It may be idiopathic (Parkinson's disease: PD) or may stem from underlying health conditions-collectively termed secondary parkinsonism (SP). PD, the idiopathic form of parkinsonism, is the fastest-growing neurologic disorder worldwide [2] and affects ∼2% of persons above age 60 [3][4][5].
ere is compelling evidence that mutations at several genetic loci may mediate its development. However, disparities in findings from genetic investigations suggest that the genetics of PD is markedly different among different populations of the world [6]. For example, different variants of the LRRK2 gene-a gene associated with PD risk-have been demonstrated to have distinct distributions in diverse populations [5]. SP may be caused by drugs, cerebrovascular accidents, manganese toxicity, and brain tumours [7][8][9].
Currently, Africa is experiencing rapid transitions with increased life expectancy. ere is an increasing number of people aged 60 or older, and this trend is foreseen to continue [10]. Consequently, the burden of age-related conditions such as parkinsonism may be increasing [11].
Nonetheless, there is a paucity of data on the prevalence, symptoms, and management of parkinsonism disorder in African patients. Given that the disorder may result from several factors, its development may differ within African regions. is poses an important question: "what is the West African situation?" is systematic review summarizes recent studies on parkinsonism in West African countries, in order to appreciate the progress made in understanding the condition as well as emphasize the need for further research on the subject.

Methods
Online databases were systematically searched for articles on parkinsonism in West Africa published from the year 2000 to the year 2020. e databases searched were PubMed, BioMed Central, Embase, Web of Science, ScienceDirect, Scopus, and African Journals Online (AJOL). French databases "La Banque des Données en Santé Publique" (BDSP) and "Institut d'Epidémiologie Neurologique et de Neurologie Tropicale" (IENT) were also searched. Search terminologies used were [Parkinsonism OR "Parkinson's disease" OR "Parkinson disease" OR "Parkinsonian disorder"] AND "West Africa". We also matched the term [Parkinsonism OR "Parkinson's disease" OR "Parkinson disease" OR "Parkinsonian disorder"] with all 16 West African countries to ensure all relevant studies were obtained.
Papers were initially selected based on title and abstracts, taking into account the inclusion and exclusion criteria presented below. ey were then narrowed down after a critical evaluation of their full text. Publications were considered relevant if they presented data on parkinsonism in any West African country, irrespective of the study objective. References of relevant papers were manually scrutinized for publications that may have been missed in the initial search.

Inclusion Criteria.
Original research articles, case reports, and case series on West African parkinsonian patients which were published from 2000 to 2020 formed the inclusion criteria.

Exclusion Criteria.
Conference abstracts, editorials, short communications, systematic reviews, and meta-analyses were excluded. We also excluded publications that provided a general discussion of parkinsonism without presenting empirical data. Articles on neurologic diseases that did not present any data on parkinsonism were excluded. We excluded studies that did not undergo a formal peer-review process.

Data Extraction.
Two reviewers (JTQ and ENM) independently conducted the data extraction from the included studies. Given the rationale of this review, we did not assess any specific outcomes. Notwithstanding, regarding the symptomatology of parkinsonism, we sought for data on primary motor symptoms, secondary motor symptoms, and nonmotor symptoms experiences by West African parkinsonian patients. We extracted information relating to the characteristics of included studies and the results are as follows: (i) e report: author(s), year of publication, study setting, and study period. (ii) Characteristics of participants: sample size, sex, age at study, and age at disease onset. (iii) Study site: single-or multicentre studies and hospital-or community-based studies. (iv) Study design: cross-sectional, descriptive, casecontrol, case study, or case series. (v) Eligibility criteria: criteria used to diagnose parkinsonism. (vi) Summary findings: prevalence and symptoms of parkinsonism, treatment regimens used.
For genetic studies, we extracted data on the genes studied, genetic mutations found, and the analytical methods used to detect mutations. Risk of bias was assessed regarding sample size, single-and multicentre studies, and referral bias.

Results
From the nine databases searched, 29 studies were considered relevant to this review after screening of abstracts and removal of replicates. Of these, 3 articles were excluded due to unavailability of full texts, 1 paper was excluded due to lack of quantitative data, and 7 additional articles were retrieved through reference screening of selected papers, making a total of 32 articles (Figure 1).
Based on the inclusion and exclusion criteria, we obtained papers from Benin, Ghana, Mali, Niger, Nigeria, and Senegal-6 of the 16 West African countries ( Figure 2). Table 1 presents an overview of the analyzed papers. Categorized by year of publication, 8 and 24 articles were published from 2000 to 2010 and from 2011 to 2020, respectively. e majority (23) of the studies were conducted in Nigeria, 5 in Ghana, and 1 each in Benin, Mali, Niger, and Senegal. All of them were conducted in a single country and almost all were monocentric studies (Table 1).

