Ronald van Toorn

• MBChB MRCP FCP PhD
• Pediatric Neurologist at Stellenbosch University

Tuberculous meningitis (TBM) is a very severe form of childhood tuberculosis (TB), requiring hospitalisation for diagnosis. We investigated trends in admission, disease spectrum, outcomes, and healthcare system factors in children with TBM managed at a tertiary referral hospital in Cape Town, South Africa. We conducted a retrospective cohort study...

Aim: To identify cerebral palsy (CP) variables collected in CP registries from high-income countries (HICs) and low-and middle-income countries (LMICs) to assist with the development of a regional CP registry relevant to the African region. Method: A systematic search of online databases to identify peer-reviewed publications and grey literature ab...

Background: Cerebral white matter lesion (WML) formation in people with multiple sclerosis (pwMS) is linked to the death of myelin-producing oligodendrocytes. Current MS treatment strategies focus on limiting WML accumulation and disability. Using a pathology-supported genetic testing (PSGT) program, we identified specific risk factors for MS, cate...

Background Population-based data show high proportions of severe cases of cerebral palsy (CP) in resource-poor regions such as sub-Saharan Africa, where most children have potentially preventable risk factors (factors that may increase the likelihood of CP occurrence but can be mitigated through medical interventions). Objectives This study aimed...

Background: Population-based data show high proportions of severe cases of cerebral palsy (CP) in resource-poor regions such as sub-Saharan Africa, where most children have potentially preventable risk factors (factors that may increase the likelihood of CP occurrence but can be mitigated through medical interventions). Objectives: This study aimed...

Next generation sequencing (NGS)-based tests have become routine first-line investigative modalities in paediatric neurology clinics in many high-income countries (HICs). Studies from these countries show that these tests are both cost-effective and reliable in diagnosing many complex childhood neurological diseases. However, NGS-based testing in l...

Background: Cerebral white matter lesions (WMLs) in people with multiple sclerosis (pwMS) are associated with the death of myelin-producing oligodendrocytes. MS treatment strategies aim to limit WML accumulation and disability progression. It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenes...

Aim To identify cerebral palsy (CP) variables collected in CP registries from high‐income countries (HICs) and low‐ and middle‐income countries (LMICs) to assist with the development of a regional CP registry relevant to the African region. Method A systematic search of online databases to identify peer‐reviewed publications and grey literature ab...

Bhorat et al.[1] have provided a self-styled ‘position statement’ on BGT injury. In doing so, they have uncritically referenced literature and inappropriately used it as the inferential basis for their views, which are unashamedly offered to preferentially assist in the defence of allegations of medical negligence, to which cause they have allied t...

Next generation sequencing (NGS)-based tests have become routine first-line investigative modalities in paediatric neurology clinics in many high-income countries (HICs). Studies from these countries show that these tests are both cost-effective and reliable in diagnosing many complex childhood neurological diseases; however, NGS-based testing in l...

Background: Lipid metabolism may impact disability in people with multiple sclerosis (pwMS). Methods: Fifty-one pwMS entered an ultrasound and MRI study, of whom 19 had followed a pathology-supported genetic testing program for more than 10 years (pwMS-ON). Genetic variation, blood biochemistry, vascular blood flow velocities, diet and exercise wer...

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these iss...

Aicardi-Goutières syndrome (AGS) refers to a group of genetic diseases characterised by severe inflammatory encephalopathy that usually present within the first year of life, resulting in progressive loss of cognition, spasticity, dystonia and motor disability. Pathogenic variants in the adenosine deaminase acting on RNA ( Adar ) enzyme have been l...

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typicall...

Background Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. Methods We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Afr...

BACKGROUND: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. METHODS: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Af...

Aim To better understand the aetiologies of epileptic spasms in infants, as well as the safety and efficacy of high dose corticosteroids in tuberculosis and human immunodeficiency virus (HIV) endemic resource‐limited settings. Method This was a retrospective analysis of infants with epileptic spasms managed at the tertiary referral centres in the...

