Extended FNAME performance is preserved in subjective cognitive decline but highly affected in amnestic mild cognitive impairment.

OBJECTIVE: The cognitive characterization of Alzheimer's disease risk states, such as amnestic mild cognitive impairment (aMCI) and subjective cognitive decline (SCD), is fundamental for timely diagnosis and interventions. The Face Name Associative Memory Exam (FNAME) is sensitive to early Alzheimer's disease brain changes, and an extended version captures a fuller range of associative memory abilities. We aimed to assess group effects in the extended FNAME in older adults with SCD, aMCI, and older adult controls (CON). METHOD: Two concurrently created versions of the extended FNAME were used to test three groups of older adults (CON = 35, SCD = 37, aMCI = 31) at two sites (Mexico = 59, Netherlands = 44). Extended FNAME memory abilities were analyzed in five analyses of variance. Group and site were considered as independent variables. For the recall ability, subtest levels were entered as a within-subject variable. The remaining abilities (Face Recognition, Name Recognition, Spontaneous Name Recall, and Face-Name Matching) were analyzed in independent models. RESULTS: In all models, the main effect for group was significant with large effect sizes, driven by a worse performance of aMCI participants. No significant differences were found between SCD and CON. The main effect for site was only significant in Face Recognition. CONCLUSIONS: The worse performance of aMCI in the extended FNAME implies an impairment in associative memory abilities beyond recall. The similar performance of CON and SCD might be explained by the recruitment of SCD participants that did not spontaneously seek help for memory decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparative Efficacy of Botulinum Toxin in Salivary Glands vs. Oromotor Therapy in the Management of Sialorrhea in Cerebral Palsy Impact on Sleep Quality.

Aims: The aim of this study was to compare the effects of intraglandular abobotuliniumtoxinA application and oromotor therapy in the management of sialorrhea in patients with cerebral palsy and its effect on sleep quality. Methods: A comparative study (n = 134), mean age 7.1 years (± 3.9 years) was performed in pediatric patients, between the efficacy of abobotuliniumtoxinA in salivary glands and oromotor therapy (JT), with a control group receiving exclusive oromotor therapy (EOMT). Demographic variables, as well as Gross Motor Function Classification System (GMFCS), Drooling Severity and Frequency Scale (DSFS), Sleep Disturbance Scale for Children (SDSC) and Eating and Drinking Ability Classification System (EDACS) were analyzed in 134 patients considering two measurements 6 months apart. Statistical analysis was developed between both groups. Results: The greatest improvement in safety and efficacy of swallowing were those in the JT group with initial levels of EDACS IV and V. Both therapies result in favorable changes of all subscales means of SDSC, with joint therapy showing the greater benefit (p = 0.003) over EOMT (p = 0.06), especially for Sleep Breathing Disorders and Disorders of initiating and maintaining sleep (p < 0.01 vs. p = 0.07). No major adverse effects were found, only those expected from the application of the toxin, such as pain, mild, and transient local inflammation. Interpretation: A correlation between frequency and intensity of sialorrhea, with the frequency of sleep disorders and dysphagia was found. Conventional EOMT proved to be useful, improving the safety and efficacy of swallowing, sialorrhea and sleep disorder, however it can be enhanced with the application of abobotuliniumtoxinA.

The first otologic surgery in a skull from El Pendón site (Reinoso, Northern Spain).

Archaeological research in the Dolmen of El Pendón (Reinoso, Burgos, Spain) has brought to light the complex biography of a megalithic monument used throughout the 4th millennium cal. BC. The ossuary of this burial holds the bones of nearly a hundred individuals who suffered from diverse pathologies and injuries. This study presents the discovery of a skull with two bilateral perforations on both mastoid bones. These evidences point to a mastoidectomy, a surgical procedure possibly performed to relieve the pain this prehistoric individual may have suffered as a result of otitis media and mastoiditis. The hypothesis of surgical intervention is also supported by the presence of cut marks at the anterior edge of the trepanation made in the left ear. Furthermore, the results of this paper demonstrate the survival of the individual to both interventions. Given the chronology of this dolmen, this find would be the earliest surgical ear intervention in the history of mankind.

Anosognosia in Amnestic Mild Cognitive Impairment Is Related to Diminished Hippocampal Volume Comparable to Alzheimer's Disease Dementia: Preliminary MRI Findings.

