Neurocase, 2015 http://dx.doi.org/10.1080/13554794.2015.1031254
Spatial neglect in a patient with logopenic progressive aphasia Eduardo M. Zilli* and Kenneth M. Heilman Department of Neurology, University of Florida College of Medicine, The Center for Neuropsychological Studies, and the Veterans Affairs Medical Center, Gainesville, FL, USA (Received 4 November 2014; accepted 15 March 2015) Spatial neglect and extinction are induced by posterior superior temporal and inferior parietal dysfunction. In patients with logopenic progressive aphasia (LPA) these structures are often degenerated, but there are no reports of these disorders being associated. A 53-year-old man with the signs of LPA revealed right-sided spatial neglect on line bisection and drawing tests as well as multimodal extinction. MRI showed left hemispheric posterior temporoparietal atrophy. Since injury to the core structures for these aphasic and attentional syndromes overlaps, patients with LPA should be screened for spatial neglect and extinction. Keywords: logopenic progressive aphasia; spatial neglect; dementia; screening; extinction
Background Spatial neglect has been deﬁned as a failure to report, respond, or orient to stimuli that are presented in a speciﬁc location, provided that this failure is not due to elementary sensory or motor disorders (Heilman & Valenstein, 1979). Neglect can be described in relation to frames of reference, such as allocentric, or object-based, as well as egocentric, or viewer-based (Pizzamiglio, Guariglia, & Cosentino, 1998). Clinical studies with stroke patients and ablative studies in monkeys suggest that spatial neglect can be associated with lesions to several cerebral structures. At the cortical level, critical lesions have been reported in the posterior temporo-parietal junction and posterior parietal cortex (Heilman & Valenstein, 1979; Mesulam, 1999) including the angular gyrus (Mort et al., 2003), supramarginal gyrus (Doricchi & Tomaiuolo, 2003), the superior temporal gyrus (Karnath, Ferber, & Himmelbach, 2001) as well as the insula (Karnath, Fruhmann Berger, Küker, & Rorden, 2004). Medina et al. (2009) noticed that injury to the right supramarginal gyrus was most predictive of neglect. Injuries to the lateral frontal cortex, as well as the anterior cingulate gyrus, have also been reported to be associated with neglect (Heilman & Valenstein, 1972). At the subcortical level, damage to the thalamus (Watson & Heilman, 1979), basal ganglia (Vallar & Perani, 1986), and mesencephalic reticular formation (Watson, Heilman, Miller, & King, 1974) may also produce neglect. Lesions in the subcortical white matter around the frontal,
temporal, and parietal lobes have been described as producing neglect (Doricchi & Tomaiuolo, 2003); more recently, Urbanski et al.(2011) studied 12 patients with right hemisphere lesions with diffusion tensor imaging tractography, and showed that the six patients with neglect had lesions of the anterior limb of the internal capsule and in the white matter underlying the inferior frontal gyrus. With regard to the anatomical correlations of neglect subtypes, Medina et al. (2009), as well as Verdon, Schwartz, Lovblad, Hauert, and Vuilleumier (2010), provided evidence that injury to portions of the dorsal visual processing stream, including the inferior parietal lobe, is associated with spatial neglect in egocentric (viewer-centered) coordinates, whereas injury to parts of the ventral visual processing stream found in the temporal lobe is associated with allocentric (object-centered) spatial neglect. Chechlacz et al. (2010), however, suggested that there may be an anterior–posterior dichotomy, with anterior lesions being associated with egocentric neglect and more posterior cortical damage being associated with allocentric neglect. Neurodegenerative diseases have also been associated with spatial neglect. Mendez, Cherrier, and Cymerman (1997) reported right and left spatial neglect in 15 patients with Alzheimer disease. Ishiai, Okiyama, Koyama, and Seki (1996) described a patient with probable Alzheimer disease and hypometabolism in the right temporoparietal regions, who showed a rightward bias on a line bisection task. Bartolomeo et al. (1998) described a patient with
*Corresponding author. Email: [email protected]
ﬂ.edu The reader will beneﬁt from reading this article by acquiring increased awareness for the possibility of comanifestation of progressive aphasias and visual neglect, as well as enhanced understanding of its neurobiological underpinnings; the article’s main clinical implication is the advocation of routine neglect screening in progressive aphasias. © 2015 Taylor & Francis
E.M. Zilli and K.M. Heilman
dementia of Alzheimer’s type, who had left posterior parietal atrophy and reduced blood ﬂow to the left temporo-parietoccipital area on single-photon emission computed tomography, with right-sided neglect on the line bisection, copying and cancellation tasks, as well as visual and tactile extinction to simultaneous stimuli. Silveri, Ciccarelli, and Cappa (2011) reported right allocentric neglect in a patient with corticobasal syndrome and left parietoocccipital atrophy, as well as left egocentric neglect in three patients with right hemisphere posterior cortical atrophy, and right motor-executive neglect in a patient with left frontal atrophy. Zilli and Heilman (2015) reported a patient with posterior cortical atrophy, left parietal atrophy, and allocentric neglect. To our knowledge, however, there have been no reports of patients with the signs associated with logopenic progressive aphasia (LPA) and spatial neglect. LPA is a neurodegenerative disease characterized by decreased speech rate with long word-ﬁnding pauses and impairment in phonological loop functions, moderate deficits in naming with relative preservation of semantics, impaired repetition, and comprehension for complex sentences (Gorno-Tempini et al., 2008). It has been associated with atrophy and/or hypometabolism in the left inferior parietal lobe, as well as in the superior and middle temporal gyri. Since injury to the temporal and parietal lobes is often associated with signs of spatial neglect, it is surprising that spatial neglect and/or extinction to simultaneous stimulation have not been noted to coexist with the signs associated with LPA; the purpose of this report is to describe a patient with a progressive aphasia akin to LPA, accompanied by spatial neglect and extinction.