Objectives The developmental and epileptic encephalopathies (DEE) are a heterogeneous group of rare neurodevelopmental disorders, characterised by early-onset seizures that are often intractable, electroencephalographic abnormalities, and developmental delay or regression. There is a paucity of data from sub-Saharan Africa on the genetic basis of D...

We describe a case of unilateral phrenic nerve palsy due to SARS‐COV‐2 in a young child, which led to prolonged and complicated ventilation. The child was treated with methylprednisolone and IVIG, which led to a complete recovery of phrenic function. Temporary involvement of the phrenic nerve should be considered in children infected with SARS‐COV‐...

Background and purpose: Considerable overlap exists in the MR imaging features of hypoglycemic injury and hypoxic-ischemic brain injury, with similar predilections for the occipital and parietal lobes. In partial, prolonged hypoxia-ischemia, there is cortical destruction at the interarterial watershed zones, and in concomitant hypoglycemia and hyp...

We describe a case of unilateral phrenic nerve palsy due to SARS-COV-2 in a young child, which led to prolonged and complicated ventilation. The child was treated with methylprednisolone and IVIG, which led to a complete recovery of phrenic function. Temporary involvement of the phrenic nerve should be considered in children infected with SARS-COV-...

We present an 11-year-old girl who manifested with unprovoked right-sided focal motor seizures. CT revealed a large lobulated hypodense mass in the left temporoparietal lobe, with perilesional oedema and postcontrast peripheral enhancement. Diagnostic uncertainty resulted in further neuroimaging, which included MRI with modalities including diffusi...

Background: Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown. Methods: To inform a WHO g...

Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB) that arises when a caseating meningeal granuloma discharges its contents into the subarachnoid space. It accounts for ~1% of all disease caused by Mycobacterium tuberculosis and the age of peak incidence is from 2–4 years. The exact pathogenesis of TBM is still...

Introduction: Hyponatremia and/or hypoglycorrhachia are commonly encountered biochemical derangements during the acute stage of childhood tuberculous meningitis (TBM). Few studies have explored the correlation between these derangements and the staging of TBM disease (severity), or explored their role as biomarkers for vascular ischemic events, hyd...

Much of the morbidity and mortality caused by tuberculous meningitis (TBM) is mediated by a dysregulated immune response. Effective host-directed therapy is therefore critical to improve survival and clinical outcomes. Currently only one host-directed therapy (HDT), corticosteroids, is proven to improve mortality. However, there is no evidence that...

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including...

Purpose Cerebrovascular complications are commonly observed in children with tuberculous meningitis. We aimed to determine which clinical factors were associated with stroke at admission in children with tuberculous meningitis and, in children stroke-free at admission, which factors were associated with development of stroke on treatment. Methods...

We report on a unique case of a 7-year-old girl with new onset ocular myasthenia gravis shortly after recovery from multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2 infection. The diagnosis of myasthenia gravis was based on suggestive symptoms of fatigable bilateral orbital ptosis, diplopia, positive ocula...

A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidit...

Syringomyelia associated with tuberculous meningitis (TBM) is an extremely rare condition. Only a few adult cases have been reported. A 12-year-old woman, who previously suffered TBM at the age of 6 months, presented with a long-standing history of right upper limb panhypertrophy, dissociate anaesthesia, frequent headaches, scoliosis and acquired m...

Medical malpractice and cerebral palsy

A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidit...

Objective Human cases of acute profound hypoxic-ischemic (HI) injury (HII), in which the insult duration timed with precision had been identified, remains rare, and there is often uncertainty of the prior state of fetal health. Study Design A retrospective analysis of 10 medicolegal cases of neonatal encephalopathy-cerebral palsy survivors who sust...

Background Much of the neurological sequelae of central nervous system (CNS) tuberculosis (TB) is due to an excessive cytokine-driven host-inflammatory response. Adjunctive corticosteroids, which reduce cytokine production and thus dampens the inflammation, improve overall survival but do not prevent morbidity. This has prompted investigation of mo...

