Article Figures & Data
Figures
- Fig 1.
MR imaging findings in end-stage INCL. T1-weighted (A) and T2-weighted (B) images in the plane defined by the anterior and posterior commissures. These images demonstrate findings that include extreme atrophy, near-complete lack of gray matter, extensive abnormal signal in the white matter, loss of internal landmarks separating the basal ganglia, and subdural effusions.
- Fig 2.
Thalamus volume measurements in patients with INCL. Due to lack of visible boundaries of the thalamus (secondary to disease-related alterations in intrinsic contrast), an ellipsoidal approximation to the volume was made on the basis of brain surface landmarks. Thalamus volumes were out of the normal range by the time of our earliest measurements and further decreased with time. The equation for the best curve fit is shown. We did not detect a difference between INCL in boys and girls (P = .98). The normal curve reflects thalamus volumes measured on 23 healthy volunteers 1.1–9.6 years of age participating in other studies at our institution; for the healthy volunteers, we did not find a statistical difference between boys and girls (P = .89) or between right and left (P = .86) (dark line = mean, light lines = ±2 SDs). For comparison, the onset ages of major clinical findings (mean and 95% CI) observed in our patients are plotted below the volume curve. A indicates developmental regression; B, cerebral atrophy noted in clinical MR imaging report; C, myoclonic jerks and seizures; D, loss of vision; E, deceleration of head growth; F, isoelectric visual-evoked potentials; and G, isoelectric EEG or electroretinogram.
- Fig 3.
Brain stem volume measurements in patients with INCL. Brain stem volumes decreased with time, dropping below the 2.5th percentile before 3 years of age. The equation for the best curve fit is shown. We did not detect a difference between INCL in boys and girls (P = .88). We defined the brain stem as including the cerebral peduncles, midbrain, pons, and medulla. The normal curve reflects brain stem volumes measured on 23 healthy volunteers 1.1–9.6 years of age participating in other studies at our institution; for the healthy volunteers, we did not find a statistical difference between boys and girls (P = .94) (dark line = mean, light lines = ±2 SDs). For comparison, the onset ages of major symptoms (mean and 95% CI) observed in our patients are plotted below the volume curve. A indicates developmental regression; B, cerebral atrophy noted in clinical MR imaging report; C, myoclonic jerks and seizures; D, loss of vision; E, deceleration of head growth; F, isoelectric visual-evoked potentials; and G, isoelectric EEG or electroretinogram.
- Fig 4.
Cerebellum volume measurements in patients with INCL. Cerebellar volumes were initially near normal but decreased with time and dropped below the 2.5th percentile by about 2.5 years of age. The equation for the best curve fit is shown. We did not detect a difference between INCL in boys and girls (P = .94). We included the cerebellar peduncles in our measurement of cerebellar volume. The normal curve reflects cerebellum volumes measured on 23 healthy volunteers 1.1–9.6 years of age participating in other studies at our institution; for the healthy volunteers, we did not find a statistical difference between boys and girls (P = .91) (dark line = mean, light lines = ±2 SDs). For comparison, the onset ages of major symptoms (mean and 95% CI) observed in our patients are plotted below the volume curve. A indicates developmental regression; B, cerebral atrophy noted in clinical MR imaging report; C, myoclonic jerks and seizures; D, loss of vision; E, deceleration of head growth; F, isoelectric visual-evoked potentials; and G, isoelectric EEG or electroretinogram.
- Fig 5.
Cerebrum volume measurements in patients with INCL. Even our earliest measurements of cerebral volumes were lower than normal, and volumes decreased dramatically with time. The equation for the best curve fit is shown. We did not detect a difference between INCL in boys and girls (P = .94). We defined the cerebrum as including the deep nuclei but not the cerebral peduncles. The normal curve reflects cerebrum volumes measured on 23 healthy volunteers 1.1–9.6 years of age participating in other studies at our institution; for the healthy volunteers, we did not find a statistical difference between boys and girls (P = .78) (dark line = mean, light lines = ±2 SDs). For comparison, the onset ages of major symptoms (mean and 95% CI) observed in our patients are plotted below the volume curve. A indicates developmental regression; B, cerebral atrophy noted in clinical MR imaging report; C, myoclonic jerks and seizures; D, loss of vision; E, deceleration of head growth; F, isoelectric visual-evoked potentials; and G, isoelectric EEG or electroretinogram.
- Fig 6.
Total brain volume measurements in patients with INCL. Total brain volumes (dominated by the cerebral volume) were initially lower than normal and decreased dramatically with time. The equation for the best curve fit is shown. We did not detect a difference between INCL in boys and girls (P = .96). The normal curve reflects total brain volumes measured on 23 healthy volunteers 1.1–9.6 years of age participating in other studies at our institution; for the healthy volunteers, we did not find a statistical difference between boys and girls (P = .80) (dark line = mean, light lines = ±2SD). For comparison, the onset ages of major symptoms (mean and 95% CI) observed in our patients are plotted below the volume curve. A indicates developmental regression; B, cerebral atrophy noted in clinical MR imaging report; C, myoclonic jerks and seizures; D, loss of vision; E, deceleration of head growth; F, isoelectric visual-evoked potentials; and G, isoelectric EEG or electroretinogram.
- Fig 7.
Relative segmental volumes in patients with INCL. A, In INCL, the cerebellum is large relative to the cerebrum, reflecting the observation that volume loss begins earlier and progresses faster in the cerebrum than elsewhere in the brain. The ratio initially rises as cerebral loss outpaces cerebellar loss and decreases later because the cerebrum reaches asymptotic volume earlier than the cerebellum. B, In INCL, the thalamus becomes somewhat large relative to the cerebrum for a while, reflecting the tight linkage between the volumes of these structures with a bit of a delay in involvement of the thalamus relative to the cerebrum. C, In INCL, the brain stem is also large relative to the cerebrum, with a later peak relative to both the thalamus/cerebrum ratio and cerebellum/cerebrum ratio, indicating that the brain stem is involved last among the structures that we measured. In all plots, the equation describes the best curve fit to the INCL results. We did not detect a difference between boys and girls for either patients with INCL or healthy volunteers. The normal curves reflect volume ratios measured on 23 healthy volunteers 1.1–9.6 years of age participating in other studies at our institution (dark line = mean, light lines = ±2 SDs).
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