Clinical and structural disconnectome evaluation in a case of optic aphasia.

Optic Aphasia (OA) and Associative Visual Agnosia (AVA) are neuropsychological disorders characterized by impaired naming on visual presentation. From a cognitive point of view, while stimulus identification is largely unimpaired in OA (where access to semantic knowledge is still possible), in AVA it is not. OA has been linked with right hemianopia and disconnection of the occipital right-hemisphere (RH) visual processing from the left hemisphere (LH) language areas.In this paper, we describe the case of AA, an 81-year-old housewife suffering from a deficit in naming visually presented stimuli after left occipital lesion and damage to the interhemispheric splenial pathway. AA has been tested through a set of tasks assessing different levels of visual object processing. We discuss behavioral performance as well as the pattern of lesion and disconnection in relation to a neurocognitive model adapted from Luzzatti and colleagues (1998). Despite the complexity of the neuropsychological picture, behavioral data suggest that semantic access from visual input is possible, while a lesion-based structural disconnectome investigation demonstrated the splenial involvement.Altogether, neuropsychological and neuroanatomical findings support the assumption of visuo-verbal callosal disconnection compatible with a diagnosis of OA.

Left and right corticobasal syndrome: comparison of cognitive profiles between metabolic imaging - matched groups.

BACKGROUND: Corticobasal syndrome (CBS) is typically asymmetric. Case reports suggest that left-hemisphere CBS (lhCBS) is associated with major language impairment, and right-hemisphere CBS (rhCBS) is associated with major visuospatial deficits, but no group study has ever verified these observations. In our study, we enrolled 49 patients with CBS, classified them as lhCBS or rhCBS based on asymmetry of hypometabolism on brain FDG-PET and compared their cognitive and behavioural profiles. METHODS: We defined asymmetry of hypometabolism upon visual inspection of qualitative PET images and confirmed it through paired comparison of left- and right-hemisphere FDG uptake values. The two groups were also matched for severity of hypometabolism within the more affected and more preserved hemispheres, to unravel differences in the cognitive profiles ascribable specifically to each hemisphere's functional specializations. All patients were assessed for memory, language, executive and visuospatial deficits, apraxia, neglect, dyscalculia, agraphia and behavioural disturbances. RESULTS: LhCBS (n. 26) and rhCBS (n. 23) patients did not differ for demographics, disease duration and severity of global cognitive impairment. The two cognitive profiles were largely overlapping, with two exceptions: Digit span forward was poorer in lhCBS, and visual neglect was more frequent in rhCBS. CONCLUSIONS: After balancing out patients for hemispheric hypometabolism, we did not confirm worse language or visuospatial deficits in, respectively, lhCBS and rhCBS. However, verbal short-term memory was more impaired in lhCBS, and spatial attention was more impaired in rhCBS. Both of these functions reflect the functional specialization of the left and right fronto-parietal pathways, i.e. of the main loci of neurodegeneration in CBS.

A cognitive marker for Alzheimer disease pathology in primary progressive aphasia? A validation study in the clinical setting.

We validated in the clinical setting a putative clinical marker for a biological diagnosis of primary progressive aphasia (PPA) due to amyloid previously identified in an autopsy cohort and including impaired (score ≤4) digit span (DS) as index of phonological loop dysfunction and broadened criteria for logopenic PPA. In 29 PPA patients with an amyloid-positive (A+) biomarker and 28 PPA patients with an amyloid-negative (A-) biomarker, Receiver Operating Characteristics (ROC) curve analysis showed moderate specificity (71%) but insufficient sensitivity (41%) for the proposed marker. Specificity was particularly poor (58%) for the discrimination between A+ PPA and the A- subgroup with nonfluent PPA. DS may be compromised in both logopenic and nonfluent PPA, whose loci of neurodegeneration lie at the 2 ends of the left fronto-parieto-temporal system that underpins phonology. An Statistical Parametric Mapping (SPM) correlation analysis between DS score and metabolism on brain 18-fluoro-deoxy-glucose positron emission tomography also showed a major contribution of the left frontal cortex to impaired span.

Depressive Pseudodementia with Reversible AD-like Brain Hypometabolism: A Case Report and a Review of the Literature.

