BIOS5130 Week 9 Lecture Part 2 Slides

BIOS5130 WEEK 9 – LECTURE PART 2 CNS Case Study – Infantile Spasms

Introduction

• Presenter: Dr. Emma Hargreaves

• Source: Major & Thiele (2007). Seizures in Children: Laboratory Diagnosis and Management.

Case Overview

• An infant diagnosed at 6 months with epilepsy characterized by:

  • Sudden onset of head-drop seizures.

  • Deteriorating mental development.

Detailed Case Study

Background Information

• Ben's Development:

  • At 4 months: displayed typical developmental milestones, could roll over, hold up head, and reach for objects, reflecting expected neurological growth.

  • By 7 months: exhibited dysregulated motor abilities; notably, he lay listlessly in the crib, suggesting a decline in engagement and mobility, which could indicate underlying neurological disturbances.

  • First seizure incident:

    • Occurred while he was sitting in a high chair, where a sudden head drop was observed, coupled with violent movements indicating a seizure.

Diagnosis

• Diagnosed with Infantile Spasms (West Syndrome):

  • Characterized by head-drop seizures typically occurring between 4 to 7 months of age.

  • Associated with either arrested or deteriorating mental development, which is critical for identifying the need for early intervention.

Treatment Protocol

• Initial Treatment:

  • Administered adrenocorticotropic hormone (ACTH) injections combined with vigabatrin, an anti-epileptic medication, showing a multi-faceted approach to management.

• Mechanism of Action:

  • ACTH increases myelin formation, maintains the integrity of the blood-brain barrier, and enhances GABA binding, which is essential for seizure control.

  • Vigabatrin prolongs GABA's synaptic activity, effectively delaying its breakdown and leading to increased inhibition of neuronal firing, crucial in mitigating seizure activity.

• Outcome:

  • Notably, seizures disappeared before the completion of the one-month treatment course.

  • An improvement in developmental milestones was observed, indicating successful initial intervention.

Infantile Spasms (West Syndrome)

Key Characteristics

• Historical Context: first described in 1841, providing a historical backdrop to this diagnosis.

• Prevalence: Occurs in approximately 1 in 2,500-3,000 children, leading to about 350-400 new cases in the UK annually, highlighting the need for awareness and early detection.

• Typical Onset: Occurs between 3-8 months, with initial symptoms potentially infrequent, leading to misdiagnosis as colic, which can delay appropriate care.

• Seizure Presentation:

  • Characterized by sudden body flexion, typically presenting in clusters lasting seconds, with brief pauses in between, which can be easily overlooked.

Clinical Indicators

• Consequences of Seizures:

  • Can lead to disrupted sleep patterns, irritability, poor feeding, and delayed overall development, necessitating a comprehensive approach to care.

Examination Questions

Question Prompts

• Leaky Blood-Brain Barrier Mechanism:

  • Explains how a compromised blood-brain barrier may induce action potential cascades that ultimately result in seizures, emphasizing the neurophysiological implications of barrier integrity.

• GABA Functionality:

  • Discusses how GABA activation of Cl⁻ channels affects the postsynaptic membrane potential, crucially influencing action potential firing and seizure propensity.

• ACTH Therapy Duration:

  • Discusses the importance of limiting ACTH therapy duration, focusing on potential implications of exogenous versus endogenous hormone actions and effects on the hypothalamic-pituitary-adrenal (HPA) axis.

Follow-Up Case Details

EEG and Imaging

• Six months post-initial treatment:

  • Recurrence of seizures prompted another EEG, which showed abnormal activity without the typical infantile spasms wave patterns, indicating a continued need for evaluation.

  • A request for a PET scan was made to locate seizure activity, with PET scanning viewed as advantageous due