Although the presence of anosognosia in amnestic mild cognitive impairment (aMCI) may be predictive of conversion to Alzheimer's disease (AD), little is known about its neural correlates in AD and aMCI. Four different groups were compared using volumetric and diffusion magnetic resonance imaging metrics in regions of interest (hippocampus and cingulum cortex gray matter, cingulum bundle white matter): aMCI subjects with anosognosia (n = 6), aMCI subjects without anosognosia (n = 12), AD subjects with anosognosia (n = 6), and AD subjects without anosognosia (n = 9). aMCI subjects with anosognosia displayed a significantly lower gray matter density (GMD) in the bilateral hippocampus than aMCI subjects without anosognosia, which was accounted for by bilateral hippocampal differences. Furthermore, we identified that the mean hippocampal gray matter density of aMCI subjects with anosognosia was not statistically different than that of AD subjects. The groups of aMCI and AD subjects with anosognosia also displayed a lower GMD in the bilateral cingulum cortex compared to subjects without anosognosia, but these differences were not statistically significant. No statistically significant differences were found in the fractional anisotropy or mean diffusivity of the hippocampus or cingulum between subjects with and without anosognosia in aMCI or AD groups. While these findings are derived from a small population of subjects and are in need of replication, they suggest that anosognosia in aMCI might be a useful clinical marker to suspect brain changes associated with AD neuropathology.

Worse associative memory recall in healthy older adults compared to young ones, a face-name study in Spain and Mexico.

INTRODUCTION: The Face Name Associative Memory Exam (FNAME) is sensitive to associative memory changes early in the Alzheimer's disease spectrum, but little is known about how healthy aging affects FNAME performance. We aimed to assess aging effects on an extended version of the test, which captures further associative memory abilities beyond the recall and recognition domains measured in the original version. METHOD: We adapted FNAME versions in Spain and Mexico, adding new subtests (Spontaneous Name Recall, Face-Name Matching). We compared the performance of 21 young adults (YA) and 27 older adults (OA) in Spain, and 34 YA and 36 OA in Mexico. Recall was analyzed using a mixed-model ANOVA including subtest scores as dependent variables, age group as a fixed-factor independent variable, and recall subtest as a three-level repeated-measure independent variable. The rest of the associative memory domains were analyzed through t-tests comparing the performance of YA and OA. RESULTS: In Spain, we found significant effects for age group and recall subtest, with large effect sizes. The recognition subtests (Face Recognition, Name Recognition) displayed ceiling effects in both groups. The new subtests displayed medium-to-large effect sizes when comparing age groups. In Mexico, these results were replicated, additionally controlling for education. In both studies, recall performance improved after repeated exposures and it was sustained after 30 minutes in YA and OA. CONCLUSIONS: We document, in two different countries, a clear aging pattern on the extended FNAME: regardless of education, OA remember fewer stimuli than YA through recall subtests. The new subtests provide evidence on associative memory changes in aging beyond recall.

Autonomic Dysfunction in α-Synucleinopathies.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by abnormal accumulation of insoluble α-synuclein in neurons and glial cells, comprising Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although varying in prevalence, symptom patterns, and severity among disorders, all α-synucleinopathies have in common autonomic nervous system dysfunctions, which reduce quality of life. Frequent symptoms among α-synucleinopathies include constipation, urinary and sexual dysfunction, and cardiovascular autonomic symptoms such as orthostatic hypotension, supine hypertension, and reduced heart rate variability. Symptoms due to autonomic dysfunction can appear before motor symptom onset, particularly in MSA and PD, hence, detection and quantitative analysis of these symptoms can enable early diagnosis and initiation of treatment, as well as identification of at-risk populations. While patients with PD, DLB, and MSA show both central and peripheral nervous system involvement of α-synuclein pathology, pure autonomic failure (PAF) is a condition characterized by generalized dysregulation of the autonomic nervous system with neuronal cytoplasmic α-synuclein inclusions in the peripheral autonomic small nerve fibers. Patients with PAF often present with orthostatic hypotension, reduced heart rate variability, anhydrosis, erectile dysfunction, and constipation, without motor or cognitive impairment. These patients also have an increased risk of developing an α-synucleinopathy with central involvement, such as PD, DLB, or MSA in later life, possibly indicating a pathophysiological disease continuum. Pathophysiological aspects, as well as developments in diagnosing and treating dysautonomic symptoms in patients with α-synucleinopathies are discussed in this review.

Age at surgery as a predictor of cognitive improvements in patients with drug-resistant temporal epilepsy.