Case presentation History This 53-year-old right-handed bilingual man, who was ﬂuent in both English and Spanish, with 16 years of education, was referred to our clinic for evaluation. He had had about 2 years of cognitive deﬁcits, the most prominent of which involved speech and language. The ﬁrst problem noted was a decline in his efﬁciency at his ofﬁce job, with speciﬁc difﬁculties with calculations and sustained attention. After a few months his speech became involved, with impaired word ﬁnding and naming, production of frequent phonemic paraphasic errors, and reduction in speech ﬂuency, including overall output and sentence length. He continued to decline cognitively, developing progressive difﬁculties following multistep commands, reading and writing, as well as planning future activities. He had a motor vehicle accident (hit a gas station bar), but did not stop driving. Prior to our clinic evaluation he had an extensive laboratorial evaluation, which was unremarkable.
General, physical, and neurological examination His general physical examination was unremarkable, as was his general neurological examination, with normal cranial nerve function, normal strength, bulk, and tone. He had an equivocal right pronator drift, but no abnormal movements. His coordination, reﬂexes, and gait were normal. He had no bradykinesia. While the patient revealed no evidence of a severe sensory loss, in light of his language impairment, detailed sensory testing could not be performed, as he would respond inconsistently or not at all to questions presented to him as part of the sensory exam. For example, when asked whether the stimulus touching him was sharp or dull, he would respond “yes” to all stimuli even after multiple repetitions of the command. In contrast, he would answer yes or no reliably when asked whether he was being touched.
Neurobehavioral testing The patient was alert and cooperative. His score on the Mini-Mental Status Exam (Folstein, Folstein, & McHugh, 1975) was 9; he lost points for season, day of the week, county, city, ﬂoor, 2 points for registration (it took him three trials to register all three words), 5 for attention and calculation, 2 for word recall, 1 for naming (resorted to circumlocution), 1 for repetition (“No ifs, buts and what.”), 2 points for his inability to follow multistep commands, 1 for reading and not following the written command, 1 for writing a sentence (wrote a single word; he was able to write a complete sentence when requested again, though), and 1 for copying the design. He was able to name the current and past four presidents of the USA. He was able to comprehend simple commands, and his verbal ﬂuency was decreased, with abundant word-ﬁnding pauses. In addition, he was unable to give any signiﬁcant details on well-known stories such as “Cinderella” or the Nativity. His automatic speech was tested by asking him to recite the Lord’s prayer and this was also impaired. Repetition was impaired for long, compound sentences, such as those used in the Montreal Cognitive Assessment (MoCA), and for sentences rich in function words, but not for single words or simple sentences (with a subject–verb– object structure). On a naming to confrontation task using the short form of the Boston Naming Test (Kaplan, Goodglass, & Weintraub, 2001), he made three phonemic paraphasic errors; he also misidentiﬁed a tripod for a needle (although he was able to correctly pick the correct word when presented to him together with three other words). He could not name the Sphinx but knew it was located in Egypt; however, he pointed to the word “pyramid.” He called the beaver an “otter.” He was able to read out loud, but could not follow printed commands. He did have marked difﬁculties reading nonwords. He could write
Neurocase Table 1.
Language tests. Spontaneous ﬂuency
Impaired, frequent word-ﬁnding pauses
Boston Naming Test 8/15 correct
a simple, grammatically correct sentence. He also correctly interpreted a sentence in the passive voice (Table 1). His performance on the Hopkins Verbal Learning Test (Brandt, 1991) was impaired. In the learning portion, of the 12 words presented he was able to only immediately name two on the ﬁrst trial, and one word on both the second and third trials; furthermore, he had a commission error, which he repeated in all trials. After a 20-minute delay he did not spontaneously recall any of the 12 words presented. Although he correctly identiﬁed 7/12 words in the forced recognition part of the test, he also gave 10 false-positive answers (Table 2). He was able to recall 1/3 of the words he was told to remember in the registration part of the Mini-Mental Status Exam (the same word he was able to remember after the ﬁrst trial). When copying the intersecting pentagons from the Mini-Mental Status Exam, his pentagons touched but did not intersect, and their proportions were altered as well. He showed even more difﬁculties when drawing them from memory, as the pentagon shape was lost. He could not copy a cube properly and, when asked to draw a clock, he could draw a circle, but with no numbers or hands. He was able to ﬁnd 2/3 of the items hidden in the clinic room in his presence after about 10 minutes, during which time he was distracted by performing other tasks. He had no signiﬁcant difﬁculties localizing 5 out of 5 states in an outline map of the USA. He had dyscalculia and mild right–left confusion, but not ﬁnger agnosia. He was unable to perform correctly at the Trails-B version in the MoCA test (seemingly ignoring the letters and connecting only the numbers). He also was very impaired on Luria’s (1970) ﬁst-edge–palm test and could not inhibit the prepotent ipsilateral responses in the crossed response task when his eyes were closed and he was asked to raise the arm contralateral to the one being touched. His working memory and letter ﬂuency were also impaired (Table 3). His category ﬂuency was very impaired (5 for animals). He had difﬁculties with abstract thinking, as assessed by the similarities test in the MoCA battery. For buccofacial apraxia testing, he was verbally asked to
blow a kiss, and could correctly perform this action. Nevertheless, he showed clear evidence of bilateral ideomotor apraxia when asked to demonstrate how to brush his teeth, or to pantomime using a pair of scissors to cut a piece of paper. He had, however, no problems demonstrating how to use a hammer.
