Acalculia in Autopsy-Proven Corticobasal Degeneration
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Acalculia in Autopsy-Proven Corticobasal Degeneration Figure Imaging and pathologic features of corticobasal degeneration (A) Gross atrophy in parietal lobe (asterisk) of case 1. (B) Hematoxylin-eosin (H-E) preparation of the angular gyrus of case 1 at 10ϫ magnification showing significant neuronal dropout and gliosis in the superficial cortical layers. (C) PHF stain for tau in the cortex of the angular gyrus of case 1 at 60ϫ magnifica- tion showing balloon cells (arrow). (D) PHF stain for tau in the white matter of the angular gyrus of case 1 at 60ϫ magnification showing an astrocytic plaque (arrowhead). (E) T1 magnetization-prepared rapid gradient echo MRI sequence showing bilateral parietal-occipital atrophy in coronal (y ϭϪ60), sagittal (left hemisphere) (x ϭϪ47), and axial (z ϭϩ14) views of case 2. orticobasal degeneration (CBD) is a neurodegenerative condition presenting with an asymmetric extrapyramidal disorder, cortical sensory loss, and apraxia. While the original case descriptions men- Ctioned acalculia,1 few studies have investigated this,2,3 and reports of acalculia in autopsy-proven CBD are very rare. We detail 2 autopsy-defined CBD cases with acalculia to emphasize that CBD compromises cognitive functioning due to disease that includes parietal cortex. CASE REPORTS Case 1. A 72-year-old right-handed woman with hypertension and hypothyroidism was evaluated for progressive cognitive and motor difficulties over 3 years. She first noted writing difficulty. Her right hand began performing involuntary, semi-purposeful movements. She required increasing assistance dressing and cutting food. She misjudged spatial relationships while driving and cooking. She had several falls. Examination revealed Mini-Mental State Examination (MMSE) score of 27. She had ideomotor apraxia, slowed writing, and difficulty copying geometric designs. Number knowledge was impaired, including mis- counting “X” marks on a paper and erring during oral and written calculations (e.g., given “9 ϩ 12,” she responded “20”). Memory, digit span, reading, comprehension, and speech were intact. She had axial rigidity and decreased right arm swing, but no other involuntary movements. Neuropsychological evaluation (z scores relative to 25 demographically matched controls) revealed deficits on spatial tasks (e.g., geometric figure copy z ϭϪ7.74), mild executive dysfunction (e.g., animal category naming fluency z ϭϪ1.90), and preserved language (e.g., Boston Naming test z ϭϪ0.86) and memory (delayed recall of a 10-word list z ϭ 0.02). MRI Copyright © 2011 by AAN Enterprises, Inc. S61 showed parietal atrophy. Over the next 18 features, including dystonia, rigidity, gait impair- months, ideomotor apraxia worsened, and she de- ment, and alien limb phenomena.4,5 Cognitive defi- veloped apractic agraphia and spatial alexia. Num- cits are common, including apraxia, spatial ber knowledge declined, including miscounting difficulties, executive limitations, effortful speech, small arrays of objects and erring with single-digit distorted handwriting, and altered personality. Cor- calculations (2 ϩ 3 ϭ 7; 3 ϩ 4 ϭ 6). She devel- tical sensory loss is typical, but memory difficulty is oped an “alien hand” on the right, complaining “it’ll modest.6 While CBD often initially presents in a lat- fight you,” cortical sensory loss, and increasing axial ri- eralized manner, contralateral features invariably gidity. The patient died 5 years after symptom onset. emerge longitudinally. CBD, a frequent neuropatho- Autopsy revealed gross symmetric parietal atrophy (fig- logic correlate of CBS, affects frontal and parietal corti- ure, A). Microscopic examination showed severe neuro- cal and white matter regions and the basal ganglia most nal dropout and gliosis in the superficial cortical layers profoundly, but temporal and hippocampal regions (figure, B), with tau-positive neuronal (figure, C) tend to be less compromised.6 and glial (figure, D) inclusions bilaterally in the In 15 patients with autopsy-proven CBD that in- parietal lobe and throughout the cerebrum, basal cluded the 2 cases detailed here, acalculia was noted in ganglia, thalamus, and midbrain, consistent with 28.6%, although this was thought to be an underesti- the pathologic diagnosis of CBD. mation since calculations were not often examined.6 Acalculia is caused by disease in either hemisphere. Pa- Case 2. A 60-year-old right-handed man with a