Natalia García-Casares

Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study.

BACKGROUND Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question. OBJECTIVE We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects. METHODS Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group. RESULTS Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions. CONCLUSION In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

Cognitive Dysfunctions in Middle-Aged Type 2 Diabetic Patients and Neuroimaging Correlations: A Cross-Sectional Study

BACKGROUND/OBJECTIVE The aim was to assess the neuropsychological performance of a group of middle-aged patients with well-controlled type 2 diabetes mellitus (T2DM) and to examine whether the neuropsychological deficits correlate with structural and functional brain alterations. METHODS We compared 25 subjects with T2DM aged 45-65 years with 25 control participants matched for age, gender, and educational level. The neuropsychological battery was designed to examine executive functions, attention, information processing speed, and verbal memory. Severity of depression was assessed using the Hamilton Depression Rating Scale and cardiovascular risk factors were assessed using the Framingham Cardiovascular Risk Profile Score. The presence of at least one APOEε4 allele was determined. Reduced gray matter density was analyzed using voxel-based morphometry and brain glucose metabolic changes were assessed by 18FDG-PET. RESULTS T2DM subjects had significantly lower scores than subjects without T2DM in the Trail-making Test B (p < 0.004), Color-Word Stroop test (p < 0.005), Semantic Fluency (p < 0.006), Digit-Symbol modalities test (p < 0.02), Text Recall from the Wechsler Memory Scale (p < 0.0001), Rey-Osterrieth Complex Figure-copy (p < 0.004), and delayed reproduction (p < 0.03). Worse executive functions and memory functioning correlated predominantly with less gray matter density and reduced glucose metabolism in the orbital and prefrontal cortex, temporal (middle gyrus, parahippocampus and uncus), and cerebellum regions (p < 0.001). CONCLUSIONS T2DM subjects presented cognitive dysfunctions compared with controls. Clinical-neuroimaging correlations corresponded to brain changes (reduced gray matter density and glucose metabolism) mainly in fronto-temporal areas.

Foreign accent syndrome: a multimodal evaluation in the search of neuroscience-driven treatments.

Foreign accent syndrome (FAS) is a rare condition which is placed in the mildest end of the spectrum of speech disorders. The impairment, not severe enough to elicit phonological errors, is associated with various alterations in the fine execution of speech sounds which cause the impression of foreignness. There is a growing interest in the study of linguistic and paralinguistic components, psychosocial aftermaths, and neural basis of FAS, but there are not yet neuroscience-driven treatments for this condition. A multimodal evaluation was conducted in a single patient with the aim of searching for clues which may assist to design neuroscience-driven therapies. The patient was a middle-aged bilingual woman who had chronic FAS. She had segmental deficits, abnormal production of linguistic and emotional prosody, impaired verbal communication, and reduced motivation and social engagement. Magnetic resonance imaging showed bilateral small lesions mainly affecting the left deep frontal operculum and dorsal anterior insula. Diffusion tensor tractography suggested disrupted left deep frontal operculum-anterior insula connectivity. Metabolic activity measured with positron emission tomography was primarily decreased in key components of networks implicated in planning and execution of speech production, cognitive control and emotional communication (Brodmanns areas 4/6/9/10/13/25/47, basal ganglia, and anterior cerebellar vermis). Compensatory increases of metabolic activity were found in cortical areas (left anterior cingulate gyrus, left superior temporal gyrus and right prefrontal cortex) associated with feedback and focal attention processes critical for monitoring and adjustment of verbal utterances. Moreover, bilateral structural and functional abnormalities probably interrupted the trajectory of the lateral and medial cholinergic pathways causing region-specific hypoactivity. The results from this study provide targets for further investigation and some clues to design therapeutic interventions.

Dissociated repetition deficits in aphasia can reflect flexible interactions between left dorsal and ventral streams and gender-dimorphic architecture of the right dorsal stream