Tests of spatial neglect and inattention The patient was screened for egocentric spatial neglect with the task of attempting to bisect a 17.7-cm-long horizontally oriented line. He had a 1.6 cm leftward deviation from its true center, for a mean leftward bias of 18.08%. To further assess this bias, he performed six line bisection trials with a 24.1-cm-long horizontally oriented line. On this task he had a mean leftward bias of 18.11%. Fujii, Fukatsu, Yamadori, & Kimura (1995) tested 36 normal participants who were a mean of 70 years old on the line bisection task, and found at the 95% conﬁdence interval errors range between –5.68% to the left and +7.64% to the right. Thus, this patient’s line bisection was clearly abnormal and indicative of right-sided spatial neglect. On a letter “A” cancellation task with letter foils (Doty, Bowers, & Heilman, 1990) he was able to cancel all 10 letter “A” targets. To determine whether this patient had stimulus-centered neglect, he was assessed with a gap detection cancellation test, in which 42 small squares (2 × 2 cm) were distributed on an A4 sheet with 14 squares having an opening gap on the left side and 14 with the gap on the right side. The open squares were pseudorandomly distributed over the entire page. He missed three of the seven squares with gaps on the left side of the square, which were on the right side of the paper, and close to its middle. He also missed one square with a gap on the right that was on the far left aspect of the paper (Figure 1, Table 4). When copying a modiﬁed Ogden scene (Ogden, 1985), he did not draw the house, the tree, or the sun, all of which were on the right side of the picture (Figure 2), whereas he did not omit any of the elements portrayed on left side of the picture (cloud, tree, fence). This further substantiates a
Hopkins immediate recall 4/36
Hopkins free recall
Hopkins forced recognition
Long-term recall from MMSE
7/12; discriminating index: 3
4 Table 3.
E.M. Zilli and K.M. Heilman Executive function tests.
Letter ﬂuency 0-0-1
Contralateral response inhibition
4 (forward), 2 (backward)
deﬁcit in right-sided viewer-centered allocation of attention. Based on Azouvi et al. (2006)’s description of the performance of normal individuals on the Ogden test, the omission of even one element would be sufﬁcient to put him in the abnormal range. In addition, his drawing of the fence from that picture, to which he added a third horizontal line, was suggestive of perseveration.
supramarginal gyrus, and transverse temporal gyrus, as well as the parietal operculum. There was also atrophy of the middle frontal gyrus bilaterally, and mild periventricular leukoaraiosis, that was most prominent in the superior fronto-occipital fasciculus.
Discussion Brain imaging This patient had magnetic resonance imaging of his brain performed within a few days of his appointment at our clinic (Figure 3a–f). The images revealed atrophy of portions of the left hemisphere, including the superior temporal gyrus, postcentral gyrus, planum temporale,
Our patient demonstrated dysfunction of his speech-language networks, including impairments of word ﬁnding, naming, and, when speaking, the production of phonemic paraphasic errors. He also showed impaired repetition, with an accompanying working memory deﬁcit. His phonological loop dysfunction, which can impair working memory and comprehension of complex commands, was
Figure 1. Patient’s performance at the gap-detection cancellation task. He missed three of the seven squares with gaps on the left that were on the right side of the paper, and one square with a gap on the right that was on the far left aspect of the paper, but did not miss any square with a left-sided opening on the left side of the page, and missed no squares with right-sided openings on the right side of the page.
Neurocase Table 4. Line bisection Right neglect
Neglect tests. Cancellation Normal performance
Gap detection Missed 3/7 targets with gap on R, 1/7 on L
Figure 2. Patient’s attempt to copy Ogden’s ﬁgure: he omitted the house, the tree, and the sun, all of which were on the right side of the picture.
