Accepted Manuscript Acute stroke presenting with isolated acalculia Michael Grimaldi, Rebecca Jeanmonod PII: DOI: Reference: S0735-6757(18)30503-5 doi:10.1016/j.ajem.2018.06.038 YAJEM 57618 To appear in: American Journal of Emergency Medicine Received date: Accepted date: 13 June 2018 15 June 2018 Please cite this article as: Michael Grimaldi, Rebecca Jeanmonod , Acute stroke presenting with isolated acalculia. Yajem (2018), doi:10.1016/j.ajem.2018.06.038 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Title: Acute Stroke Presenting with Isolated Acalculia Authors: Michael Grimaldi, MD Rebecca Jeanmonod, MD (corresponding author): T rebeccajeanmonod@yahoo.com IP St. Luke’s University Health Network (for all authors) CR 801 Ostrum Street Bethlehem, PA 18015 US USA 610-838-6147 AN No fax number M Word count 1750 Author contributions: Study conception: MG, RJ PT Study design: MG, RJ ED Presentations: None CE Drafting of manuscript: MG, RJ Editing and revision of manuscript: MG, RJ AC Responsible for manuscript as a whole: MG, RJ Conflict of interest statement: All authors have no conflicts of interest to disclose. Running title: Stroke with Isolated Acalculia Key words: stroke, acalculia ACCEPTED MANUSCRIPT Abstract IP T Acalculia is defined as the inability to mentally manipulate numbers for simple calculations. It may occur in dementia, central nervous system (CNS) neoplasm, and stroke1. Lesions of the left parietal cortex are the principal cause. When acalculia occurs in stroke, it is generally associated with other deficits in speech, sensation, or motor function. We report the case of a 63-year-old male with a 1 day history of isolated acalculia that was found to have a left parietal lobe infarct with several smaller infarcts in the left occipital lobe. The diagnosis of stroke should be considered in all patients experiencing acute difficulty with mathematics, reading, or writing, even in the absence of other deficits. CR The Case CE PT ED M AN US A 63-year-old African American male presented to the Emergency Department (ED) with a 1 day history of “confusion.” On further questioning, the patient reported that since approximately 2300 on the night prior to his presentation, he had been experiencing difficulty distinguishing between and working with numbers. He was unable to unlock his smartphone because he could not differentiate between the numbers to enter his passcode. Earlier on the day of presentation, the patient and his wife reported that the patient had significant difficulty filling out paperwork at the bank because he could not comprehend or manipulate the numbers involved. The patient had never experienced similar symptoms. Otherwise, the patient felt well. He had had no recent illnesses, changes in medications, or hospitalizations. He denied headache, vision changes, numbness and weakness of the extremities, aphasia, or ataxia. The rest of the review of systems was unremarkable. The patient’s past medical history was only significant for hypertension, for which he took amlodipine, metoprolol, and olmesartan. Social history was remarkable for daily marijuana use which the patient described as “2-3 puffs” and daily alcohol consumption totaling 1 bottle of vodka weekly. The patient formerly smoked tobacco but had quit several decades prior. He was married and had adult children. His highest level of education completed was high school, and he had formerly worked in manufacturing but was retired. AC On physical examination, the patient’s vital signs were significant for an elevated blood pressure of 163/105 mm Hg. He appeared to be in no distress. Cardiac, pulmonary, and abdominal examinations were unremarkable. Neurologic examination did not demonstrate any cranial nerve, motor, or sensory deficits. There was no pronator drift. No dysmetria was apparent on finger to nose testing and gait was not ataxic. The patient was unable to solve basic mathematical problems including 9+9, 4x3, and 13-7. The patient's blood glucose was 109 mg/dL. Labs, including complete blood count, serum chemistry, and troponin I were all within normal limits. The patient’s electrocardiogram (EKG) was unchanged from previous. CT head demonstrated an area of hypodensity involving the left posterior parietal cortex and subcortical white matter consistent with a subacute infarct (Figure ACCEPTED MANUSCRIPT 1). No thrombolytics were administered. The patient was subsequently admitted for further evaluation. US CR IP T During his admission, the