Assessment of brain-damaged subjects presenting with dissociated repetition deficits after selective injury to either the left dorsal or ventral auditory pathways can provide further insight on their respective roles in verbal repetition. We evaluated repetition performance and its neural correlates using multimodal imaging (anatomical MRI, DTI, fMRI, and18FDG-PET) in a female patient with transcortical motor aphasia (TCMA) and in a male patient with conduction aphasia (CA) who had small contiguous but non-overlapping left perisylvian infarctions. Repetition in the TCMA patient was fully preserved except for a mild impairment in nonwords and digits, whereas the CA patient had impaired repetition of nonwords, digits and word triplet lists. Sentence repetition was impaired, but he repeated novel sentences significantly better than clichés. The TCMA patient had tissue damage and reduced metabolism in the left sensorimotor cortex and insula. DTI showed damage to the left temporo-frontal and parieto-frontal segments of the arcuate fasciculus (AF) and part of the left ventral stream together with well-developed right dorsal and ventral streams, as has been reported in more than one-third of females. The CA patient had tissue damage and reduced metabolic activity in the left temporoparietal cortex with additional metabolic decrements in the left frontal lobe. DTI showed damage to the left temporo-parietal and temporo-frontal segments of the AF, but the ventral stream was spared. The direct segment of the AF in the right hemisphere was also absent with only vestigial remains of the other dorsal subcomponents present, as is often found in males. fMRI during word and nonword repetition revealed bilateral perisylvian activation in the TCMA patient suggesting recruitment of spared segments of the left dorsal stream and right dorsal stream with propagation of signals to temporal lobe structures suggesting a compensatory reallocation of resources via the ventral streams. The CA patient showed a greater activation of these cortical areas than the TCMA patient, but these changes did not result in normal performance. Repetition of word triplet lists activated bilateral perisylvian cortices in both patients, but activation in the CA patient with very poor performance was restricted to small frontal and posterior temporal foci bilaterally. These findings suggest that dissociated repetition deficits in our cases are probably reliant on flexible interactions between left dorsal stream (spared segments, short tracts remains) and left ventral stream and on gender-dimorphic architecture of the right dorsal stream.

Atypical conduction aphasia and the right hemisphere: Cross-hemispheric plasticity of phonology in a developmentally dyslexic and dysgraphic patient with early left frontal damage

We report the rare case of a patient, JNR, with history of mixed handedness, developmental dyslexia, dysgraphia, and attentional deficits associated with a Klippel–Trènaunay syndrome and a small subcortical frontal lesion involving the left arcuate fasciculus. In adulthood, he suffered a large right perisylvian stroke and developed atypical conduction aphasia with deficits in input and output phonological processing and poor auditory-verbal short-term memory. Lexical-semantic processing for single words was intact, but he was unable to access meaning in sentence comprehension and repetition. Reading and writing deficits worsened after the stroke and he presented a combination of developmental and acquired dysgraphia and dyslexia with mixed lexical and phonological processing deficits. This case suggest that a small lesion sustained prenatally or early in life could induce a selective rightward shift of phonology sparing the standard left hemisphere lateralisation of lexical-semantic functions.

Alzheimer’s like brain changes correlate with low adiponectin plasma levels in type 2 diabetic patients

AIM To study the association between adiponectin plasma levels, and gray matter brain volume and cerebral glucose metabolism in a group of type 2 diabetes patients. METHODS We studied 25 type 2 diabetes patients and 25 age- and gender-matched healthy control participants. Biochemical analysis and structural cerebral magnetic resonance imaging, including voxel-based morphometry and (18)-fluorodeoxyglucose positron emission tomography, were performed. The gray matter volumes and metabolism changes were analyzed using statistical parametric mapping (SPM8). RESULTS Lower levels of adiponectin correlated with a lower gray matter volume in temporal regions and with reduced cerebral glucose metabolism in temporal regions (p<0.001), adjusted for age, gender, education, and the presence of at least one epsilon 4 allele for the apolipoprotein E (APOEε4 genotype). CONCLUSIONS Positive correlations between adiponectin plasma levels and both gray matter volume and cerebral glucose metabolism were found, predominantly in temporal regions, as in Alzheimers disease. Adiponectin might be a biomarker for the cognitive decline associated with type 2 diabetic patients.

Restoration of conceptual knowledge in a case of semantic dementia

Patients with semantic dementia (SD) may undergo successful relearning of object names, but these gains are usually restricted to the trained exemplars, demonstrating poor generalization. We hypothesized that generalization could be improved by restoring an item’s semantic network through specific strategies that recruit the remaining personal semantic memories (conceptual enrichment therapies). We describe the case of a patient with SD who showed greater generalization of learning following a conceptual enrichment therapy than when learning items in a word-retrieval therapy. Our results suggest that enhancing an item’s semantic network connections may result in improved generalization of learning in SD. A learning mechanism in the presence of compromised hippocampi is also discussed.

Post-stroke Aphasia

Aphasia is a generic term used to describe a range of impairments in language function following acquired brain damage typically involving the left hemisphere [1–3]. Aphasia may affect all modes of expressive and receptive communication including speaking, understanding, writing, reading, and gesturing [1–3]. This definition seems superficial because it merely describes the surface behavioral deficits of aphasia (e.g., word-finding difficulty and reduced fluency) and mentions nothing about the underlying source of functional impairments. Some scientists prefer to describe aphasia as a multimodal impairment of the integral constituents of language, such as phonology, syntax, morphology, and lexical semantics [4]. Aphasia should not be regarded as a domain-specific language disorder because other cognitive skills (e.g., attention, learning, and memory and executive function) essential for normal processing of language are usually impaired as well. A growing body of evidence indicates that the adequate functioning of these nonlanguage cognitive functions is crucial for the recovery of aphasia and communication deficits [5]. This would imply that formal assessment of aphasia should not be restricted to the language domain; rather it needs to be expanded to include other cognitive and behavioral domains (see later). A new conceptualization of aphasia as a “discrete acquired disorder with a variety of aetiologies but specific characteristics” has been proposed as it provides a more informative viewpoint that may be useful to enhance public awareness of this still under-recognized condition [6]. In this chapter, we present an overview of acute and chronic post-stroke aphasia (PSA) covering epidemiology, pathophysiology, diagnosis, and treatment.