Temporal lobe epilepsy (TLE) surgery is an effective procedure that can produce cognitive changes. However, the prognostic factors related with cognitive outcomes need to be better understood. The aim of the present study is to know if age at surgery is a reliable predictor of verbal memory competence and considering factors such as: hemisphere; type of surgery; pre-surgical seizure frequency; and epilepsy duration. Sixty-one typically dominant patients with drug-resistant TLE (34 with left TLE [L-TLE] and 27 with right TLE [R-TLE]) underwent a neuropsychological assessment before and a year after surgery. Results showed that R-TLE patients had better evolution in short- and long-term verbal memory and naming than L-TLE patients (for all, p >.04). L-TLE patients also more frequently showed a strong and reliable decline in these functions than R-TLE patients. No effects for gender or type of surgery were found. From a multivariate approach, patients with improvements in verbal competence underwent surgery at earlier ages and suffered epilepsy for less time (for all, p <0.4). The relevance of age at surgery was confirmed as a predictor of long-term verbal memory changes, although the frequency of partial seizures also explains, at least partially, these changes. In addition, the frequency of partial seizures explains short-term verbal memory changes. These results emphasize the importance of early intervention, independently of the resected hemisphere, in order to minimize the cognitive side-effects of epilepsy treatment, as well the need to consider cognitive functions as related processes and network dependent.

Charcot-Marie-Tooth disease: genetic and clinical spectrum in a Spanish clinical series.

OBJECTIVES: To determine the genetic distribution and the phenotypic correlation of an extensive series of patients with Charcot-Marie-Tooth disease in a geographically well-defined Mediterranean area. METHODS: A thorough genetic screening, including most of the known genes involved in this disease, was performed and analyzed in this longitudinal descriptive study. Clinical data were analyzed and compared among the genetic subgroups. RESULTS: Molecular diagnosis was accomplished in 365 of 438 patients (83.3%), with a higher success rate in demyelinating forms of the disease. The CMT1A duplication (PMP22 gene) was the most frequent genetic diagnosis (50.4%), followed by mutations in the GJB1 gene (15.3%), and in the GDAP1 gene (11.5%). Mutations in 13 other genes were identified, but were much less frequent. Sixteen novel mutations were detected and characterized phenotypically. CONCLUSIONS: The relatively high frequency of GDAP1 mutations, coupled with the scarceness of MFN2 mutations (1.1%) and the high proportion of recessive inheritance (11.6%) in this series exemplify the particularity of the genetic distribution of Charcot-Marie-Tooth disease in this region.

Mesencephalic area measured by transcranial sonography in the differential diagnosis of parkinsonism.

BACKGROUND: Transcranial B-mode sonography (TCS) has become an important tool in the differential diagnosis of parkinsonism given that current technology enables an adequate assessment of brain structures. In this study we aimed at evaluating the usefulness of midbrain area measured by TCS in the differential diagnosis between Parkinson's Disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: Patients with a diagnosis of PD or PSP according to current clinical criteria were recruited. PSP patients were classified as Richardson's syndrome and PSP-parkinsonism. TCS was performed and the mesencephalic area and third ventricle width were measured offline by an examiner blinded to clinical diagnosis. RESULTS: TCS was performed in 60 patients (75% PD, 25% PSP). Eight patients (13,3%) had inadequate acoustic window. Patients with PSP had a smaller mesencephalic area (3.58 cm(2) vs 5.28 cm(2), p < 0.001). A mesencephalic area ≥4.27 cm(2) discriminates PD from PSP with a positive predictive value 100%. Patients with PSP also had a higher third ventricle diameter (8.84 mm vs 5.11 mm, p < 0.001). Within the PSP group patients with Richardson's syndrome had a wider third ventricle than patients with PSP-Parkinsonism phenotype (9.57 mm vs 7 mm, p = 0.01), but no differences were found in the mesencephalic area between both phenotypes. CONCLUSIONS: Measurement of the mesencephalic area and the third ventricle width by TCS is a non-invasive, easily accessible technique that is useful in the differential diagnosis between PD and PSP, at least in the late stages of the disease.

Late clinical and radiological complications of stereotactical radiosurgery of arteriovenous malformations of the brain.

