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Think central nervous system tuberculosis, also in low-risk children: a Danish nationwide survey
Cecilie Paulsrud1, Anja Poulsen1, Nadja Vissing1
1a Department of Pediatrics and Adolescence , Rigshospitalet University of Copenhagen , Copenhagen , Denmark.
Insights
Pediatric central nervous system tuberculosis (CNS TB) requires prompt diagnosis. In Denmark, children from non-TB endemic countries faced diagnostic delays, highlighting the need for improved detection strategies for CNS TB in low-incidence regions.
Area of Science:
- Neurology
- Infectious Diseases
- Pediatrics
Background:
- Pediatric central nervous system tuberculosis (CNS TB) carries a high risk of mortality and long-term neurological deficits, especially with delayed diagnosis.
- Children from non-endemic countries are particularly vulnerable to delayed or missed CNS TB diagnoses.
- Denmark, a country with low tuberculosis (TB) endemicity and no universal Bacillus Calmette-Guerin (BCG) vaccination, presents a unique setting to study CNS TB in children.
Purpose of the Study:
- To investigate the epidemiology, clinical presentation, diagnostic methods, treatment, and outcomes of pediatric CNS TB in Denmark.
- To identify risk factors for delayed diagnosis in children from both endemic and non-endemic countries.
Main Methods:
- A nationwide retrospective case survey was conducted from 2000 to 2015.
- Data were collected from the National Danish TB Notification Register, including patient demographics, clinical and paraclinical findings, diagnostic imaging, treatment details, and outcomes.
- Epidemiological, clinical, and diagnostic data were analyzed to assess diagnostic sensitivity and treatment timeliness.
Main Results:
- Nine ethnic Danish children and 12 children from TB-endemic countries were diagnosed with CNS TB.
- Standard clinical symptoms, C-reactive protein levels, chest X-rays, and indirect TB screening assays showed low diagnostic sensitivity (19-75%).
- Cerebrospinal fluid (CSF) analysis revealed elevated white blood cells in all patients, with 88% showing characteristic findings (lymphocyte predominance, elevated protein, or hypoglycorrhachia). Cerebral MRI demonstrated abnormalities in 86% of cases.
Conclusions:
- Children from non-TB endemic countries may experience delayed diagnosis and potentially worse prognoses for CNS TB compared to those from high-risk populations.
- Cerebral magnetic resonance imaging (MRI) and characteristic cerebrospinal fluid (CSF) findings are highly sensitive diagnostic tools for pediatric CNS TB.
- Timely diagnosis and treatment are crucial to improve outcomes for pediatric CNS TB, particularly in low-endemic settings.
Background:
Paediatric central nervous system (CNS) tuberculosis (TB) imposes a high risk of death and neurologic sequelae, particularly if the diagnosis is delayed. Children from non-TB endemic countries are particularly at risk of delayed or missed diagnosis. We aimed to investigate CNS TB in Denmark, a TB low-endemic country and where Bacillus Calmette-Guerin (BCG) vaccination is not a part of the vaccination schedule.
Methods:
A nationwide retrospective case survey of all children with CNS TB in 2000-2015 identified through the National Danish TB Notification Register. We assessed epidemiology, clinical and paraclinical features, diagnostic criteria, treatment and outcome.
Results:
Nine ethnic Danes and 12 children from TB-endemic countries with CNS TB were identified. Clinical features, C-reactive protein, chest X-ray and indirect TB screening assays all had low sensitivity (19-75%). All (18/18) patients had elevated cerebrospinal fluid (CSF) white blood cells and 15 of 17 (88%) had a combination of at least two characteristic CSF findings (lymphocyte predominance, elevated protein and/or hypoglycorrhachia). Cerebral computed tomography and magnetic resonance imaging were abnormal in 10 of 16 (63%) and 12 of 14 (86%), respectively. Treatment was initiated after a median of 3 days in children from TB-endemic countries, and after 10 days in ethnic Danish children. One patient died (5%): A native Danish girl who died before the diagnosis was established.
Conclusions:
Children from non-TB endemic countries may be at risk of delayed diagnosis and poorer prognosis compared to high-risk children. Cerebral magnetic resonance imaging and characteristic CSF findings had high diagnostic sensitivity.
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