CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, autosomal recessive, pediatric-onset, rapidly progressive neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 (TPP1) enzyme deficiency, and is characterized by language delay, seizures, rapid cognitive and motor decline, blindness, and early death. No management guidelines exist and there is a paucity of published disease-specific evidence to inform clinical practice, which currently draws upon experience from the field of childhood neurodisability. Twenty-four disease experts were surveyed on CLN2 disease management and a subset met to discuss current practice. Management goals and strategies are consistent among experts globally and are guided by the principles of pediatric palliative care. Goals and interventions evolve as the disease progresses, with a shift in focus from maintenance of function early in the disease to maintenance of quality of life. A multidisciplinary approach is critical for optimal patient care. This work represents an initial step toward the development of consensus-based management guidelines for CLN2 disease.
Advanced imaging techniques, longitudinal follow-up of individuals born extremely preterm into adulthood and improved understanding of risk factors associated with neurologic impairment contribute to recent discoveries. Sensory impairments are often associated with later cognitive and social impairments and therefore represent targets for therapy. All aspects of neurologic development can be affected by preterm delivery. Future research is needed to further elucidate targets for prenatal and postnatal interventions for neuroprotection and to improve outcomes of prematurity.
Background: Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare presentation of a primary central nervous system glial tumor. Methods: Four case reports of PDLG in young males aged 14–24 years are presented. These reports are discussed in the context of the existing literature. Results: The clinical presentation of 4 new cases of PDLG resembled chronic meningitis with and without polyradiculopathy. Spinal fluid studies are typically nondiagnostic, but characteristically show elevated opening pressure, an elevated protein level, and a relative paucity of cellular reaction. An accurate antemortem diagnosis required contrast-enhanced imaging and meningeal biopsy in all 4 of our cases. Treatment strategies including craniospinal radiation and chemotherapeutic approaches, alone or in combination, have not been proven to alter the course of the disease. Initial responses to temozolomide and radiation treatments in all 4 of our cases were promising, resulting in temporary stabilization of the disease and prolonging life expectancy over what was previously reported in the literature. Conclusion: Total neuroaxis contrast-enhanced MRI scanning is required for directing biopsy confirmation and detecting the extent of the disease. More effective therapeutic strategies are needed, but the combination of temozolomide and radiation therapy may slow disease progression.
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