This data article presents datasets associated with the research article entitled “The immunological architecture of granulomatous inflammation in central nervous system tuberculosis’’ (Zaharie et al., 2020). The morphology of tuberculosis related granulomas within the central nervous system of human patients was visualized in six different three-d...

Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate up to 60%. Our aim is to fill the ‘key gap’ in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necr...

Aim To describe the trajectory of clinical signs in children who developed human immunodeficiency virus encephalopathy (HIVE) after starting early antiretroviral therapy (ART). Method This was a retrospective case‐cohort description of HIVE among Cape Town participants from the Children with HIV Early AntiRetroviral treatment (CHER) trial. Criteri...

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment r...

Aims To describe stroke syndromes and transcranial Doppler (TCD) findings in children with human immunodeficiency virus (HIV) and examine the associations between TCD and clinical and laboratory data. Method We enrolled 42 children (24 males, 18 females) with HIV (median age=7y 6mo; 2y 7mo–15y 6mo), with and without stroke who underwent a TCD exam...

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment r...

The assessment and management of tuberculous meningitis (TBM) is often complex, yet no standardised approach exists, and evidence for the clinical care of patients, including those with critical illness, is limited. The roles of proformas and checklists are increasing in medicine; proformas provide a framework for a thorough approach to patient car...

Hyponatremia is the commonest electrolyte abnormality in hospitalized patients and is associated with poor outcome. Hyponatremia is categorized on the basis of serum sodium into severe (< 120 mEq/L), moderate (120-129 mEq/L) and mild (130-134mEq/L) groups. Serum sodium has an important role in maintaining serum osmolality, which is maintained by th...

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), accounting for around 1-5% of the global TB caseload, with mortality of approximately 20% in children and up to 60% in persons co-infected with human immunodeficiency virus even in those treated. Relatively few centres of excellence in TBM research exist and th...

Tuberculous meningitis is the most severe form of tuberculosis and causes widespread mortality and morbidity. Understanding of the epidemiology and pathogenesis is incomplete, and the optimal diagnosis and treatment are poorly defined. To generate research collaboration and coordination, as well as to promote sharing of ideas and advocacy efforts,...

Tuberculous meningitis (TBM) results from dissemination of M. tuberculosis to the cerebrospinal fluid (CSF) and meninges. Ischaemia, hydrocephalus and raised intracranial pressure frequently result, leading to extensive brain injury and neurodisability. The global burden of TBM is unclear and it is likely that many cases are undiagnosed, with many...

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment r...

The assessment and management of tuberculous meningitis (TBM) is often complex, yet no standardised approach exists, and evidence for the clinical care of patients, including those with critical illness, is limited. The roles of proformas and checklists are increasing in medicine; proformas provide a framework for a thorough approach to patient car...

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment r...

Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis of such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment r...

Tuberculous meningitis (TBM) is the most severe form of TB with high rates of mortality and morbidity. Here we conduct RNA-sequencing on whole blood as well as on ventricular and lumbar cerebrospinal fluid (CSF) of pediatric patients treated for TBM. Differential transcript expression of TBM cases are compared with healthy controls in whole blood a...

The human immunodeficiency virus (HIV) epidemic seems largely controlled by anti-retroviral treatment with resultant large numbers of children growing up with the disease on long-term treatment, placing them at higher risk to develop HIV-related brain injury, ongoing cognitive impairment and treatment-related neurological complications. Cerebral wh...

Background: Multiple sclerosis is a disorder related to demyelination of axons. Iron is an essential cofactor in myelin synthesis. Previously, we described two children (males of mixed ancestry) with relapsing-remitting multiple sclerosis (RRMS) where long-term remission was achieved by regular iron supplementation. A genetic defect in iron metabo...

Setting: Cape Town, South Africa, 2014. Objective: To assess the societal costs and cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis. Design: This was an economic evaluation from a societal perspective using probabilistic analysis. Health care, informal care, lost productivity costs and costs in o...