patient had a brain MRI which demonstrated an area of restricted diffusion involving the posterolateral left parietal lobe compatible with an acute infarct as well as several other smaller foci of diffusion restriction within the left occipital lobe, also compatible with acute infarcts (Figure 2). CTA head and neck demonstrated 40-50% stenosis of the left internal carotid artery. CT chest demonstrated a 4.2 cm ascending aortic aneurysm with scattered atherosclerotic plaque in the proximal aorta. Transesophageal echocardiogram revealed an atheroma measuring up to 7 mm in the descending aorta and preserved ejection fraction. Outpatient cardiac monitoring did not demonstrate any arrhythmias. Based upon his diagnostic tests, the most likely etiology of the patient’s stroke was felt to be an embolic event from the atherosclerotic plaque in his proximal aorta. On long-term follow-up with Neurology, the patient had ongoing mild acalculia and dysgraphia but was otherwise doing well, with no other neurological deficits or impairment. AN Discussion ED M In 1908, Lewandowsky and Stadelmann described the case of a patient who had difficulty performing calculations in the absence of a language disorder. This case established that calculation pathways in the brain are distinct from verbal pathways. The term alcalculia was first coined by Henschen in 19252,3. Later authors divided acalculia into 3 categories: alexia and agraphia for numbers, spatial disorganization of numbers, and anarithmetria or the isolated loss of calculation3. Additional classification systems have since been proposed. AC CE PT Acalculia may be from generalized CNS diseases such as dementia or localized diseases such as ischemic stroke or neoplasm1. The neural pathways involved in performing calculations are complex and not fully understood. Although acalculia is most commonly secondary to damage to the left parietal cortex, particularly the angular gyrus, it has been reported with lesions in other locations, including the thalamus, basal ganglia, left medial frontal lobe, and right parietal cortex2,4,5,6,7. Acalculia may manifest with the inability to distinguish numbers, place numbers in order, or perform basic calculations. It rarely occurs as an isolated deficit. Acalculia is also a component of Gerstmann syndrome, which is a tetrad of symptoms including finger agnosia, acalculia, dysgraphia, and left-right confusion8,9,10. Few studies have examined the prevalence of acalculia in patients presenting with stroke. In a prospective analysis of 194 patients with stroke, 59 (30.4%) had alexia, agraphia, acalculia, or different combinations of these disorders in addition to their other deficits11. Of these 59 patients, only 2 (3.4%) had Gerstmann syndrome. None had isolated acalculia or alexia. Current guidelines for the treatment of ischemic stroke recommend intravenous thrombolysis if the patient presents with sufficiently severe or disabling symptoms within 4.5 hours of onset provided no contraindications are present12. The NIH stroke scale (NIHSS) is suggested to ACCEPTED MANUSCRIPT IP T objectively assess the severity of stroke symptoms12. It assesses deficits in the patient’s level of alertness, speech, coordination, movement, and sensation. However, the NIHSS does not evaluate for deficits in higher cognitive functions such as calculation, reading, or writing. Therefore, patients presenting with these symptoms may not receive necessary testing or treatment for stroke and may not have appropriate follow up. It is important to assess for stroke in patients presenting with alexia, agraphia, or acalculia. Even if no abnormalities are apparent on initial examination or testing, admission for further evaluation including brain MRI should be strongly considered. At the very least, outpatient primary care physician or Neurology follow up with consideration of brain MRI is appropriate. Admission or outpatient follow up is critical to establish the diagnosis as well as assess for and treat modifiable risk factors for stroke. ED M AN US CR The prognosis of acalculia has been infrequently studied. A follow up study of 59 patients with alexia, agraphia, acalculia, or various combinations of these disorders conducted 24 months poststroke revealed that 37 (62.7%) died, 13 (22%) fully recovered, and 9 (15.3%) retained the same disorder or developed dementia or blindness13. Patients with combined language disorders had significantly higher mortality. The factors associated with