likely related to his difﬁculties reliably participating in a detailed sensory examination, as well as executing multiple-step commands. Although his impairments were not strictly conﬁned within the language domain, his speechlanguage deﬁcits were the same as those reported with LPA, as described by Gorno-Tempini et al. (2011). Pathological ﬁndings characteristic of Alzheimer’s disease are often associated with the LPA syndrome. For example, Harris et al. (2013) described 13 patients with this syndrome, seven of whom had Alzheimer’s pathology. In a report by Mesulam et al. (2014) 56% of 32 patients with LPA had Alzheimer’s pathology. Josephs et al. (2013) described increased density of neuroﬁbrillary tangles in left temporoparietal cortices in patients with LPA when compared with patients with dementia of Alzheimer’s type who are without the signs of LPA, but found no differences in the hippocampi. Mahoney et al. (2013) performed diffusion-tensor imaging tractography on 10 patients with LPA, ﬁnding bilateral alterations, although more prominent on the left, with the inferior longitudinal fasciculus, crucial for lexical retrieval, being signiﬁcantly involved. The superior longitudinal fasciculus, uncinate fasciculus, and subcortical projections were also affected. This patient’s language impairments interfered with testing of
Extinction R to simultaneous visual or tactile stimuli
other domains, such as memory, to an extent that the interpretation of the results of tests that depend on language was rendered extremely challenging, so that evaluating him for mesial temporal or diencephalic dysfunction was also very difﬁcult. This man also had evidence of executive dysfunction, as indicated by his impairments in inhibition of prepotent responses on the crossed response task, in his inability to perform abstract thinking (on the MoCA similarities subtest), his failure to disengage (as shown by his pattern in the MoCA Trails B test), his impairments in action sequencing (ﬁst-edge–palm), and the element of perseveration in the Ogden ﬁgure. Na et al. (1999) have shown motor perseveration in 30% of a sample of 60 patients with left hemispatial neglect from a right hemispheric stroke, and posited that this perseverative behavior might be related to aberrant approach behaviors from frontal lobe injury, which is often associated with an attentional or intentional bias toward the ipsilesional targets. Teichmann et al. (2013) studied 19 patients with LPA, whose performance on the Frontal Assessment Battery was almost two standard deviations below normal, illustrating that executive dysfunction can be quite prominent in patients with this LPA syndrome. Unfortunately, since language disorders may interfere with valid testing of frontal-executive functions, many studies do not report any executive function measures for patients with LPA (or perform a very limited number of tests, such as Rohrer et al., 2013), making it difﬁcult to estimate its real prevalence. Our patient’s acquired difﬁculty with left–right confusion and calculations, elements of the Gerstmann syndrome, provides evidence for left parietal dysfunction (Levin & Spiers, 1985), as does his bimanual ideomotor apraxia (Heilman, Rothi, & Valenstein, 1982). Ideomotor apraxia has been described in association with the progressive aphasias (e.g., Funayama et al., 2013). In patients with LPA, apraxia does not seem not to be quite as profound as in the agrammatic variant of primary progressive aphasia (Adeli, Whitwell, Duffy, Strand, & Josephs, 2013), and patients with LPA often have a pattern similar to that which our patient demonstrated. For example, our patient appeared to be more impaired in the more complex praxis tasks, such as pantomiming the use of scissors to cut a piece of paper in half, compared to praxis tasks with reduced degrees of freedom, such as pretending to use a hammer.
E.M. Zilli and K.M. Heilman
Figure 3. Selected brain MRI slices from the patient obtained days before his evaluation. Figure 3a–c are FLAIR transverse cuts, 3d is a T1 left sagittal cut, and 3e–f are coronal T2 based.
Buxbaum and Kalénine’s (2010) “Two Action Systems” postulate suggests a differentiation between structure- and function-based actions. According to their
framework, the left hemisphere’s ventral-dorsal system is important for the programing, storing, and recognition of the core features of object-related actions, thereby
Neurocase permitting the identiﬁcation of a gesture such as “cutting” regardless of the plane, amplitude, or grip with which the action is performed. While gesture recognition was not tested in our patient, his performance when asked to pantomime the utilization of tools suggests that his ventral-dorsal system is dysfunctional. In contrast, the bilateral dorso-dorsal system is important for planning and execution of structure-based movements, permitting the acquisition of visualized information about object shape, size, and location. Bilateral damage to this dorsal-dorsal system may lead to disorders such as optic ataxia, in which a patient may be impaired at directing their forelimb to the location of the object that is the target of this action. This system seems to have been relatively spared in our patient, since he made no errors of that type. This patient’s performance on the clock-drawing test and ﬁgure-copying tasks was also impaired. It has been shown that frontal-executive dysfunction can be a major cause for impairments in tasks such as clock drawing (Cosentino, Jefferson, Chute, Kaplan, & Libon, 2004). However, these impairments in drawing and copying raise concern for the presence of visuospatial dysfunction. Whereas constructional apraxia may also be seen with left parietal dysfunction (Chechlacz et al., 2014), these features might bring to mind the well-documented association between progressive aphasias, LPA in particular, and posterior cortical atrophy (Magnin et al., 2013). In a recent report, for example, Wicklund et al. (2013) diagnosed two patients, presenting with logopenic-type aphasia, as having posterior cortical atrophy. This diagnosis was, in part, based on their visual spatial dysfunction and their ﬂuorodeoxyglucose PET imaging, which revealed prominent hypometabolism in the left occipitotemporal region. The diagnostic criteria for posterior cortical atrophy, as reviewed by Crutch et al. (2012), include visual disorders such as visual agnosia, simultanagnosia, optic ataxia, and ocular apraxia. Our patient revealed none of these visual disorders. In addition, he had evidence of executive dysfunction, as well as atrophy of the posterior superior temporal and inferior parietal lobes. This absence of the signs associated with posterior cortical degeneration and presence of the signs associated with left temporoparietal dysfunction led us into classifying his impairment as a form of LPA. Some of the features that this patient displayed, such as the degree of executive dysfunction and the low score on the MMSE, suggest a more advanced stage than what has been typically reported in patients with LPA; however, the diagnosis of LPA is consistent with the criteria of Gorno-Tempini et al. (2011), as he met the two core and all four auxiliary criteria, as well as having the characteristic imaging changes. Unlike “classic” cases of LPA, his symptoms were not conﬁned to the language domain; however, the overlap between the critical structures found to be involved in LPA with those related to spatial neglect permits the inference that other