Objectives To evaluate a paediatric treatment‐support intervention for home‐based treatment of HIV infection or tuberculous meningitis (TBM). Methods A randomized‐controlled study comparing local standard care (controls) with standard care plus intervention (combining adherence education, reinforcement and monitoring) in children aged 0‐14 years....

As early diagnosis of childhood tuberculous meningitis cannot rely on mycobacterial confirmation, clinical, cerebrospinal fluid and neuroimaging features are essential. We aimed to describe the evolution of serially analyzed lumbar cerebrospinal fluid parameters. We performed a retrospective observational study including children <13 years with sus...

We describe four CHER (Children with HIV Early antiRetroviral therapy) trial participants with late-onset HIV encephalopathy despite long-standing viral suppression in blood and undetectable HIV DNA and RNA PCR in cerebrospinal fluid. Extensive investigations revealed no alternative etiology. Reassuringly, all four experienced slow spontaneous reco...

Tuberculous meningitis (TBM) remains a major cause of death and disability in tuberculosis-endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the cond...

BACKGROUND: The diagnosis of tuberculous meningitis (TBM) in children is often delayed, with disastrous consequences. The Integrated Management of Childhood Illness (IMCI) strategy aims to ensure the accurate assessment of ill children using simple yet reliable clinical signs. METHODS : We conducted a retrospective observational study of 30 consecu...

Abstract The clinical expression of bilirubin-induced neurological dysfunction varies according to severity and location of the disease. Definitions have been proposed to describe different bilirubin-induced neurological dysfunction subtypes. Our objective was to describe the severity and clinico-radiological-neurophysiological correlation in 30 co...

in that the child contracted measles during the 2009 - 2011 epidemic, during the vulnerable period of infancy before her 9-month measles immunisation. While she was 2 years older at presentation than our previous cases, this is more in keeping with the internationally reported cases’ presenting age of 5 17 years. [2]

Fluoroquinolones are a key component of multidrug-resistant tuberculosis treatment. We describe the first reported case of probable levofloxacin-associated intracranial hypertension in a 6-year-old girl with pulmonary multidrug-resistant tuberculosis. The case highlights the potential risk of secondary intracranial hypertension in multidrug-resista...

A national multicenter study identified 17 South African children with vertically acquired HIV-1 infection and HIV-associated vasculopathy. Five of the children (all indigenous African ancestry) had progressive vascular disease, consistent with moyamoya syndrome. Median presentation age 5.8 years (range 2.2-11). The children with moyamoya syndrome...

In contrast to malaria, multiple sclerosis (MS) is infrequently found in Black Africans. We describe a 29 year old Nigerian female who developed an MS-like condition with symptoms similar to relapsing-remitting MS following malaria infection, leading to a diagnosis of MS. However, absence of hyperintense lesions in the brain and spinal cord present...

Tuberculous meningitis is the most severe form of tuberculosis in children and accounts for a sizable proportion of the mortality caused by the disease. It occurs in 1–3% of children with untreated tuberculosis infection, but accounts for up to 10% of tuberculosis in children less than a year old. The clinical presentation is dictated by the pathol...

p> List of Abstract Titles and authors: 1. Psychosis: A matter of mental effort? M Borg, Y Y van der Zee, J H Hsieh, H Temmingh, D J Stein, F M Howells 2.In search of an affordable, effective post-discharge intervention: A randomised control trial assessing the influence of a telephone-based intervention on readmissions for patients with severe...

Neurologic tuberculous pseudoabscesses that clinically progress despite conventional antituberculosis therapy may be responsive to adjuvant thalidomide, a potent tumor necrosis factor-α inhibitor. In this study, the addition of thalidomide provided substantial clinical benefit in the majority of patients, and magnetic resonance imaging evolution of...

A unique look into human central nervous system granuloma formation identifying three distinct types of granuloma’s: non-necrotising, necrotising gumma, necrotising psudo-abscess. Patients presenting with advanced stage TBM show predominance of necrotizing/reticulin negative granuloma (pseudo-abscess) in the leptomeningis. Direct meningeal involvem...

