CD40 ligand deficiency: neurologic sequelae with radiographic correlation - PubMed (original) (raw)

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CD40 ligand deficiency: neurologic sequelae with radiographic correlation

Shrinivas Bishu et al. Pediatr Neurol. 2009 Dec.

Abstract

Patients with CD40 ligand deficiency are susceptible to central nervous system infections, but to date the neurologic progression or long-term outcome of central nervous system complications have not been reported in detail. Characterizing the central nervous system complications of immune deficiencies can lead to the identification of new pathogens. For this study, clinical data were reviewed on patients with both CD40 ligand deficiency and neurodegeneration, identified from a larger cohort of 31 patients. Five patients had progressive neurologic and cognitive decline in the absence of clinical signs of acute fulminant encephalitis, with anatomic brain abnormalities and high mortality (60%). Despite multiple evaluations, no pathogens were identified in four patients, all of whom were on standard intravenous immunoglobulin therapy at illness presentation. This clinical phenotype of progressive decline without acute fulminant encephalitis is similar to chronic enteroviral encephalitis in X-linked agammaglobulinemia, another condition with severe humoral immune defects. Whether infection secondary to subtherapeutic levels of central nervous system immunoglobulin G (IgG), inadequately protective levels of serum IgG, or impaired CD40 ligand-dependent IgG-independent antiviral responses contributed remains undetermined. Emerging gene-chip techniques applied in patients with primary immune deficiencies may identify heretofore unknown viruses. Prospective neurocognitive and evaluation of patients with CD40 ligand deficiency may identify affected patients before overt clinical signs appear.

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Conflict of interest statement

Conflict of interest: No conflicts reported by any author

Figures

Figure 1

Figure 1. Radiographic findings of patients with CD40 ligand deficiency and neurodegeneration

(A) T1 weighted brain MRI obtained upon presentation in patient 1 and (B) three months later demonstrating progressive cortical atrophy. TR/TE: 400/10 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness. (C) Fluid inversion recovery attenuation weighted MRI obtained in patient 2 at presentation. (D) Patient 2 three years later (one month after completing pleconaril therapy) demonstrating progressive atrophy and periventricular encephalomalacia (arrows). TR/TE: 10,000/145 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness. (E) T1 weighted MRI obtained in patient 4 when 6 years after presenting with neurologic decline and then (F) 4 years later demonstrating progressive atrophy (interval gyral thining/sulcul widening (arrows)). TR/TE: 400/10 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness.

Figure 1

Figure 1. Radiographic findings of patients with CD40 ligand deficiency and neurodegeneration

(A) T1 weighted brain MRI obtained upon presentation in patient 1 and (B) three months later demonstrating progressive cortical atrophy. TR/TE: 400/10 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness. (C) Fluid inversion recovery attenuation weighted MRI obtained in patient 2 at presentation. (D) Patient 2 three years later (one month after completing pleconaril therapy) demonstrating progressive atrophy and periventricular encephalomalacia (arrows). TR/TE: 10,000/145 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness. (E) T1 weighted MRI obtained in patient 4 when 6 years after presenting with neurologic decline and then (F) 4 years later demonstrating progressive atrophy (interval gyral thining/sulcul widening (arrows)). TR/TE: 400/10 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness.

Figure 1

Figure 1. Radiographic findings of patients with CD40 ligand deficiency and neurodegeneration

(A) T1 weighted brain MRI obtained upon presentation in patient 1 and (B) three months later demonstrating progressive cortical atrophy. TR/TE: 400/10 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness. (C) Fluid inversion recovery attenuation weighted MRI obtained in patient 2 at presentation. (D) Patient 2 three years later (one month after completing pleconaril therapy) demonstrating progressive atrophy and periventricular encephalomalacia (arrows). TR/TE: 10,000/145 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness. (E) T1 weighted MRI obtained in patient 4 when 6 years after presenting with neurologic decline and then (F) 4 years later demonstrating progressive atrophy (interval gyral thining/sulcul widening (arrows)). TR/TE: 400/10 ms, field of view: 20–22 cm, matrix: 256 × 192, 1 excitation, 5 mm slice thickness.

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