patients with signs of LPA may reveal similar visuospatial disorders if sufﬁciently tested. One possible reason for this disparity between our patient and prior reports of LPA may be selective reporting, such that that the authors of some of the published papers on this subject focus on the language speech disorders (e.g., see Leyton et al., 2011). It is also possible that there could be different subtypes of patients with LPA, in light of the discrepant clinical courses that have been reported by different authors: both rapid decline, with more diffuse cognitive impairment than seen with other progressive aphasias (Leyton, Hsieh, Mioshi, & Hodges, 2013), and relative stability (Mesulam et al., 2014) have been described. The presence of executive dysfunction, as reported by Teichmann et al. (2013), could be another distinguishing factor in subtyping this disorder. If this impression is accurate, reﬁnement in existing criteria would be required for adequately discriminating these different forms or subtypes of LPA. In addition to this patient’s prominent language and frontal-executive dysfunction, he also demonstrated rightsided egocentric (viewer-centered) neglect, with consistent and excessive leftward deviation on line bisection tasks and omission of entire elements on the right side when attempting to draw the modiﬁed Ogden ﬁgure. He also omitted three objects with left-sided gaps in the gap detection cancellation test, suggesting the presence of an allocentric or object-centered element to his attentional impairment, possibly related to posterior right hemispheric dysfunction (Chechlacz et al., 2010). The fact that this patient’s allocentric (object-centered) omissions were all close to midline, with none at the rightmost aspect of the paper sheet, cannot be fully accounted for by the hypothesis of a gradient of attentional dysfunction toward the right side. A more promising explanation would be that the allocation of right versus left egocentric attention inﬂuences the allocation of object or allocentric attention. This hypothesis, however, will have to be explored in further studies. This patient also demonstrated right-sided extinction to bilateral simultaneous visual and tactile stimuli. Extinction can be characterized as a disorder of lateral attention in which there is a bias for attending to stimuli presented on the ipsilateral side at the expense of items on the contralateral side (Heilman & Valenstein, 1979). In a study of 50 patients with chronic neglect, Chechlacz et al. (2013) described right visual extinction to be associated with lesions in several areas of the left cerebral hemisphere, but the temporoparietal junction and superior longitudinal fasciculus were deemed to have a critical role in the cooccurrence of these phenomena. Regarding the character of the spatial bias detected in patients with spatial neglect, inattention to the right side has been described less often and is typically less severe
E.M. Zilli and K.M. Heilman
than left spatial neglect (Weintraub, Daffner, Ahern, Price, & Mesulam, 1996). In Suchan and Karnath’s study (2011) of patients with unilateral left-sided stroke, 17 out of 424 patients were found to have spatial neglect with cancellation and copying tasks. In this study, the areas found to be most strongly associated with right-sided neglect included the superior temporal gyrus, medial temporal gyrus, inferior parietal lobe, and insula. All the patients with neglect also had aphasia. The regions affected in right hemispatial neglect associated with left brain damage seemed to be homologous to the ones damaged in patients with left hemispatial neglect due to right brain damage. That association is also present for white matter tracts, including the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and the superior fronto-occipital fasciculus. Maeshima, Shigeno, Dohi, Kajiwara, and Komai (1992) also reported right-sided neglect to be associated with left hemisphere temporal, parietal, and occipital lobe lesions. Beis et al. (2004) studied 78 patients who suffered leftsided strokes, 43.5% of whom showed neglect, which was most common with damage to the posterior association cortex. The frequency of neglect after right-sided lesions was, however, approximately two times greater than with left-sided lesions, although 12.3% of the patients with left hemisphere lesions were excluded due to severe aphasia. Regarding the hemispheric asymmetry associated with neglect, Weintraub, Daffner, Ahern, Price and Mesulam. (1996) reported that right-sided visual hemispatial inattention occurred with greater frequency and severity in patients with bilateral lesions than in patients with unilateral left-sided lesions. The purported mechanism to account for those ﬁndings is based on the theory that the right hemisphere’s attentional networks can be directed to both the ipsilateral and contralateral hemispaces, whereas the left hemisphere’s homologous networks can only direct attention to the contralateral hemispace (Heilman & Van Den Abell, 1980). The manifestation of right-sided spatial neglect would therefore be explained by the presence of lesions in the left hemisphere’s attention network, together with partial deterioration of the right hemisphere’s attentional network, which would compromise its ability to allocate attention to the right hemispace while preserving at least some attentional function in the left hemispace. As mentioned, LPA is often associated with the pathology of Alzheimer’s disease, and although our patient’s magnetic resonance imaging showed evidence of involvement in key cortical and white matter structures implicated in LPA and an egocentric visuospatial neglect, it is very possible that this patient also had some degenerative changes in his right posterior temporoparietal regions. Spatial neglect and extinction to simultaneous stimuli can be deleterious and even dangerous disabilities (as possibly illustrated by our patient’s automobile accident). Unfortunately, patients with LPA are not routinely assessed for these disorders. This overlap among LPA,
spatial neglect, and extinction, which can be predicted when the core structures associated with those syndromes are considered, suggests that patients with LPA be routinely screened for spatial neglect and extinction, especially given the plethora of adverse consequences of not detecting these attentional disorders and the possibility that these attentional deﬁcits can be managed and rehabilitated (Riestra & Barrett, 2013). Performing a battery of tests including line bisection, gap detection, copying of a complex scene, and target cancellation, together with simultaneous visual and tactile stimuli would be an efﬁcient way of evaluating these disorders.
