1/84. Reduplicative paramnesia: longitudinal neurobehavioral and neuroimaging analysis. Reduplicative paramnesia (RP) is a delusion in which the patient perceives familiar places, objects, or events to have been duplicated. The current case describes the development of RP in an 81-year-old male following a large right frontal lobe infarction. As the patient had been hospitalized previously with hemorrhagic contusions, neurologic, neuropsychological, and neuroimaging data were obtained both prior to and following RP onset. Psychophysiologic data were obtained following the development of the delusion. Both premorbidly and at follow-up, neuropsychological functioning was characterized by significant impairments of learning and memory and frontal-executive functions. language and visuospatial skills and motor speed were intact both before and after RP onset. The case is described within the context of preexisting theories of RP, and it is surmised that the delusion is secondary to temporal-limbic-frontal dysfunction giving rise to a distorted sense of familiarity and impaired ability to resolve the delusion via reasoning. ( info) |
| Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). This case illustrates that cadasil can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with cadasil closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia. ( info) |
3/84. Treatment of dementia-associated agitation with gabapentin. The authors describe the use of gabapentin in the treatment of 4 outpatients with dementia-associated agitation. On the basis of clinical case reports and the Overt Agitation Severity Scale, all 4 patients had reduced agitation with gabapentin. Three of 4 patients were successfully titrated to a full dose of 2,400mg/day. These findings suggest a possible role for gabapentin in the behavioral management of patients with dementia. ( info) |
| BACKGROUND: The mechanism of a progressive lacunar infarction is not well understood, and changes in ischemic tissue after onset have not yet been clarified clinically. OBJECTIVE: To investigate the pathophysiological characteristics of a case of progressive lacunar infarction using diffusion-weighted and conventional magnetic resonance imaging (MRI) scans. PATIENT: A 73-year-old woman was hospitalized 18 hours after stroke onset and was diagnosed as having a lacunar infarction in the perforating territory of the left middle cerebral artery. Despite treatment, the hemiparesis worsened, with the peak on the fourth day after onset. diffusion-weighted and conventional MRI scans provided clues to the pathogenesis. FINDINGS AND CONCLUSIONS: In the acute stage, gradual enlargement of the hyperintense lesion, reflecting fresh ischemic tissue, and neurological deterioration were observed by serial examination of diffusion-weighted MRI scans. A conventional coronal MRI scan revealed a 2-layered ischemic lesion, suggesting the involvement of perforating arteries. These findings indicated that hemodynamic impairment of the microcirculation in the perforators was the major cause of the lacunar infarction. ( info) |
5/84. De novo mutation in the Notch3 gene causing cadasil. cadasil, an autosomal dominant arteriopathy responsible for stroke and dementia, is caused by strongly stereotyped mutations in the Notch3 gene. We report a patient with a condition strongly suggestive of cadasil (migraine, stroke, and white matter abnormalities), except that this patient did not have any first-degree relatives with similar symptoms. This patient carried a heterozygous Arg182Cys mutation in the Notch3 gene; this mutation was absent in his two biological parents. These data demonstrate the occurrence of a de novo noninherited mutation in the Notch3 gene, which indicates that cadasil should not be rejected in the absence of a family history. Therefore, our finding suggests that cadasil may be more frequent than anticipated. ( info) |
| The authors report on an Italian family with eight affected members who show autosomal dominant migraine with prolonged visual, sensory, motor, and aphasic aura. These symptoms are associated with white matter abnormalities on brain MRI. All living affected members carry a Notch3 mutation (Arg153Cys) previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). White matter abnormalities occur in a variable percentage of the general migraine population; cadasil should be suspected in migraineurs with prolonged atypical aura and white matter abnormalities. ( info) |
