Developmental regression and neurodegeneration — formative SAQs

Question 1 (10 marks)

A previously well fourteen-year-old girl is brought to the emergency department after ten days of insomnia, agitation, and visual hallucinations, followed by a generalised tonic-clonic seizure. On examination she is intermittently distractible, has repetitive orofacial chewing movements, and her conscious level fluctuates. Basic bloods, a first brain MRI, and a routine waking EEG are unrevealing. ^{[3] [4]}

(a) Define developmental regression and explain why this presentation is a neurological emergency rather than a primary psychiatric disorder. (3 marks) ^[3]

(b) Give the most likely diagnosis and outline the clinical framework that justifies acting before the antibody result returns. (4 marks) ^{[3] [4]}

(c) Describe the immediate management, including the first-line treatment and the investigations sent in parallel. (3 marks) ^[4]

Model answer

Developmental regression is the loss of previously acquired milestones, distinguished from delay, plateau, and a static deficit by a trajectory that was demonstrably higher six months ago than today. This presentation is a neurological emergency because the combination of subacute psychiatric onset, seizures, a movement disorder, and a fluctuating conscious level is the phenotype of autoimmune encephalitis, a disorder that is fully reversible with early immunotherapy and worsens - sometimes irreversibly - with delay. Dismissing it as a primary psychiatric disorder in its early phase is the cardinal error, because the window for recovery is measured in days to weeks. ^[3]

The most likely diagnosis is anti-NMDA-receptor antibody encephalitis. The Graus diagnostic framework permits a diagnosis of probable autoimmune encephalitis on the clinical phenotype - subacute onset of at least three of psychiatric symptoms, seizures, a movement disorder, autonomic instability, and a decreased level of consciousness - supported by an abnormal EEG, CSF, or brain MRI, before the cell-based antibody panel confirms it. The framework exists precisely so that empirical immunotherapy is justified before the result returns, because the panel can take weeks and the outcome is better the earlier treatment begins. ^{[3] [4]}

The immediate management is urgent paediatric neurology and neuroimmunology referral with first-line immunotherapy - high-dose methylprednisolone combined with intravenous immunoglobulin or plasma exchange - while sending CSF and serum for the autoimmune encephalitis panel, screening for an ovarian teratoma in an adolescent girl, and providing supportive care for seizures, dysautonomia, and airway protection. A poor early response is the signal to escalate to second-line therapy with rituximab or cyclophosphamide. ^[4]