Disclosure statement No potential conﬂict of interest was reported by the authors.
Funding Supported in part by the State of Florida, Department of Elder Affairs.
References Adeli, A., Whitwell, J. L., Duffy, J. R., Strand, E. A., & Josephs, K. A. (2013, January, June 29). Ideomotor apraxia in agrammatic and logopenic variants of primary progressive aphasia. Journal of Neurology, 260, 1594–1600. doi:10.1007/s00415013-6839-9 Azouvi, P., Bartolomeo, P., Beis, J. M., Perennou, D., PradatDiehl, P., & Rousseaux, M. (2006). A battery of tests for the quantitative assessment of unilateral neglect. Restorative Neurology and Neuroscience, 24, 273–285. Bartolomeo, P., Dalla Barba, G., Boissé, M. F., Bachoud-Lévi, A. C., Degos, J. D., & Boller, F. (1998). Right-side neglect in Alzheimer’s disease. Neurology, 51, 1207–1209. doi:10.1212/WNL.51.4.1207 Beis, J. M., Keller, C., Morin, N., Bartolomeo, P., Bernati, T., Chokron, S., & Azouvi, P. (2004). Right spatial neglect after left hemisphere stroke: Qualitative and quantitative study. Neurology, 63, 1600–1605. doi:10.1212/01.WNL.00001 42967.60579.32 Brandt, J. (1991). The Hopkins verbal learning test: Development of a new memory test with six equivalent forms. Clinical Neuropsychologist, 5, 125–142. doi:10.1080/13854049108403297 Buxbaum, L. J., & Kalénine, S. (2010, March). Action knowledge, visuomotor activation, and embodiment in the two action systems. Annals of the New York Academy of Sciences, 1191, 201–218. doi:10.1111/ j.1749-6632.2010.05447.x Chechlacz, M., Novick, A., Rotshtein, P., Bickerton, W. L., Humphreys, G. W., & Demeyere, N. (2014, December). The neural substrates of drawing: A voxel-based morphometry analysis of constructional, hierarchical, and spatial representation deﬁcits. Journal of Cognitive Neuroscience, 26, 2701–2715. doi:10.1162/jocn_a_00664 Chechlacz, M., Rotshtein, P., Bickerton, W., Hansen, P. C., Deb, S., & Humphreys, G. W. (2010). Separating neural correlates of allocentric and egocentric neglect: Distinct cortical sites and common white matter disconnections. Cognitive
Neurocase Neuropsychology, 27, 277–303. doi:10.1080/ 02643294.2010.519699 Chechlacz, M., Rotshtein, P., Hansen, P. C., Deb, S., Riddoch, M. J., & Humphreys, G. W. (2013, February). The central role of the temporo-parietal junction and the superior longitudinal fasciculus in supporting multi-item competition: Evidence from lesion-symptom mapping of extinction. Cortex, 49, 487–506. doi:10.1016/j.cortex.2011.11.008 Cosentino, S., Jefferson, A., Chute, D. L., Kaplan, E., & Libon, D. J. (2004, June). Clock drawing errors in dementia: Neuropsychological and neuroanatomical considerations. Cognitive and Behavioral Neurology, 17, 74–84. doi:10.1097/01.wnn.0000119564.08162.46 Crutch, S. J., Lehmann, M., Schott, J. M., Rabinovici, G. D., Rossor, M. N., & Fox, N. C. (2012). Posterior cortical atrophy. The Lancet Neurology, 11, 170–178. doi:10.1016/ S1474-4422(11)70289-7 Doricchi, F., & Tomaiuolo, F. (2003). The anatomy of neglect without hemianopia: A key role for parietal-frontal disconnection? Neuroreport, 14, 2239–2243. doi:10.1097/ 00001756-200312020-00021 Doty, L., Bowers, D., & Heilman, K. M. (1990). Florida mental status exam for progressive dementia screening. The Gerontologist, Abstract for Poster Session Presentation 30, 20A. Folstein, M., Folstein, S. E., & McHugh, P. R. (1975). “ Mini Mental State ”A Practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198. Fujii, T., Fukatsu, R., Yamadori, A., & Kimura, I. (1995). Effect of age on the line bisection test. Journal of Clinical and Experimental Neuropsychology, 17, 941–944. doi:10.1080/ 01688639508402443 Funayama, M., Nakagawa, Y., Yamaya, Y., Yoshino, F., Mimura, M., & Kato, M. (2013, November 1). Progression of logopenic variant primary progressive aphasia to apraxia and semantic memory deﬁcits. BMC Neurol, 13, 158. doi:10.1186/1471-2377-13-158 Gorno-Tempini, M. L., Brambati, S. M., Ginex, V., Ogar, J., Dronkers, N. F., Marcone, A., & Miller, B. L. (2008, October 14). The logopenic/phonological variant of primary progressive aphasia. Neurology, 71, 1227–1234. doi: 10.1212/01.wnl.0000320506.79811.da Gorno-Tempini, M. L., Hillis, A. E., Weintraub, S., Kertesz, A., Mendez, M., Cappa, S. F., & Grossman, M. (2011, March 15). Classiﬁcation of primary progressive aphasia and its variants. Neurology, 76, 1006–1014. doi:10.1212/ WNL.0b013e31821103e6 Harris, J. M., Gall, C., Thompson, J. C., Richardson, A. M., Neary, D., Du Plessis, D., & Jones, M. (2013, November 19). Classiﬁcation and pathology of primary progressive aphasia. Neurology, 81, 1832–1839. doi:10.1212/01.wnl.0000436070. 