| A 63-year-old man was admitted with progressive left hemiparesis and left homonymous hemianopsia of 1 month's duration. During the 2 months before admission, he had suffered from slowly progressive dementia. The diagnosis of right-sided watershed (WS) infarction was made. He exhibited slow progression of dementia and cerebral atrophy during the period of observation after discharge. There was a positive relationship between cerebral atrophy and the degree of dementia. In the present case, WS infarction caused by right internal carotid artery occlusion might be related to dementia and cerebral atrophy. ( info) |
8/84. Cerebral blood flow and glucose metabolism in multi-infarct-dementia related to primary antiphospholipid antibody syndrome. The primary antiphospholipid antibody syndrome (PAPS) has been described in patients with a history of fetal loss, thrombocytopenia and arterial or venous thrombosis. In PAPS, a prothrombotic state is mediated by antiphospholipid antibodies (aPLs) leading to disseminated thromboembolic vascular occlusion. Today, the presence of aPLs in the serum is considered as a distinct risk factor for recurrent stroke in young adults. Some PAPS patients develop a multi-infarct-syndrome with a stepwise decline of higher cortical functions. We report on a 55-year-old man suffering from progressive dementia and PAPS, in whom cerebral glucose metabolism and blood flow were examined by positron emission tomography (PET). Cerebral atrophy and moderate signs of leukaraiosis were detected in magnetic resonance imaging (MRI), whereas the PET scans showed a considerable diffuse impairment of cortical glucose metabolism combined with a reduced cerebral perfusion in the arterial border zones. These findings indicate that PAPS-associated vascular dementia is accompanied by a cortical neuronal loss, presumably caused by a small-vessel disease with immune-mediated intravascular thrombosis. This case shows that pathological findings in PAPS are congruent to cerebral changes of metabolism and blood flow in systemic lupus erythematosus (SLE). ( info) |
9/84. Visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). OBJECTIVES: To evaluate visual electrophysiological responses in subjects with cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). methods: Three subjects (one male and two females, mean age 55.3 /-2.9 years) belonging to an Italian family already diagnosed with cadasil through clinicopathological and genetic studies and 14 control subjects (6 males and 8 females, mean age 52.7 /-3.6 years) were enrolled in the study. Flash electroretinogram (ERG), oscillatory potentials (OPs) and simultaneous recordings of pattern electroretinogram (PERG) and visual evoked potentials (VEPs) were assessed in all 3 subjects with cadasil and age-matched controls. RESULTS: Subjects with cadasil showed: reduced ERG, OP and PERG (N35-P50, P50-N95) amplitudes with respect to our normal limits; delayed PERG (N35, P50) and VEP (P100) implicit times when compared with our normal limits; and VEP (N75-P100) amplitudes and retinocortical times within our normal limits. CONCLUSIONS: Subjects with cadasil present a dysfunction in the outer, middle and innermost retinal layers when the index of neural conduction in the postretinal visual pathways is normal. The delay in visual cortical responses observed in subjects with cadasil may be ascribable to retinal impairment with a possible functional sparing of the postretinal visual structures. ( info) |
10/84. Arg133Cys mutation of Notch3 in two unrelated Japanese families with cadasil. OBJECTIVE: More than 80 unrelated, but all Caucasian, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil), originating from various communities around the world, have been molecularly identified. To clarify the occurrence of cadasil in Orientals, we investigated Japanese families presenting as cadasil. methods: We performed the PCR-SSCP and sequence analyses using genomic dna, isolated from venous blood of participants under informed consent. PATIENTS: We identified two unrelated Japanese families with cadasil, including 5 affected members through 2 generations. RESULTS: Each of the affected individuals developed recurrent strokes without risk factors resulting in progressive dementia, pseudobulbar palsy, and gait disturbances which started after the fifth decade of life. Although affected individuals had no vascular risk factors, they showed various degrees of narrowing of retinal arteries. Their MRI/CTs showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECT imaging, there was severe hypoperfusion in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials (GOM) within the basal lamina of pericytes in muscular capillaries. On PCR-SSCP and sequence analyses, a heterozygous Arg133Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for cadasil mutations in Caucasian families. None of the non-affected members nor the 50 Japanese normal controls revealed this mutation. CONCLUSION: Thus, our results confirm that cadasil is a geographically widespread disorder caused by a Notch3 mutation. ( info) |