We investigated familial and environmental risk factors in a cohort of South African children diagnosed with attention-deficit hyperactivity disorder (ADHD). A prospective, hospital-based case control study was conducted comprising 50 children diagnosed with ADHD and 50 matched non-ADHD controls. The adjusted effect of familial-environmental risk f...

The World Health Organization recommends 12-months treatment (2RHZE/10RH) for children with tuberculous meningitis (TBM). Studies evaluating length of antituberculous treatment for TBM report similar completion and relapse rates comparing 6-months treatment with 12-months treatment. A prospective evaluation to determine whether short course intensi...

Transcranial Doppler imaging (TCDI) is potentially a valuable investigational tool in children with tuberculous meningitis (TBM), a condition often complicated by pathology relevant to Doppler imaging such as raised intracranial pressure (ICP) and cerebral vasculopathies. Serial TCDI was performed on 20 TBM children with the aim of investigating ce...

The natural history and manifestation of HIV-related neurological disease have been ameliorated by combination antiretroviral therapy (ART). We describe the characteristics of white matter signal abnormalities (WMSA) on magnetic resonance imaging (MRI) in children with HIV-related neurological disease. We reviewed MRI scans of children with suspect...

Tuberculous meningitis (TBM), the most devastating manifestation of tuberculosis, is often missed or overlooked because of nonspecific symptoms and difficulties in diagnosis. It continues to be an important cause of neurologic handicap in resource-poor countries. Owing to the suboptimal performance of diagnostic tests of TBM, diagnosis relies on th...

BACKGROUND: Little has been published on autism in Africa, and it is not known whether South African children present with the same characteristics and challenges as described internationally. OBJECTIVES: To describe the demographics, history, clinical features, co-morbidity and yield of aetiological investigations in children diagnosed with a perv...

Tuberculous meningitis is especially common in young children and people with untreated HIV infection, and it kills or disables roughly half of everyone affected. Childhood disease can be prevented by vaccination and by giving prophylactic isoniazid to children exposed to infectious adults, although improvements in worldwide tuberculosis control wo...

Background: Pediatric meningitis remains a common cause of childhood morbidity and mortality in developing countries. Knowledge of the causative organisms in a region is of importance in guiding empiric antibiotic regimes and immunization schedules assisting decisions on primary health-care interventions. Methods: This retrospective review of 55...

Background / Purpose: There are no reports describing the characteristics of myasthenia gravis (MG) in African children as defined by symptom onset before the age of 20 years. One group previously reported the development of an ophthalmoplegic complication in those with AChR-antibody positive generalized MG. This complication occurred almost excl...

To report the characteristics of juvenile-onset (<20 years) myasthenia gravis (MG) in Africa. Six South African centres collected data which included acetylcholine receptor-antibody (AChR-ab) status, delay before diagnosis, MG Foundation of America grade at onset, maximum severity and severity at last visit, therapies, outcomes and complications. W...

Immune suppression predisposes HIV-infected children to opportunistic infections including Mycobacterium tuberculosis. HIV infection increases the risk of progression to active disease and also increases the risk for extrapulmonary involvement, including tuberculous meningitis (TBM). Brain injury in TBM is the consequence of an immune-mediated vasc...

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a potentially life-threatening complication in HIV infected children with tuberculosis (TB) of the central nervous system. HIV-associated TB-IRIS has not been previously described in children with neurotuberculosis. To describe the neurological and neuro-radiological f...

Aims Obstructive sleep apnoea (OSA) has been described in 2 small studies of adults with human immunodeficiency virus (HIV) and appears to be associated with higher body mass index1 and adenotonsillar hypertrophy.2 However, there are few data in children and the possibility of an association with cerebrovascular disease has not been addressed. The...

Although the involvement of immune mechanisms in multiple sclerosis (MS) is undisputed, some argue that there is insufficient evidence to support the hypothesis that MS is an autoimmune disease, and that the difference between immune- and autoimmune disease mechanisms has yet to be clearly delineated. Uncertainties surrounding MS disease pathogenes...