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer's disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man with DP (MMSE 16/30), whose FDG-PET visual rating and semiquantitative analysis closely mimicked the typical AD pattern, showing severe hypometabolism in bilateral precuneus, parietal and temporal lobes, and sparing frontal areas, suggesting the diagnosis of moderate AD. Shortly after starting antidepressant polytherapy, he underwent formal NPS testing, which revealed moderate impairment of episodic memory and mild impairment on executive and visuospatial tests, judged consistent with neurodegenerative dementia and concomitant depression. Over the following two years, he improved dramatically: repeated NPS assessment did not show significant deficits, and FDG-PET showed restoration of cerebral metabolism. The confirmation of PET findings via semiquantitative analysis, and their reversion to normality with antidepressant treatment, proved the non-neurodegenerative origin of the initial AD-like FDG-PET abnormalities. We review similar cases and provide a comprehensive analysis of their implications, concluding that reversible FDG-PET widespread hypometabolism might represent a biomarker of pseudodementia. Therefore, we suggest caution when interpreting FDG-PET scans of depressed patients with cognitive impairment.

Reduced phonemic fluency in progressive supranuclear palsy is due to dysfunction of dominant BA6.

Background: Reduced phonemic fluency is extremely frequent in progressive supranuclear palsy (PSP), but its neural correlate is yet to be defined. Objective: We explored the hypothesis that poor fluency in PSP might be due to neurodegeneration within a dominant frontal circuit known to be involved in speech fluency, including the opercular area, the superior frontal cortex (BA6), and the frontal aslant tract connecting these two regions. Methods: We correlated performance on a letter fluency task (F, A, and S, 60 s for each letter) with brain metabolism as measured with Fluoro-deoxy-glucose Positron Emission Tomography, using Statistical Parametric Mapping, in 31 patients with PSP. Results: Reduced letter fluency was associated with significant hypometabolism at the level of left BA6. Conclusion: Our finding is the first evidence that in PSP, as in other neurogical disorders, poor self-initiated, effortful verbal retrieval appears to be linked to dysfunction of the dominant opercular-aslant-BA6 circuit.

Clinical and metabolic imaging features of late-onset and early-onset posterior cortical atrophy.

BACKGROUND AND PURPOSE: Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and 18 fluoro-deoxy-glucose positron emission tomography (FDG-PET) features of LO and EO posterior cortical atrophy (LO_PCA, EO_PCA), the visual variant of Alzheimer's disease (AD), were compared. LO_PCA patients were also compared with a group of patients with LO typical AD (tAD). METHODS: Thirty-seven LO_PCA patients (onset age ≥ 65 years), 29 EO_PCA patients and 40 tAD patients who all underwent a standard neuropsychological battery were recruited; PCA patients were also assessed for the presence of posterior signs and symptoms. Brain FDG-PET was available in 32 LO_PCA cases, 23 EO_PCA cases and all tAD cases, and their scans were compared with scans from 30 healthy elderly controls. Within the entire PCA sample FDG uptake was also correlated with age at onset as a continuous variable. RESULTS: The main difference between the two PCA groups was a higher prevalence of Bálint-Holmes symptoms in EO cases, which was associated with the presence of severe bilateral occipito-temporo-parietal hypometabolism, whilst LO_PCA patients showed reduction of FDG uptake mainly in the right posterior regions. The latter group also showed mesial temporal hypometabolism, similarly to the tAD group, although with a right rather than left lateralization. Correlation analysis confirmed the association between older age and decreased limbic metabolism and between younger age and decreased left parietal metabolism. CONCLUSIONS: The major involvement of the temporal cortex in LO cases and of the parietal cortex in EO cases reported previously within the AD spectrum holds true also for the visual variant of AD.

Temporal lobe dysfunction in late-onset epilepsy of unknown origin.

OBJECTIVE: Epilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU. METHODS: We selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment. RESULTS: Twenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%). SIGNIFICANCE: Late-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.

Can the right hemisphere read? A behavioral and disconnectome study on implicit reading in a patient with pure alexia.

Patients with pure alexia have major difficulties in reading aloud. However, they often perform above chance level in reading tasks that do not require overt articulation of the target word - like lexical decision or semantic judgment - a phenomenon usually known as "implicit reading." There is no agreement in the literature on whether implicit reading should be attributed to relative sparing of some left hemisphere (LH) reading centers or rather to signs of compensatory endeavors by the right hemisphere (RH). We report the case of an 81-year-old patient (AA) with pure alexia due to a lesion involving the left occipital lobe and the temporal infero-mesial areas, as well as the posterior callosal pathways. Although AA's reading was severely impaired and proceeded letter by letter, she showed an above-chance-level performance for frequent concrete words in a tachistoscopic lexical decision task. A structural disconnectome analysis revealed that AA's lesion not only affected the left occipital cortex and the splenium: it also disconnected white-matter tracts meant to connect the visual word-form system to decision-related frontal areas within the LH. We suggest that the RH, rather than the LH, may be responsible for patient AA's implicit reading.