Prevalence of Parkinsonism in West Africa.
Eleven publications described the prevalence of parkinsonism; 7 from Nigeria, 2 from Ghana, and 1 from Benin, and 1 from Niger. e majority were retrospectively conducted with all but one presenting data on the hospital prevalence of parkinsonism and/or PD. e prevalence of parkinsonism and PD varied from 6.0 to 8.3% and 0.4 to 6.9% of neurologic admissions in hospital-based studies, respectively. e only community-based survey reported a 0.09% prevalence of parkinsonism (Table 2).
For this analysis, the crude prevalence of parkinsonism or PD was calculated as the number of cases per 100,000 persons in the total population. e crude prevalence of parkinsonism, as presented in the community-based study was 91 per 100,000 people. e crude prevalence of PD

Studies included in review (n = 32)
Reports assessed for eligibility (n = 7) Reports sought for retrieval (n = 7) Reports sought for retrieval (n = 29) Reports not retrieval (n = 3) Records identified from citation searching (n = 7) Records identified from databases (n = 4,719) Reports excuded due to lack of empirical data (n = 1) Reports assessed for eligibility (n = 26)    Parkinson's Disease 5  6 Parkinson's Disease varied from 15 to 572 per 100,000 people. PD was the most frequent cause of parkinsonism. Furthermore, there was a male preponderance of PD patients, with the ratio of males to females ranging from 1.5 : 1 to 4.5 : 1. e age at clinical onset of disease ranged from 22 to >67 years while the age of patients at study ranged from 50 to >68 years (Table 2). e diagnostic criteria used for the prevalence studies were the presence of at least three of the following: tremor, rigidity, bradykinesia, and postural instability. In general, no publication directly measured predisposing factors to parkinsonism, although 2 studies reported a positive family history in some patients. e most common types of SP described were vascular parkinsonism and drug-induced parkinsonism ( Table 2).

Genetics of PD in West Africa.
Out of the 32 studies reviewed, only 4 focused on the genetics of PD, of which 3 were carried out in Nigeria and 1 in Ghana. All 4 studies examined hospital-based cohorts. One of them focused on sporadic PD cases, 2 focused on both familial and sporadic PD cases, and 1 did not specify (Table 3). A single study screened for pathogenic variants of the ATXN3 and PRKN genes in Nigerian cohorts. Two groups sequenced exons 31 and 41 of the LRRK2 gene for possible mutations, another screened for the p.G2019S mutation in the LRRK2 gene, while the other screened for 12 mutations in the LRRK2 gene including genetic variants classified as pathogenic in Europeans and Asians. No pathogenic variants of the studied genes were identified in any of the studies (Table 3).

Symptomatology and Treatment of Parkinsonism in West
Africa. Seventeen publications studied the symptoms and complications of PD, the effectiveness of treatment regimens used, and the effect of dietary intake on PD treatment.
irteen of these were conducted in Nigeria, 2 in Ghana, 1 in Mali, and 1in Senegal. All papers were hospital-based investigations, 11 were case-control studies, 3 were descriptive studies, 2 were case reports, and 1 was a comparative analysis between two groups of PD patients. ere was a preponderance of male patients in the reviewed studies. e mean age at disease onset was >60 years, whereas the mean age at study was >62 years. e diagnostic criteria used were the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria. None of the surveys described any predisposing factors, although, in one survey, 19 of 91 PD patients had a positive family history of the disease (Table 4). e key motor symptoms of PD-tremor, rigidity, bradykinesia, and postural or gait abnormalities-were reported extensively in most of the reviewed literature. e secondary motor symptoms frequently experienced include freezing of gait, speech disorders, and dysphagia. e common nonmotor symptoms were cognitive and sleep disorders (Table 5). Several treatment regimens were presented in the reviewed studies. Levodopa was commonly used singly or in combination with other drugs. e dopamine agonists used were bromocriptine, pramipexole, and ropinirole whereas the anticholinergics used were trihexyphenidyl and benztropine. Only one group reported the use of an MAO inhibitor, selegiline (Table 6).