recovery included initial severity of impairment, age, presence of neglect, and level of education. Conversely, other sources suggest that spontaneous recovery from acalculia often does occur within the first few months, even in severe cases14,15. Rehabilitation of acalculia consists of two strategies: regaining lost function and developing alternative strategies to compensate for the patient’s specific deficits16,17. Both rehabilitation strategies utilize the patient’s residual abilities as a starting point. Overall, despite the lower quality of evidence, present rehabilitation strategies appear to be effective for most patients. PT Conclusion AC CE Deficits such as alexia, agraphia, acalculia, or combinations thereof are not uncommon in patients presenting with stroke. Although these conditions are usually associated with more obvious motor, sensory, or speech deficits, they may rarely be the only symptom of stroke. The diagnosis of stroke must be considered in any patient experiencing an acute change in his or her ability to read, write, or perform basic mathematical calculations. Conversely, incorporating testing of reading, writing, and calculation ability into the neurological examination for patients presenting with altered mental status or stroke-like symptoms should be strongly considered. Occasionally, patients may present with more insidious and slowly progressive symptoms2. In conclusion, it is critical to consider the diagnosis of stroke in any patient presenting with acute changes in his or her ability to read, write, or perform basic mathematical calculations as these may be the only manifestations of stroke. ACCEPTED MANUSCRIPT References AC CE PT ED M AN US CR IP T 1. Bermejo-Velasco PE and Castillo-Moreno L. Acalculia: Classification, Etiology and Clinical Management. Rev Neurol. 2006 Aug 16-31; 43(4): 223-227. 2. Jensen M. The Accountant Who Lost Arithmetic: A Case Report of Acalculia with a Left Thalamic Lesion. J Med Cases. 2010 Dec 1; 1(3): 92–93. 3. Denburg N and Tranel D. Acalculia and Disturbances of the Body Schema. In: Heilman K and Valenstein E, editors. Clinical Neuropsychology. New York Oxford: 2003. 4. Mendez M et al. Thalamic Acalculia. J Neuropsychiatry and Clin Neurosciences. 2003 Feb 1; 15(1): 115-116. 5. Corbett AJ et al. Acalculia Following a Dominant-Hemisphere Subcortical Infarct. Arch Neurol. 1986 Sep; 43(9): 964-966. 6. Lucchelli F and De Renzi E. Primary Dyscalculia after a Medial Frontal Lesion of the Left Hemisphere. J Neurol Neurosurg Psychiatry. 1993 Mar; 56(3): 304–307. 7. Benavides-Varela S et al. Re-assessing Acalculia: Distinguishing Spatial and Purely Arithmetical Deficits in Right-hemisphere Damaged Patients. Cortex. 2017 Mar; 88: 151164. 8. Bhattacharyya S et al. Dyscalculia, Dysgraphia, and Left-Right Confusion from a Left Posterior Peri-Insular Infarct Behav Neurol. 2014; 2014: 823591. 9. Barbosa B et al. Gerstmann's Syndrome and Unilateral Optic Ataxia in the Emergency Department. Dement Neuropsychol. 2017 Oct-Dec; 11(4): 459–461. 10. Joao R et al. Transient Gerstmann Syndrome as Manifestation of Stroke: Case Report and Brief Literature Review. Dement Neuropsychol. 2017 Apr-Jun; 11(2): 202–205. 11. Zukic S et al. Gerstmann’s Syndrome in Acute Stroke Patients. Acta Inform Med. 2012 Dec; 20(4): 242–243. 12. Powers W et al. 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. 2018 Apr. 13. Zukic S et al. Two Year Outcomes of Post-stroke Writing and Reading Disorders. Appl Neuropsychol Adult. 2017 May 10: 1-5. 14. Caporali A et al. The Natural Course of Acalculia in Left-Brain-Damaged Patients. Neurol Sci. 2000 Jun; 21(3): 143-149. 15. Basso A et al. Spontaneous Recovery from Acalculia. J Int Neuropsychol Soc. 2005 Jan; 11(1): 99-107. 16. Rosselli M and Ardilla A. Rehabilitation of Calculation Disorders. In: Leon-Carrion J editor. Neuropsychological Rehabilitation: Fundamentals, Innovations, and Directions. Delray Beach GR/St. Lucie Press: 1997. 17. Cappa S et al. EFNS Guidelines on Cognitive Rehabilitation: Report of an EFNS Task Force. European J Neurol. 2005; 12: 665-680. ACCEPTED MANUSCRIPT Figure Legends Figure 1: Non-contrast CT head demonstrating hypodensity in the left parietal lobe compatible with subacute infarct. AC CE PT ED M AN US CR IP T Figure 2: Diffusion-weighted MRI brain demonstrating an area of restricted diffusion in the left parietal lobe consistent with acute infarct. Areas of restricted diffusion in the left occipital lobe not pictured. Figure 1 Figure 2