Ataxia in children: SAQ

The first child has post-infectious acute cerebellar ataxia. He has an acute onset of a wide-based, staggering gait over one day, one to three weeks after a varicella illness, with a normal conscious state, a purely cerebellar pattern of truncal and gait ataxia with dysmetria and slurred speech, and a normal neurological examination apart from the ataxia. His red-flag screen is entirely negative, with no headache, no vomiting, no papilloedema, no head tilt, no cranial nerve palsy, no altered conscious state, and no focal deficit. This combination is the classic, safe pattern of post-infectious acute cerebellar ataxia, the single most common cause of acute ataxia in a preschool child, and the prognosis is excellent. The second child has Friedreich ataxia, with the cardinal combination of a progressive limb and gait ataxia, absent lower limb reflexes, extensor plantar responses, loss of position and vibration sense, pes cavus, scoliosis, and a hypertrophic cardiomyopathy.

Question 1 (10 marks)

Outline your diagnosis, investigation plan, and management for the four-year-old boy, and explain how you would recognise and act on the red flags that would change that plan. [1]

My diagnosis is post-infectious acute cerebellar ataxia. The four features that make the diagnosis are the acute onset of a wide-based gait over hours to a day, the preceding varicella illness one to three weeks earlier, the preschool age, and the purely cerebellar pattern with a normal conscious state and a normal examination apart from the ataxia. The condition is the single most common cause of acute ataxia in young children, and the diagnosis is clinical. [1]

My investigation plan is to perform no routine tests and no imaging. The diagnosis is clinical, and a child who meets the classic pattern with a normal conscious state and a negative red-flag screen does not need a blood test, a lumbar puncture, or a scan. I would perform a toxicology screen only if I suspected ingestion, which I do not in this child with a clear post-infectious history and no access to medications reported. I would perform a lumbar puncture and imaging only if the red-flag screen or the course changed the picture. [1]

My management is reassurance, observation, and safety-netting advice. I would counsel the family that the condition is self-limiting and that the large majority of children recover fully over weeks to months without specific treatment, as the classic study by Connolly established. I would advise the family to return immediately if the child developed a headache, vomiting, drowsiness, a decline in the conscious state, or a worsening rather than an improving gait, and I would review the child in clinic until the ataxia resolved. [2]

The red flags that would change my plan are the features of a posterior fossa tumour, a cerebellitis, a central nervous system infection, or an ingestion. A headache that is worse in the morning or wakes the child from sleep, effortless early-morning vomiting, papilloedema, a head tilt, a new squint or cranial nerve palsy, a depressed or fluctuating conscious state, a progressive rather than improving course, fever with meningism, or opsoclonus and extreme irritability would each convert the plan from observation to urgent magnetic resonance imaging. The systematic review by Wilne confirmed that headache, nausea and vomiting, and gait abnormality are among the commonest features of a childhood central nervous system tumour, and the cardinal error is discharging a tumour as a post-infectious ataxia. [3]

Question 2 (10 marks)

Discuss the clinical and genetic diagnosis of the thirteen-year-old girl, and outline the principles of her management including the evidence for disease-modifying therapy. [5]

My diagnosis is Friedreich ataxia. The girl has the cardinal constellation of a progressive limb and gait ataxia over eighteen months, absent knee and ankle reflexes, extensor plantar responses, loss of position and vibration sense in the lower limbs, pes cavus, scoliosis, and a hypertrophic cardiomyopathy. The onset is in adolescence, and the combination of absent lower limb reflexes with an extensor plantar response and a sensory ataxia from dorsal column loss is the signature that separates Friedreich ataxia from a pure cerebellar lesion. [5]

My diagnostic test is the targeted genetic test for the GAA trinucleotide repeat expansion in the FXN gene on chromosome nine. Friedreich ataxia is an autosomal recessive disorder, and the GAA repeat expansion reduces frataxin, a mitochondrial protein that assembles iron-sulphur clusters, which is the mechanism that produces the sensory ataxia, the dorsal column loss, and the cardiomyopathy. I would arrange the genetic test as the first and definitive investigation, and I would perform a magnetic resonance imaging to exclude a structural lesion and to document the cerebellar and spinal cord involvement. [5]

The management is multidisciplinary and now includes the first disease-modifying drug. The MOXIe trial showed that omaveloxolone, which activates nuclear factor erythroid 2-related factor 2 and restores mitochondrial function, improved the modified Friedreich Ataxia Rating Scale score compared with placebo, and a delayed-start analysis confirmed a durable benefit, which supports treating early. I would refer her to a Friedreich ataxia or neurology service for consideration of omaveloxolone. [7]

The broader management addresses the multisystem burden. The cardiomyopathy is the leading cause of death, so I would arrange regular cardiology surveillance with echocardiography, screen for diabetes with an annual glucose and glycated haemoglobin, and monitor for scoliosis with orthopaedic input. I would address her mobility with physiotherapy and the timely provision of walking aids and, ultimately, a wheelchair, and I would arrange genetic counselling for the autosomal recessive inheritance, the carrier testing of siblings, and the reproductive options. The prognosis is that of a progressive degenerative disease, with loss of ambulation typically within ten to fifteen years and a reduced life expectancy driven by the cardiomyopathy, but the natural history is heterogeneous and the arrival of omaveloxolone offers the prospect of slowing the decline. [5]