Worster-Drought et al. (1933) described 9 affected persons in 3 generations. Onset occurred between 40 and 60 years of age with early onset of spasticity with increased deep tendon reflexes and tone. Muscular rigidity was present only late ... Worster-Drought et al. (1933) described 9 affected persons in 3 generations. Onset occurred between 40 and 60 years of age with early onset of spasticity with increased deep tendon reflexes and tone. Muscular rigidity was present only late in the illness, with legs maintained rigidly in extension with pronounced resistance to passive movement in any direction. There was truncal ataxia and Romberg sign, but no impairment of the optic nerves. No tremors, spontaneous movements, or sensory changes were observed. Mental deterioration was progressive, with survival as long as 13 years after onset. It began with apathy and impaired memory for recent events, and progressed to complete disorientation, with monosyllabic speech and paucity of spontaneous movement. Paresis of pyramidal and extrapyramidal type is rare in Pick disease and occurs late. No male-to-male transmission was noted by Worster-Drought et al. (1940), although 12 persons in 3 generations were affected. Pathologic examination of 1 patient by Worster-Drought et al. (1940) demonstrated widespread demyelination of the brain, especially around small hyalinized blood vessels which were surrounded by distinctive densely woven tangles of fibers and microglia that were easily distinguishable from the senile plaques seen in Alzheimer disease (AD; 104300). The perivascular formations distinguished the disorder from Binswanger disease. There was little neuronal loss, except of some cerebellar Purkinje cells, and hippocampal neurofibrillary tangles were considerably less abundant than in Alzheimer disease. The corpus callosum was severely affected, but there was sparing of U-fibers. Hyalinization of small vessels in the white matter and pia distinguished the disorder from Creutzfeldt-Jakob disease (123400), in which the blood vessels are normal. There was no abnormality of the adrenal glands. There was mild elevation of CSF protein but no serologic evidence of syphilis. Plant et al. (1990) noted that the affected sibs described by Griffiths et al. (1982) shared a common ancestor with the family described by Worster-Drought et al. (1940). They provided clinical and pathologic information on an additional family member. An MRI scan taken 3 years after the onset of symptoms at age 58 demonstrated extensive alteration of signal intensity in periventricular white matter, with sparing of U fibers, as well as abnormal signal intensity in brainstem and cerebellar white matter. Postmortem examination demonstrated small cystic infarctions in the deep periventricular white matter as well as more diffuse abnormality of the white matter, particularly in the parietal and occipital lobes. Histologic findings were similar to those reported by Worster-Drought et al. (1940), with congophilia and faint PAS-positivity noted in perivascular plaques.
Studying amyloid fibrils from a patient described by Plant et al. (1990), Vidal et al. (1999) identified a unique 4-kD protein subunit, which they called ABRI. This highly insoluble peptide is a fragment of a putative type II ... Studying amyloid fibrils from a patient described by Plant et al. (1990), Vidal et al. (1999) identified a unique 4-kD protein subunit, which they called ABRI. This highly insoluble peptide is a fragment of a putative type II single-spanning transmembrane precursor that is encoded by the BRI gene, located on chromosome 13. A single base substitution at the stop codon of ITM2B generates a longer open reading frame, resulting in a larger, 277-residue precursor (603904.0001). Release of the 34 C-terminal amino acids from the mutated precursor generates the ABRI subunit. Antibodies against the amyloid or homologous synthetic peptides recognize both parenchymal and vascular lesions in FBD patients. The point mutation at the stop codon of ITM2B results in the generation of the ABRI peptide, which is deposited as amyloid fibrils causing neuronal dysfunction and dementia.