Table 3.
Ophthalmic and neurologic tests used in paediatric neuroinflammatory/neurodegenerative disorders.
| Test name | Objective | Parameters measured by test | Ranking score | Interpretation of test | OCT features related to ophthalmic or neurological impairment measured by test | ||
|---|---|---|---|---|---|---|---|
| Hamburg CLN3 ophthalmic rating scale | To monitor progression of retinal degeneration in CLN3 disease | VA | BCVA measured in Snellen. | Grade 0 (unaffected) | Score: 14 points. BCVA ≥ 20/25. No retinal degeneration. No EZ or ONL loss. | VA < = 20/160, fundoscopic abnormalities and loss of EZ and ONL by OCT reflect structural and functional retinal damage in patients with CLN3 disease. | Loss of EZ and ONL are present in grade 2 and 3 of Hamburg CLN3 scale. In addition, loss of EZ area is strongly associated with VA loss. |
| Fundoscopy abnormalities | Optic pallor, macular striae, macular orange pigment, peripheral bony spicules, vessel loss. | Grade 1 (affected) | Score between 10–13 points. Subtle retinal degeneration. No EZ or ONL loss. | ||||
| Grade 2 (severely affected) | Score between 5–9 points. Evident retinal degeneration. EZ and ONL loss. | ||||||
| OCT assessment | EZ and ONL integrity. | Grade 3 (end stage) | Score between 0–4 points. BCVA < = 20/160. Optic pallor, macular atrophy with orange pigment deposition, vessel loss and peripheral bone spicules. EZ and ONL loss. | ||||
| modified Disability Rating Scale (mDRS) | To assess severity of disease and monitor treatment effect | Ambulation | Clumsiness, autonomous ataxia gait, outdoor or indoor assisted ambulation, wheelchair-bound. | 1 | Mild disability | The maximum score that a patient can get is 25, representing severe disability in overall neurological impairment. | Thinning of OPL is associated with severe disability in mDRS in patients with Nieman Pick type C disease. |
| Motor response | Tremor, dysmetria/dystonia, seizures. | 2–3 | Partial disability | ||||
| Language | Delayed acquisition, dysarthria, non-verbal communication, absence of communication. | 4–6 | Moderate disability | ||||
| Swallowing | Abnormal chewing, occasional dysphagia, daily dysphagia, nasogastric/gastric button feeding. | 7–11 | Moderately severe | ||||
| Seizures | Occasional seizures, seizures with antiepileptic drugs, seizures resistant to antiepileptic drugs. | 12–16 | Severe | ||||
| Ocular movements | Slow ocular pursuit, vertical ophthalmoplegia, complete ophthalmoplegia. | 17–25 | Extremely severe | ||||
| Assessment and Rating of Ataxia (SARA) | To assess severity of clinical impairment in cerebellar ataxia | Gait | Walking, turning and walking tandem. | 0 | No ataxia | Each domain (gait, stance, sitting, speech, finger chase, nose-finger test, fast alternating hand movements, heel-shin slide) ranked from 0 to 8. SARA score is sum of all domain scores. | The thinning of combined GCL with IPL thickness is associated with worse SARA score in Nieman Pick disease. |
| Stance | Ability to stand in natural position, with feet together in parallel and in tandem. | ||||||
| Sitting | To sit on an examination bed without support of feet, eyes open and arms outstretched to the front. | ||||||
| Speech disturbance | Speech in assessed during normal conversation. | ||||||
| Finger chase | Presence of dysmetria, under/overshooting target (<5 cm, < 15 cm, > 15 cm). | 40 | Most severe ataxia | ||||
| Nose-finger test | Presence of tremor and amplitude of it (< 2 cm, < 5 cm, > 5 cm). | ||||||
| Fast alternating hand movements | Irregularities doing the task. | ||||||
| Heel-shin slide | Abnormalities doing the task. | ||||||
| Expanded Disability Status Scale (EDSS) | To qualify disability and disease progression in patients with MS and other diseases | Ambulation | Ability to walk, requirement of assistance, use of wheelchair or to be restricted to bed. | 0 | Normal neurological status | The lower scale values of test measure impairments based on neurological examination; upper range of scale (> EDSS 6) measures handicaps of patients with MS. Scores from 0 to 3.5 are determined by neurological deficit without impairment of ambulation. | Thinning of peripapillary RNFL is strongly correlated with upper range score in EDSS scale. |
| Pyramidal | Paraparesis, hemiparesis, monoparesis, quadriparesis, monoplegia, paraplegia, hemiplegia, quadriplegia. | 1 | No disability with only minimal signs | ||||
| Cerebellar | Ataxia. | 2 | Minimal disability | ||||
| Brainstem | Nystagmus, extraocular weakness, dysarthria, inability to swallow or speak. | 3 | Moderate disability | ||||
| Sensory | Decrease in touch, pain and position sense. | 4 | Relatively severe disability | ||||
| 5 | Disability affects full daily activities | ||||||
| Bowel and bladder | Urinary hesitancy, urgency or retention. Urinary incontinence. | 6 | Assistance required walking and working | ||||
| 7 | Essentially restricted to walk and work | ||||||
| Visual | VA measured in Snellen. | 8 | Restricted to bed or wheelchair | ||||
| Cerebral | Mood alteration, decrease in mentation, dementia or chronic brain syndrome. | 9 | Bedridden and unable to communicate effectively or eat/swallow | ||||
| 10 | Death | ||||||
CLN3 juvenile ceroid-lipofuscinosis, neuronal 3, VA visual acuity, BCVA best corrected visual acuity, OCT Optical coherence tomography, EZ Ellipsoid zone, ONL outer nuclear layer, OPL outer plexiform layer, cm centimetres, GLC ganglion cell layer, IPL inner plexiform layer, MS multiple sclerosis.