28137.7b Heilman, K. M., Rothi, L. J. G., & Valenstein, E. (1982). Two forms of ideomotor apraxia. Neurology, 32, 342–342. doi:10.1212/WNL.32.4.342 Heilman, K. M., & Valenstein, E. (1972, June). Frontal lobe neglect in man. Neurology, 22, 660–660. doi:10.1212/ WNL.22.6.660 Heilman, K. M., & Valenstein, E. (1979). Mechanisms underlying hemispatial neglect. Annals of Neurology, 5, 166–170. doi:10.1002/ana.410050210 Heilman, K. M., & Van Den Abell, T. (1980). Right hemisphere dominance for attention: The mechanism underlying
hemispheric asymmetries of inattention (neglect). Neurology, 30, 327–327. doi:10.1212/WNL.30.3.327 Ishiai, S., Okiyama, R., Koyama, Y., & Seki, K. (1996). Unilateral spatial neglect in Alzheimer’s disease. Acta Neurologica Scandinavica, 93, 219–224. doi:10.1111/ j.1600-0404.1996.tb00204.x Josephs, K. A., Dickson, D. W., Murray, M. E., Senjem, M. L., Parisi, J. E., Petersen, R. C., & Whitwell, J. L. (2013, November). Quantitative neuroﬁbrillary tangle density and brain volumetric MRI analyses in Alzheimer’s disease presenting as logopenic progressive aphasia. Brain and Language, 127, 127–134. doi:10.1016/j.bandl.2013.02.003 Kaplan, E. F., Goodglass, H., & Weintraub, S. (2001). The Boston naming test (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins. Karnath, H.-O., Ferber, S., & Himmelbach, M. (2001). Spatial awareness is a function of the temporal not the posterior parietal lobe. Nature, 411, 950–953. doi:10.1038/35082075 Karnath, H. O., Fruhmann Berger, M., Küker, W., & Rorden, C. (2004). The anatomy of spatial neglect based on voxelwise statistical analysis: A study of 140 patients. Cerebral Cortex, 14, 1164–1172. doi:10.1093/cercor/bhh076 Levin, H. S., & Spiers, P. A. (1985). Acalculia. In K. M. Heilman & E. Valenstein (Eds.), Clinical neuropsychology (pp. 97– 114). New York, NY: Oxford University Press. Leyton, C. E., Hsieh, S., Mioshi, E., & Hodges, J. R. (2013). Cognitive decline in logopenic aphasia: More than losing words. Neurology, 80, 897–903. doi:10.1212/ WNL.0b013e318285c15b Leyton, C. E., Villemagne, V. L., Savage, S., Pike, K. E., Ballard, K. J., Piguet, O., & Hodges, J. R. (2011). Subtypes of progressive aphasia: Application of the international consensus criteria and validation using - amyloid imaging. Brain, 134, 3030–3043. doi:10.1093/brain/awr216 Luria, A. R. (1970). Traumatic aphasia: Its syndromes, psychology and treatment. (D. Bowden, Trans.) The Hague: Mouton. Maeshima, S., Shigeno, K., Dohi, N., Kajiwara, T., & Komai, N. (1992, June). A study of right unilateral spatial neglect in left hemispheric lesions: The difference between right-handed and non-right-handed post-stroke patients. Acta Neurologica Scandinavica, 85, 418–424. doi:10.1111/ j.1600-0404.1992.tb06040.x Magnin, E., Sylvestre, G., Lenoir, F., Dariel, E., Bonnet, L., Chopard, G., & Rumbach, L. (2013, February). Logopenic syndrome in posterior cortical atrophy. Journal of Neurology, 260, 528–533. doi:10.1007/s00415-012-6671-7 Mahoney, C. J., Malone, I. B., Ridgway, G. R., Buckley, A. H., Downey, L. E., Golden, H. L., & Warren, J. D. (2013, June). White matter tract signatures of the progressive aphasias. Neurobiology of Aging, 34, 1687–1699. doi:10.1016/j. neurobiolaging.2012.12.002 Medina, J., Kannan, V., Pawlak, M. A., Kleinman, J. T., Newhart, M., Davis, C., & Hillis, A. E. (2009). Neural substrates of visuospatial processing in distinct reference frames: Evidence from unilateral spatial neglect. Journal of Cognitive Neuroscience, 21, 2073–2084. Mendez, M. F., Cherrier, M. M., & Cymerman, J. S. (1997, July). Hemispatial neglect on visual search tasks in Alzheimer’s disease. Neuropsychiatry Neuropsychol Behav Neurol, 10, 203–208. Mesulam, M.-M. (1999). Spatial attention and neglect: Parietal, frontal and cingulate contributions to the mental representation and attentional targeting of salient