Ureteric myxoedema. A new location in Graves' disease

Graves’ disease is an autoimmune disorder of the thyroid gland that can be accompanied by extra-thyroidal manifestations. These include ophthalmopathy, present in 30% of patients, and, less commonly, dermopathy (pretibial myxoedema) in 1–4% of patients. Much less frequent (<1%) is acropachy (osteoarthropathy) with finger clubbing. This triad constitutes the exophthalmos, pretibial myxoedema and osteoarthropathy (EMO) syndrome. We present a patient with myxoedema in the ureter, which has not been described previously. The patient was a 36-year-old woman whose brother had type 1 diabetes and whose mother had type 2 diabetes. She was diagnosed with Graves’ disease at the age of 24 years, at week 28 of a twin pregnancy with foetal tachycardia. Her blood test showed: TSH <0 1 mU/l [reference range (RR) 0 3–5]; FT4 80 5 pM (RR 10–21); FT3 19 2 pM (RR 3–5); and TSH receptor Ab 76 IU/l (RR <2). She was treated with high-dose propylthiouracil, and a and b blockers for hypertension. Following an induced birth, the twins weighed 2 0 and 1 7 kg, and both had neonatal hyperthyroidism, requiring treatment for 5 and 8 months, respectively, until thyroid function was normalized. They are currently euthyroid. The patient’s condition was difficult to control, requiring high doses of antithyroid drugs (60 mg of carbimazole), but her TSH remained at 0 1 and her TSH receptor Ab was 50–70 U/ml (normal value <2). One year later, she received a therapeutic dose of I-131 (15 mCi), but still required subsequent subtotal thyroidectomy. The pathological report was diffuse hyperplasia. Her postthyroidectomy hypothyroidism is currently well controlled with 200 lg/d of L-thyroxine. From the onset of the disease, she had bilateral exophthalmos (grade 4 in the ATA classification) with diplopia and divergent strabismus. The exophthalmos and strabismus were corrected with surgery several years later. Soon after disease onset, she developed erythematous nodules in the pretibial regions, and biopsy of one such area showed a myxoedematous lesion, with abundant interstitial myxoid material among collagen bundles, more abundant in the middle and deep dermis. The dermal collagen bundles appeared to be separated by the presence of abundant, slightly basophilic, granulating material. The number of fibroblasts in the myxoid stroma was normal, although a few were star shaped. There was no inflammatory infiltrate, and the epidermis was normal. Histochemically, the myxoid material stained positive for colloidal iron and Alcian blue/PAS. Staining for IgG4 was also positive. The lesions were treated with steroids in occlusive dressings but failed to improve. The pretibial myxoedematous areas progressively worsened and enlarged, developing into a bilateral elephantiasic shape. An octreotide 111 scan was negative, despite which treatment was started with Octreotide-LAR 20 mg each 4 weeks, showing initial, short-lived improvement. She was then treated with soluble intralesional octreotide (200 mcg) for

High risk of subclinical atherosclerosis in COPD exacerbator phenotype

It is not known whether COPD exacerbations contribute to an increased vascular risk already associated with the disease. For this reason, we prospectively evaluated 127 patients referred for a monographic COPD consultation. We classify as exacerbators those who had experienced two or more moderate exacerbations in the previous year, or who had had a hospital admission. All underwent a blood analysis, respiratory function tests, global cardiovascular and coronary risk estimates (with four of the most frequently used scores, and the Chronic Obstructive Pulmonary Disease Coronaropathy Risk (COPDCoRi) score, respectively); and an EcoDoppler to measure carotid intima-media thickness and the ankle-brachial index. Finally, we included 50 patients with exacerbator phenotypes and 57 with non-exacerbator phenotypes, ranging from 63 ± 7 years old, 74% of whom were male. The exacerbator phenotype increased the risk of carotid intima-media thickness above the 75th percentile range by a factor of almost three, independently of the severity of COPD and global cardiovascular risk. The association between the exacerbator phenotype and high c-IMT was more evident in patients under 65. In conclusion, the presence of subclinical atherosclerosis is independently associated with the exacerbator phenotype, with more pronounced differences in younger patient; which suggests that we should intensify control of vascular risk factors in these groups of patients.