INTRODUCTION: Post-radiation injury of patients with brain arteriovenous malformations (AVM) include blood-brain barrier breakdown (BBBB), edema, and necrosis. Prevalence, clinical relevance, and response to treatment are poorly known. We present a series of consecutive brain AVM treated with stereotactic radiosurgery describing the appearance of radiation injury and clinical complications. METHODS: Consecutive patients with annual clinical and radiological follow-up (median length 63 months). Edema and BBBB were classified in four groups (minimal, perilesional, moderate, or severe), and noted together with necrosis. Clinical symptoms of interest were intracranial hypertension, new neurological deficits, new seizures, and brain hemorrhages. RESULTS: One hundred two cases, median age 34 years, 52% male. Median irradiated volume 3.8 cc, dose to the margin of the nidus 18.5 Gy. Nineteen patients underwent a second radiosurgery. Only 42.2% patients remained free from radiation injury. Edema was found in 43.1%, blood-brain barrier breakdown in 20.6%, necrosis in 6.9%. Major injury (moderate or severe edema, moderate or severe BBBB, or necrosis) was found in 20 of 102 patients (19.6%). AVM diameter >3 cm and second radiosurgery were independent predictors. Time to the worst imaging was 60 months. Patients with major radiation injury had a hazard ratio for appearance of focal deficits of 7.042 (p = 0.04), of intracranial hypertension 2.857 (p = 0.025), hemorrhage into occluded nidus 9.009 (p = 0.079), appearance of new seizures not significant. CONCLUSIONS: Major radiation injury is frequent and increases the risk of neurological complications. Its late appearance implies that current follow-up protocols need to be extended in time.

The study of deep brain structures by transcranial duplex sonography and imaging resonance correlation.

Transcranial duplex sonography (TCS) currently provides us with images of deep brain structures with sufficient resolution. We chose 2 sonographic quantitative parameters: the diameter of the third ventricle and a measurement not used by TCS to date, the midbrain area. Their reliability and reproducibility were assessed using magnetic resonance imaging (MRI) as the reference. A total of 99 patients free from neurodegenerative disorders were examined using TCS, and both parameters were measured by 2 independent explorers. Measurements of third-ventricle diameter by TCS showed very good correlation (r = 0.80) and agreement (ICC = 0.89) with measurements obtained by MRI. Measurements of the midbrain area by TCS also provided acceptable values with moderate correlation (r = 0.36) and agreement (ICC = 0.53). Interexplorer correlation values were good (ICC = 0.98 and 0.79 for the third ventricle and midbrain areas, respectively). Further studies will be required to determine the potential diagnostic usefulness of these parameters.

Postradiosurgery hemorrhage rates of arteriovenous malformations of the brain: influencing factors and evolution with time.

BACKGROUND AND PURPOSE: The long-term benefit of radiosurgery of brain arteriovenous malformations (AVM), especially nonhemorrhagic cases, is controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed the risk factors for bleeding based on cases followed at our site. METHODS: One hundred eight patients, age 36 ± 17 years, 56 men. The mean follow-up was 65 ± 44 months (median, 54; interquartile range, 33-94). Most AVMs were small (74.1% <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep drainage, and 39.8% presented with hemorrhage. RESULTS: The annual hemorrhage rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic presentation. Older patients, cortical or subcortical AVMs, and cases with multiple draining veins were less likely to present with bleeding. During the first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%, and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension and nidus volume were independent predictors of bleeding after treatment. Mean nidus obliteration time was 37 ± 18 months (median, 32; interquartile range, 25-40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9% for AVMs that were not closed at the end of follow-up. CONCLUSIONS: Both hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with gradual decrease in their bleeding rates over the years. Albeit small, the risk of hemorrhage persists during the entirety of follow-up, being higher for cases with hemorrhagic presentation and nonobliterated AVM.

Local stimulation of the adenosine A2B receptors induces an increased release of IL-6 in mouse striatum: an in vivo microdialysis study.

Both adenosine and interleukin-6 (IL-6) have been implicated in the pathophysiology of, e.g., epileptic seizures, traumatic brain injury, and affective disorders. Stimulation of adenosine A2B receptors on astrocytes in vitro leads to the increased synthesis and secretion of IL-6. We investigated whether or not activation of adenosine receptors evokes an increase of IL-6 release also in vivo. 5'-N-ethylcarboxamidoadenosine, a non-specific adenosine-agonist or vehicle was administered into the striatum of freely moving mice by reverse microdialysis. A statistical significant increase of the IL-6 concentration in the perfusate was detected already 60 min after 5'-N-ethylcarboxamidoadenosine administration. IL-6 increased progressively and reached a maximum after 240 min. This effect appears to be mediated through adenosine A2B receptors since it was counteracted by the specific A2B receptor antagonist MRS1706 but not by the specific A1 receptor antagonist DPCPX. We conclude that adenosine via activation of A2B receptors evokes IL-6 release also in vivo.