E.M. Zilli and K.M. Heilman
extrapersonal events. Philosophical Transactions of the Royal Society B: Biological Sciences, 354, 1325–1346. doi:10.1098/rstb. 1999.0482 Mesulam, M. M., Weintraub, S., Rogalski, E. J., Wieneke, C., Geula, C., & Bigio, E. H. (2014). Asymmetry and heterogeneity of Alzheimer’s and frontotemporal pathology in primary progressive aphasia. Brain, 137, 1176–1192. doi:10.1093/brain/awu024 Mort, D. J., Malhotra, P., Mannan, S. K., Rorden, C., Pambakian, A., Kennard, C., & Husain, M. (2003). The anatomy of visual neglect. Brain, 126, 1986–1997. doi:10.1093/brain/awg200 Na, D. L., Adair, J. C., Kang, Y., Chung, C. S., Lee, K. H., & Heilman, K. M. (1999, May 12). Motor perseverative behavior on a line cancellation task. Neurology, 52, 1569–1569. 10.1212/WNL.52.8.1569 Ogden, J. A. (1985). Anterior-posterior interhemispheric differences in the Loci of lesions producing visual hemineglect. Brain and Cognition, 4, 59–75. doi:10.1016/0278-2626(85)90054-5 Pizzamiglio, L., Guariglia, C., & Cosentino, T. (1998). Evidence for separate allocentric and egocentric space processing in neglect patients. Cortex, 34, 719–730. doi:10.1016/S00109452(08)70775-5 Riestra, A. R., & Barrett, A. M. (2013). Rehabilitation of spatial neglect. Neurological Rehabilitation, 110, 347–355. doi:10.1016/B978-0-444-52901-5.00029-0 Rohrer, J. D., Caso, F., Mahoney, C., Henry, M., Rosen, H. J., Rabinovici, G., & Gorno-Tempini, M. L. (2013). Patterns of longitudinal brain atrophy in the logopenic variant of primary progressive aphasia. Brain and Language, 127, 121–126. doi:10.1016/j.bandl.2012.12.008 Silveri, M. C., Ciccarelli, N., & Cappa, A. (2011). Unilateral spatial neglect in degenerative brain pathology. Neuropsychology, 25, 554–566. doi:10.1037/a0023957 Suchan, J., & Karnath, H.-O. (2011, October). Spatial orienting by left hemisphere language areas: A relict from the past? Brain, 134, 3059–3070. doi:10.1093/brain/awr120
Teichmann, M., Kas, A., Boutet, C., Ferrieux, S., Nogues, M., Samri, D., & Migliaccio, R. (2013). Deciphering logopenic primary progressive aphasia: A clinical, imaging and biomarker investigation. Brain, 136, 3474–3488. doi:10.1093/brain/awt266 Urbanski, M., Thiebaut de Schotten, M. Rodrigo, S., Oppenheim, C., Touzé, E., Méder, J. F., & Bartolomeo, P. (2011, February). DTI-MR tractography of white matter damage in stroke patients with neglect. Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale, 208, 491–505. doi:10.1007/s00221-010-2496-8 Vallar, G., & Perani, D. (1986). The anatomy of unilateral neglect after right-hemisphere stroke lesions. A clinical/CT-scan correlation study in man. Neuropsychologia, 24, 609–622. doi:10.1016/0028-3932(86)90001-1 Verdon, V., Schwartz, S., Lovblad, K.-O., Hauert, C.-A., & Vuilleumier, P. (2010). Neuroanatomy of hemispatial neglect and its functional components: A study using voxel-based lesion-symptom mapping. Brain, 133, 880–894. doi:10.1093/brain/awp305 Watson, R. T., & Heilman, K. M. (1979, May). Thalamic Neglect. Neurology, 29, 690-690. doi:10.1212/WNL.29.5.690 Watson, R. T., Heilman, K. M., Miller, B. D., & King, F. A. (1974, March). Neglect after mesencephalic reticular formation lesions. Neurology, 24, 294–294. doi:10.1212/WNL.24.3.294 Weintraub, S., Daffner, K. R., Ahern, G. L., Price, B. H., & Mesulam, M. M. (1996, March). Right sided hemispatial neglect and bilateral cerebral lesions. Journal of Neurology, Neurosurgery & Psychiatry, 60, 342–344. doi:10.1136/jnnp.60.3.342 Wicklund, M. R., Duffy, J. R., Strand, E. A., Whitwell, J. L., Machulda, M. M., & Josephs, K. A. (2013, September). Aphasia with left occipitotemporal hypometabolism: A novel presentation of posterior cortical atrophy? Journal of Clinical Neuroscience, 20, 1237–1240. doi:10.1016/j.jocn.2013.01.002 Zilli, E. M., & Heilman, K. M. (2015). Allocentric spatial neglect with posterior cortical atrophy. Neurocase, 21, 190–197. doi:10.1080/13554794.2013.878731