Neurology 2000;54:1103-1109
© 2000 American Academy of Neurology
Articles
Variant Alzheimer’s disease with spastic paraparesis
Clinical characterization
A. Verkkoniemi, MD,
M. Somer, MD, PhD,
J. O. Rinne, MD, PhD,
L. Myllykangas, BM,
R. Crook, BSc,
J. Hardy, PhD,
M. Viitanen, MD, PhD,
H. Kalimo, MD, PhD and
M. Haltia, MD, PhD
From the Departments of Pathology (Drs. Verkkoniemi and Haltia, and L. Myllykangas), University of Helsinki and Helsinki University Central Hospital; the Department of Clinical Neurosciences (Dr. Verkkoniemi), Helsinki University Central Hospital; the Family Federation of Finland (Dr. Somer), Helsinki, Finland; the Turku PET Center (Dr. Rinne) and the Department of Pathology (Dr. Kalimo), Turku University Hospital, Finland; the Karolinska Institutet (Dr. Viitanen), Division of Geriatric Medicine, Huddinge Hospital, Sweden; and the Neurogenetics Laboratory (R. Crook and Dr. Hardy), Mayo Clinic Jacksonville, FL.
Address correspondence and reprint requests to Dr. Auli Verkkoniemi, Department of Clinical Neurosciences, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Helsinki, Finland; e-mail: Aulie{at}DLC.fi
OBJECTIVE: To present the clinical, neuroimaging, and electrophysiologic characteristics of a variant AD phenotype.
BACKGROUND: The authors have identified a large Finnish kindred with presenile dementia and spastic paraparesis due to deletion of exon 9 of presenilin 1. Neuropathologic analysis showed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyloid peptide but lacking congophilic cores.
PATIENTS AND METHODS: Twenty-two affected individuals (16 men and 6 women) were identified in four successive generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine deceased patients were evaluated. Electrophysiologic investigations were available in eight cases. CT or MRI of the head had been performed on 11 patients and PET was performed on three patients. Result:— The mean age at onset (±SD) was 50.9 ± 5.2 years (range 40 to 61 years). Memory impairment was present in all patients. Memory impairment appeared simultaneously with or was preceded by walking difficulty due to spasticity of the lower extremities (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14) in some patients suggested cerebellar involvement. EEG showed intermittent generalized delta-theta activity. Head MRI showed temporal and hippocampal atrophy; PET showed bilateral temporo-parietal hypometabolism.
CONCLUSION: Spastic paraparesis or brisk stretch reflexes of lower extremities or clumsiness of hands combined with dementia suggests this variant of AD.
Key words: Variant AD—Spastic paraparesis—Presenilin 1 mutation.
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129(11):
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[PDF]
|
|
|
|
|
|
|
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|
|
|
|
|
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