his- tients with CBS have significant impairments estimat- tory of treated B12 deficiency presented with wors- ing and comparing quantities, performing calculations ening drawing and writing over 2 years that with small numerosities, and using quantity knowledge interfered with work. He could not locate the sink in to support word meaning.2,3,7 These deficits, evident for his home or park his car. Cutlery was difficult to use, both Arabic numerals and nonverbal dot arrays, under- and he noticed difficulty with calculations and word- line their degraded mental representation of quantity finding. Examination revealed MMSE score of 22. and number knowledge. MRI in CBS regularly shows He had spatial deficits copying a geometric design. parietal atrophy, including areas associated with num- There was ideomotor apraxia, apractic agraphia, left- ber knowledge.3 right discrimination difficulty, finger agnosia, and Cognitive difficulties are common in extrapyra- mild anomia. Simple oral calculations were impaired, midal disorders. They are often related to disruption including single-digit oral and written addition er- of a frontal-striatal loop that compromises executive rors (50% correct) and poor object counting. Mem- resources. These CBD cases emphasize that cognitive ory was intact. Tone was more rigid in right than left abnormalities in extrapyramidal disorders may also limbs, with axial rigidity but no other involuntary involve degeneration of parietal regions. movements. There was a cortical sensory deficit. Neuropsychological evaluation revealed impaired Alexander Pantelyat, MD, Michael Dreyfuss, BA, spatial (e.g., geometric figure copy z ϭϪ5.89) and Peachie Moore, BA, Rachel Gross, MD, executive (animal category naming fluency z ϭ Theresa Schuck, BSc, David Irwin, MD, Ϫ2.66) functioning, with intact memory (delayed John Trojanowski, MD, PhD, Murray Grossman, MD recognition of a 10-word list z ϭϪ1.01) and lan- guage (Boston Naming test z ϭϪ0.86). MRI dem- From the Departments of Neurology (A.P., M.D., P.M., R.G., M.G.) and Pathology and Laboratory Medicine (T.S., D.I., J.T.), onstrated symmetric bilateral parietal occipital University of Pennsylvania School of Medicine, Philadelphia. atrophy (figure, E). Over the next year, there was Study funding: Supported in part by the NIH (NS44266, worsening apraxia, writing, naming, and walking. At AG17586, AG15116, NS53488, AG32953). autopsy 3 years following presentation, histopatho- Disclosure: Dr. Pantelyat, M. Dreyfuss, and Dr. Moore report no logic examination revealed neuronal loss and gliosis disclosures. Dr. Gross has received research fellow/trainee support as well as tau-positive changes consistent with CBD. from the American Academy of Neurology Foundation. T. Schuck receives research support from the NIH (NIA, NINDS) and from Marian S. Ware Drug Discovery. Dr. Irwin has received research DISCUSSION CBS, the clinical diagnosis of these 2 fellow/trainee support from the NIH/NIA. Dr. Trojanowski has re- cases, is a disorder characterized by lateralized motor ceived funding for travel and honoraria from Takeda Pharmaceuti- cal Company Ltd.; has received speaker honoraria from Pfizer Inc.; serves as an Associate Editor of Alzheimer’s & Dementia; may ac- Acalculia in Autopsy-Proven Corticobasal Degeneration crue revenue on patents re: Modified avidin-biotin technique, Method of stabilizing microtubules to treat Alzheimer’s disease, • Cognitive difficulties are common in extrapyramidal disorders. Method of detecting abnormally phosphorylated tau, Method of • Reports of acalculia in autopsy-proven CBD are rare. screening for Alzheimer’s disease or disease associated with the accu- • CBD compromises cognitive functioning due to disease that includes mulation of paired helical filaments, Compositions and methods parietal cortex. for producing and using homogeneous neuronal cell transplants, Rat comprising straight filaments in its brain, Compositions and S62 Neurology: Clinical Practice 76 (Suppl 2) February 15, 2011 methods for producing and using homogeneous neuronal cell REFERENCES transplants to treat neurodegenerative disorders and brain and 1. Rebeiz JJ, Kolodny EH, Richardson EP. Corticodenta- spinal cord injuries, Diagnostic methods for Alzheimer’s disease tonigral degeneration with neuronal achromasia. Arch by detection of multiple MRNAs, Methods and compositions for Neurol 1968;18:20–33. determining lipid peroxidation levels in oxidant stress syndromes 2. 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