PAE508 — Diseases of Central Nervous System, Muscles and Bones: Lecture Note

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la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS

la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS Course code: PAE 508 Course title: Diseases of Central Nervous System, Muscles and Bones Course credit load: 2 Units Series 1: Evaluation and Management of CNS Infections • Part 1.1: Aetiology and Pathophysiology of CNS Infections o Sub Part 1.1.1: Common aetiologic agents of CNS infections o Sub Part 1.1.2: Viral and other causes of CNS infection o Sub Part 1.1.3: Pathophysiology of CNS infections • Part 1.2: Clinical Features and Evaluation of Suspected CNS Infection o Sub Part 1.2.1: Clinical features and signs of meningeal irritation o Sub Part 1.2.2: Differential diagnosis of CNS infection o Sub Part 1.2.3: Evaluation of suspected CNS infection and lumbar puncture • Part 1.3: Acute Bacterial Meningitis o Sub Part 1.3.1: Clinical features of acute bacterial meningitis o Sub Part 1.3.2: Diagnosis of acute bacterial meningitis o Sub Part 1.3.3: Management of acute bacterial meningitis • Part 1.4: Tuberculous Meningitis and Complications of CNS Infections o Sub Part 1.4.1: Clinical features of tuberculous meningitis o Sub Part 1.4.2: Diagnosis and management of tuberculous meningitis o Sub Part 1.4.3: Complications and prognosis of CNS infections Introduction Picture a two year old brought to the emergency unit with high fever, irritability, and a stiff neck, deteriorating rapidly over a few hours, a presentation that demands urgent recognition and treatment given the genuine risk of severe, lasting harm from a central nervous system infection if diagnosis and treatment are delayed. This Series opens the PAE 508 course by building a thorough understanding of the aetiology, pathophysiology, evaluation, and management of CNS

la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS infections in children, a foundation for the wider range of central nervous system, muscle, and bone conditions addressed throughout this course. The aim of this Series is to equip you with the knowledge required to understand the causes and pathophysiology of CNS infections, evaluate a child with suspected CNS infection, and recognise and manage acute bacterial meningitis and tuberculous meningitis. This Series begins with the aetiology and pathophysiology of CNS infections, before turning to their clinical features and evaluation. Next, we examine acute bacterial meningitis, before concluding with tuberculous meningitis and the complications of CNS infections. Series Learning Outcomes At the end of this Series, you should be able to: • SLO 1.1: describe the common aetiologies of CNS infections, including bacterial, viral, and other causes, • SLO 1.2: describe the pathophysiology of CNS infections, • SLO 1.3: list the symptoms and signs attributed to CNS infections, including signs of meningeal irritation, • SLO 1.4: list the differential diagnosis of CNS infections, • SLO 1.5: describe the evaluation of a patient with suspected CNS infection, including the indications and contraindications for lumbar puncture, • SLO 1.6: describe the clinical features, diagnosis, and management of acute bacterial meningitis, • SLO 1.7: describe the clinical features, diagnosis, and management of tuberculous meningitis, and • SLO 1.8: enumerate the complications and prognosis of CNS infections. 1.1 Aetiology and Pathophysiology of CNS Infections 1.1.1 common aetiologic agents of CNS infections Bacterial, viral, and other organisms each cause a distinct picture Central nervous system infections in children can be caused by a wide range of organisms, broadly classified into bacterial, viral, and other causes, including fungal and parasitic organisms, with the specific likely causative agent varying considerably according to the child's