Discussion
is review represents a comprehensive summary of research data on parkinsonism in West Africa. e majority of the reviewed publications investigated only PD, and those that provided data on SP did not describe any risk factors. Nonetheless, this analysis provides data on the prevalence, symptoms, and treatment of parkinsonism in West Africa.
As expected, PD was the most diagnosed form of parkinsonism, as observed in other analyses [1]. We only present data on the estimated crude prevalence of PD in Nigeria as it was the only country with adequate data on the  [40]. In 2013, Philip-Ephraim et al. recorded a crude PD prevalence of 572 per 100,000 people in South-Eastern Nigeria in a 2-year retrospective study [29]. Furthermore, Eze and Kalu in 2014 reported a crude PD prevalence of 80 per 100,000 people in South-Eastern Nigeria in a 2-year retrospective study [31]. us, the evidence suggests interregional variations in crude prevalence. Perhaps, estimates will less likely vary if similar methodologies and diagnostic criteria are used [43]. Nonetheless, the data we present were retrospectively collected in monocentric, hospital-based surveys, making it is difficult to accurately quantify the burden of PD within Nigeria. e causes of SP described in the reviewed literature include drugs, cerebrovascular accidents, dementia, and head trauma. e most frequent types of SP were druginduced and vascular parkinsonism, which is similar to the findings of other surveys [44,45]. Drug-induced parkinsonism is the most common cause of SP in older people [1,8] and is associated with the use of drugs that block dopaminergic receptors or deplete dopamine stores such as antipsychotics, antiemetics, and calcium channel blockers [46]. Vascular parkinsonism accounts for 4.4-12% of all parkinsonism cases and is associated with hypertension, stroke, and diabetes mellitus [45].
Although none of the studies assessed predisposing factors for PD, three articles recorded positive family history of PD in a total of 23 patients. e results of the genetic studies demonstrated the absence of mutations in the ATXN3, LRRK2, and PRKN genes amongst West Africans. Mutations in the LRRK2 gene-especially the LRRK2 G2019S mutation-are responsible for significant PD cases among North-African, European, Asian, and Middle-Eastern populations [5,6,47]. PD due to PRKN and ATXN3 mutations has also been described [48,49]. e different results from genetic studies suggest that the genetics of PD is    markedly different in different populations of the world and that the common LRRK2 G2019S mutation is not a frequent cause of PD in West Africa.
In all the reviewed studies, there was a preponderance of male PD patients. is observation is confirmed by previous findings which have shown that PD is more incident in males than in females, with men being at least twofold at greater risk of PD than women [50][51][52][53][54]. is may be attributed to the neuroprotective effect of estrogen demonstrated in females compared to males [54][55][56], or to the higher expression of pathogenic genes in the dopaminergic neurons of the substantia nigra pars compacta of males [50]. Other hypotheses attribute it to nonhormonal gender factors, due to the strong linkage to the X-chromosome observed in several genome-wide studies of PD susceptibility [49,57]. Age is the most important risk factor for parkinsonism [52]. is fact is observed in this analysis where the mean age of disease onset in most studies was ≥60 years. e association between PD and age suggests that its development depends on cumulative exposure to environmental factors, and/or age-dependent biological factors [58]. Accordingly, the factors for PD etiology may be similar irrespective of geographical area or ethnicity. e primary motor symptoms of PD-tremor, rigidity, bradykinesia, and postural or gait abnormalities-were identified in much of the reviewed literature. Some of the studies reported secondary motor symptoms such as micrographia, hypomimia, speech problems, and dysphagia. Additionally, nonmotor symptoms like cognitive disorders, sleep disorders, and gastrointestinal disorders were observed in some studies. Consistent with other studies, levodopa was used in combination with other drugs such as dopamine agonists to manage parkinsonian symptoms. Other drugs mentioned were anticholinergics and monoamine oxidase inhibitors, both of which have been shown to alleviate the symptoms of PD [52]. A recent study by Hamid et al. Parkinson's Disease 13 demonstrated that PD-specific therapies are largely unavailable and unaffordable in most African countries [59]. ere is a need to initiate and drive policies aimed at improving accessibility to treatment.

Strengths and Limitations.
is review, to the best of our knowledge, is the first of its kind on parkinsonism in West Africa. e information presented in this analysis will inform decisions regarding the development of future parkinsonism screening strategies. Although the data we provide is robust due to the systematic method of article evaluation, there are limitations to this study. Firstly, due to a lack of sufficient data, the epidemiology of parkinsonism in other countries apart from Ghana and Nigeria could not be analyzed. Again, most of the surveys were retrospective and focused only on PD. Furthermore, almost all prevalence studies were hospital-based and monocentric, making it impossible to accurately estimate the true prevalence of parkinsonism in West Africa.

Conclusion
Although research on parkinsonism in West Africa has increased over the years, there is still inadequate data on its epidemiology. PD in West Africa occurs more in males and usually begins after age 60. Moreover, a substantial number of patients experience cognitive dysfunction, motor fluctuations, sleep disorders, and reduced pulmonary function. More community-based epidemiological surveys should assess the risk factors of the disease. Moreover, public health surveillance strategies should be established to monitor the epidemiology of the disorder.