Developmental regression and neurodegeneration — branching viva

Opening branch — the regressing adolescent

A previously well fourteen-year-old presents over ten days with insomnia, agitation, hallucinations, a seizure, and orofacial dyskinesia, with a fluctuating conscious level. The candidate must first recognise this as developmental regression in its subacute form - loss of previously acquired cognitive and behavioural function - and distinguish it from a primary psychiatric disorder. The candidate states that the combination of psychiatric onset, seizures, a movement disorder, and altered consciousness is the phenotype of autoimmune encephalitis, a treatable mimic of neurodegeneration, and that the cardinal error is dismissing the early phase as psychiatric. [3]

The examiner probes the framework. The candidate gives the Graus diagnostic approach, which permits a diagnosis of probable autoimmune encephalitis on the phenotype - subacute onset of psychiatric symptoms, seizures, a movement disorder, autonomic instability, and a decreased level of consciousness - supported by EEG, CSF, or imaging, before the antibody panel confirms it. The teaching point is that the framework exists so that empirical immunotherapy is justified while the panel returns, because the outcome is better the earlier treatment begins. [3] [4]

Second branch — the workup and the genomic question

The examiner asks for the investigation strategy and the immediate management. The candidate gives the tiered approach: a first-line screen with bloods, autoimmune and infective panels, a brain MRI, an EEG, and CSF analysis, with empirical first-line immunotherapy (high-dose corticosteroids plus intravenous immunoglobulin or plasma exchange) started in parallel. The candidate states that a poor early response is the signal to escalate to second-line therapy with rituximab or cyclophosphamide, that an ovarian teratoma must be sought and removed in an adolescent girl, and that most children treated early make a good recovery. The candidate then generalises: for any child with unexplained regression, the workup is developmental history, brain MRI, a sleep EEG, and - when targeted testing is unrevealing - trio exome sequencing as the single highest-yield genetic test. [1] [4]

Third branch — the girl with hand stereotypies

The case shifts to an eighteen-month-old girl who developed normally for the first year but has lost purposeful hand use and begun midline hand-wringing, with a wide-based gait and deceleration of head growth. The candidate diagnoses Rett syndrome, anchored on the period of normal development followed by regression with loss of purposeful hand skills and the emergence of stereotypies, with gait dyspraxia and head-growth deceleration, confirmed by MECP2 molecular testing against the revised 2010 criteria. The candidate distinguishes Rett from autistic regression - which lacks the hand stereotypies, the gait dyspraxia, and the head-growth deceleration - and frames management as supportive, rehabilitative, and surveillance-based across the four-stage course. [2]

Fourth branch — the treatable epileptic encephalopathy

The examiner moves to a six-year-old boy with acquired loss of language comprehension over four months, two brief nocturnal seizures, and a normal waking EEG. The candidate diagnoses Landau-Kleffner syndrome and explains that the epileptiform abnormalities, which may be absent in wakefulness, are markedly activated in sleep - so a sleep EEG is essential and a normal waking trace does not exclude the diagnosis. The wider syndrome of continuous spikes and waves during slow sleep shows electrical status epilepticus of sleep, with global regression and a spike-wave index occupying most of non-rapid-eye-movement sleep. The candidate names the treatment - corticosteroids and antiseizure medication to suppress the electrical status that is driving the cognitive regression - and states that this is a genuinely treatable cause of regression missed when a sleep EEG is not performed. [5]

Closing synthesis

The examiner asks for the single unifying principle. The candidate states that every regressing child reduces to four questions: is this true regression, which pattern group, which tier of the workup names it, and is there a treatable cause whose window is closing. The governing rule is that the treatable causes must be actively excluded before a child is labelled degenerative or palliative, and trio exome is the single highest-yield test when targeted testing is unrevealing. [1] [3]