la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS age, immunisation status, and immune competence, meaning these factors should always be actively considered when evaluating a child with a suspected CNS infection. Common bacterial causes of meningitis in children include *Streptococcus pneumoniae*, *Neisseria meningitidis*, and, particularly in young infants, Group B Streptococcus and *Escherichia coli*, while *Haemophilus influenzae type b*, once a leading cause, has become considerably less common in settings with good vaccination coverage, discussed in an earlier course, illustrating the direct impact of immunisation programmes on the epidemiology of this serious infection. Fill in the blank: Common bacterial causes of meningitis include Streptococcus pneumoniae and Neisseria ________. 1.1.2 viral and other causes of CNS infection Viral causes of CNS infection include enteroviruses, among the most common causes of viral meningitis in children, herpes simplex virus, particularly important given its potential for severe encephalitis with significant morbidity if not promptly treated, and, in specific epidemiological contexts, other viruses such as measles virus, which can cause a delayed, serious complication discussed in an earlier course, and various arboviruses. Tuberculous meningitis, caused by *Mycobacterium tuberculosis*, discussed in detail in an earlier course and again later in this Series, represents an important cause of CNS infection in high tuberculosis burden settings, including Nigeria, and, less commonly, fungal organisms can cause CNS infection, particularly in immunocompromised children, meaning the breadth of possible causative organisms genuinely requires a structured, systematic diagnostic approach rather than assuming a single likely cause. Fill in the blank: Herpes simplex virus is particularly important given its potential for severe ________ with significant morbidity. 1.1.3 pathophysiology of CNS infections CNS infection typically begins with organisms gaining access to the central nervous system through haematogenous spread, following bacteraemia or viraemia, or, less commonly, through direct extension from a nearby infected structure, such as sinusitis or otitis media, or, rarely, following direct inoculation, such as after neurosurgery or penetrating head trauma. Once within the subarachnoid space, the resulting inflammatory response, while intended to help clear the infection, itself contributes significantly to the pathophysiology of CNS infection, causing cerebral oedema, raised intracranial pressure, and, in severe cases, vasculitis

la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS affecting the cerebral blood vessels, meaning much of the clinical picture and potential complications of CNS infection reflect this host inflammatory response rather than direct effects of the organism alone. Fill in the blank: Once within the subarachnoid space, the resulting inflammatory response contributes significantly to cerebral oedema and raised intracranial ________. Figure 1.1: The meninges and subarachnoid space surrounding the brain. Pilot questions 1.1 1. List three common bacterial causes of meningitis in children. (Linked to SLO 1.1) 2. Explain why Haemophilus influenzae type b has become a less common cause of meningitis. (Linked to SLO 1.1) 3. List two common viral causes of CNS infection in children. (Linked to SLO 1.1) 4. Describe the routes by which organisms gain access to the central nervous system. (Linked to SLO 1.2) 5. Explain how the host inflammatory response contributes to the pathophysiology of CNS infection. (Linked to SLO 1.2)

la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS 1.2 Clinical Features and Evaluation of Suspected CNS Infection 1.2.1 clinical features and signs of meningeal irritation Presentation varies considerably with age Clinical features of CNS infection include fever, headache, vomiting, altered consciousness, and irritability, though presentation in young infants is frequently non-specific, including poor feeding, lethargy, and temperature instability, without the more classic features seen in older children, meaning a high index of suspicion is essential when evaluating an unwell young infant even without obvious localising features. Signs of meningeal irritation include neck stiffness, Kernig's sign, pain and resistance on extending the knee with the hip flexed, and Brudzinski's sign, involuntary flexion of the hips and knees when the neck is passively flexed, though these specific signs are frequently absent or unreliable in young infants, in whom a bulging anterior fontanelle may instead provide an important clue to raised intracranial pressure from underlying meningitis. Fill in the blank: A bulging anterior fontanelle in a young infant may provide an important clue to raised ________ pressure from underlying meningitis. 1.2.2 differential diagnosis of CNS infection The differential diagnosis of a child with features suggestive of CNS infection includes other causes of fever with altered consciousness or neurological symptoms, such as febrile seizure, discussed in a later Series of this course, cerebral malaria in endemic areas, discussed in an earlier course, and, less commonly, non-infective causes of meningeal irritation or raised intracranial pressure, such as subarachnoid haemorrhage. Careful clinical assessment, together with appropriate investigation discussed in the next sub-Part, is generally required to distinguish between these possibilities, since several of these conditions can present with genuinely overlapping clinical features, and a systematic, structured approach to evaluation, rather than relying on a single clinical feature in isolation, is essential to reach an accurate diagnosis promptly. Fill in the blank: Cerebral malaria is an important differential diagnosis for CNS infection in ________ areas.

la-NET | ONLINE LEARNING VIDEO PLATFORM FOR POST-SECONDARY & HIGHER INSTITUTION STUDENTS 1.2.3 evaluation of suspected CNS infection and lumbar puncture Evaluation of a child with suspected CNS infection includes a detailed history and examination, together with laboratory investigations, including full blood count, blood culture, and, centrally, lumbar puncture for cerebrospinal fluid analysis, which remains the key investigation for confirming or excluding CNS infection and identifying the likely causative organism, discussed further later in this Series. Indications for lumbar puncture include clinical

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