ABSTRACT
The most common form of autosomal recessive hereditary spastic paraplegia is caused by mutations in the SPG11/KIAA1840 gene on chromosome 15q. The nature of the vast majority of SPG11 mutations found to date suggests a loss-of-function mechanism of the encoded protein, spatacsin. The SPG11 phenotype is, in most cases, characterized by a progressive spasticity with neuropathy, cognitive impairment and a thin corpus callosum on brain MRI. Full neuropathological characterization has not been reported to date despite the description of >100 SPG11 mutations. We describe here the clinical and pathological features observed in two unrelated females, members of genetically ascertained SPG11 families originating from Belgium and Italy, respectively. We confirm the presence of lesions of motor tracts in medulla oblongata and spinal cord associated with other lesions of the central nervous system. Interestingly, we report for the first time pathological hallmarks of SPG11 in neurons that include intracytoplasmic granular lysosome-like structures mainly in supratentorial areas, and others in subtentorial areas that are partially reminiscent of those observed in amyotrophic lateral sclerosis, such as ubiquitin and p62 aggregates, except that they are never labelled with anti-TDP-43 or anti-cystatin C. The neuropathological overlap with amyotrophic lateral sclerosis, associated with some shared clinical manifestations, opens up new fields of investigation in the physiopathological continuum of motor neuron degeneration.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Motor Neurons/pathology , Nerve Degeneration/pathology , Spastic Paraplegia, Hereditary/pathology , Adult , Brain/pathology , Female , Ganglia, Spinal/pathology , Humans , Lysosomes/ultrastructure , Male , Medulla Oblongata/pathology , Middle Aged , Mutation , Proteins/genetics , Spastic Paraplegia, Hereditary/diagnosis , Spastic Paraplegia, Hereditary/diagnostic imaging , Spinal Cord/pathologyABSTRACT
Cerebral venous sinus thrombosis is an uncommon condition with a variable clinical presentation, often resulting in a delayed diagnosis. The most common risk factors are pregnancy and puerperium, oral contraceptive use, head injury, dehydration, blood dyscrasias, malignancies, and systemic diseases. We present a nineteen-year-old female in whom a superior sagittal sinus thrombosis was caused by dehydration during diabetic ketoacidosis and led to the diagnosis of new-onset type 1 diabetes mellitus. To our knowledge this is the first published report of a cerebral venous sinus thrombosis in association with diabetic ketoacidosis in an adult.
