[Clinical practicability of the cognitive screening battery BICAMS in patients with multiple sclerosis: results of the feasibility study in Germany]. / Klinische Umsetzbarkeit der kognitiven Screeningbatterie BICAMS bei Patienten mit Multipler Sklerose: Ergebnisse der Machbarkeitsstudie in Deutschland.

BACKGROUND: Patients with multiple sclerosis (MS) suffer from cognitive impairment in 40-70% of the cases. There is evidence that the cognitive status is predictive for working ability and early retirement. Regular assessment of cognitive functionality is therefore urgently needed. PURPOSE: The German validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was evaluated in a multicentric way with respect to its feasibility in private neurological centers across Germany. METHODS: Physician assistants were trained with respect to application and scoring of BICAMS. All scored test materials were evaluated by independent neuropsychological experts. RESULTS: A total of 1606 BICAMS datasets were collected from 65 neurological centers. Of these 1573 datasets were analyzed of which 49.7% were correctly applied and scored while mistakes in application, scoring and transformation were found in 50.3%. Interrater reliability for each subtest was found to be ICC [Formula: see text] 0.953 when datasets containing mistakes were excluded. DISCUSSION: In general, BICAMS is highly recommended to be applied in standard clinical care; however, it should be emphasized that although the interrater reliability in the final sample was high, serious mistakes were found in 50.3% of cases. From these findings we conclude that nonpsychological staff have to be even more intensively trained and supervised by experts in the application and scoring of BICAMS.

Reprint of: Mapping human brain lesions and their functional consequences.

Neuroscience has a long history of inferring brain function by examining the relationship between brain injury and subsequent behavioral impairments. The primary advantage of this method over correlative methods is that it can tell us if a certain brain region is necessary for a given cognitive function. In addition, lesion-based analyses provide unique insights into clinical deficits. In the last decade, statistical voxel-based lesion behavior mapping (VLBM) emerged as a powerful method for understanding the architecture of the human brain. This review illustrates how VLBM improves our knowledge of functional brain architecture, as well as how it is inherently limited by its mass-univariate approach. A wide array of recently developed methods appear to supplement traditional VLBM. This paper provides an overview of these new methods, including the use of specialized imaging modalities, the combination of structural imaging with normative connectome data, as well as multivariate analyses of structural imaging data. We see these new methods as complementing rather than replacing traditional VLBM, providing synergistic tools to answer related questions. Finally, we discuss the potential for these methods to become established in cognitive neuroscience and in clinical applications.

Assessment of Homocysteine as a Diagnostic and Early Prognostic Biomarker for Patients with Acute Lacunar Infarction.

BACKGROUND: Although increasing evidence has demonstrated that elevated homocysteine (Hcy) levels may be an important contributor for the development of cerebral infarction, rare studies focused on its diagnostic and early prognostic roles in acute lacunar infarction. METHODS: A total of 197 patients with acute lacunar infarction and 192 to form the control group were prospectively recruited between January 2013 and February 2017. Early neurological deterioration was defined as an increase of ≥2 points in National Institutes of Health Stroke Scale or the decrease in Barthel index (BI) score at discharge. RESULTS: Univariate and multivariate logistic regression analyses revealed that higher levels of fibrinogen and Hcy were independently clinical predictors associated with lacunar infarction. Receiver operating characteristic curves analysis demonstrated that the diagnosis value of Hcy was superior to fibrinogen, with the area under the curve of 0.881 and 0.688 respectively. Using the optimal cutoff value of 15.5 µmol/L of Hcy, a sensitivity of 65% and a specificity of 100% were achieved for predicting lacunar infarction. Hcy was only significantly related with BI reduction in the males (30.5 [15.5-65.5] vs. 18 [15-24], p = 0.034) in the univariate analysis but not in the females and the multivariate analysis. CONCLUSIONS: Serum Hcy may be an independent diagnostic and not an early prognostic biomarker for patients with acute lacunar infarction.

Mapping human brain lesions and their functional consequences.

Neuroscience has a long history of inferring brain function by examining the relationship between brain injury and subsequent behavioral impairments. The primary advantage of this method over correlative methods is that it can tell us if a certain brain region is necessary for a given cognitive function. In addition, lesion-based analyses provide unique insights into clinical deficits. In the last decade, statistical voxel-based lesion behavior mapping (VLBM) emerged as a powerful method for understanding the architecture of the human brain. This review illustrates how VLBM improves our knowledge of functional brain architecture, as well as how it is inherently limited by its mass-univariate approach. A wide array of recently developed methods appear to supplement traditional VLBM. This paper provides an overview of these new methods, including the use of specialized imaging modalities, the combination of structural imaging with normative connectome data, as well as multivariate analyses of structural imaging data. We see these new methods as complementing rather than replacing traditional VLBM, providing synergistic tools to answer related questions. Finally, we discuss the potential for these methods to become established in cognitive neuroscience and in clinical applications.

Applicability of long-term electroencephalography in pre-mortem diagnosis of Creutzfeldt-Jakob disease: A case report.

Creutzfeldt-Jakob disease accounts for more than 90% of all sporadic prion disease cases. The molecular MM2 genotype has been divided into cortical and thalamic subtypes based on structures involved and is characterized clinically by progressive dementia without ataxia or typical electroencephalography changes. Proposed diagnostic criteria for MM2 cortical type sporadic Creutzfeldt-Jakob disease include progressive dementia, cortical hyper-intensity on diffusion-weighted magnetic resonance imaging, increased cerebrospinal fluid 14-3-3 protein level, and the exclusion of other types of dementia. The presence of periodic discharges on electroencephalography in MM2 cortical type were reported in 42% of the cases. We are reporting a case of sporadic Creutzfeldt-Jakob disease cortical MM2-type presenting with rapid cognitive decline, who survived 8 months since symptom onset. Brain imaging, cerebrospinal fluid analysis, and long-term electroencephalography monitoring were obtained and diagnosis was confirmed by autopsy. Short-term electroencephalography recording, performed 5 months after symptom onset, demonstrated diffuse background slowing without epileptiform activity. Long-term video electroencephalography monitoring demonstrated generalized slowing, maximum in bilateral frontal areas, which intermittently would become rhythmic (1-2 Hz) without hemispheric predominance. If the findings do not clearly meet the proposed clinical criteria for sporadic Creutzfeldt-Jakob disease, the use of long-term electroencephalography could increase the sensitivity. We question whether the lack of the characteristic findings on electroencephalography in some cases could be due to insufficient time of recording. Application of long-term electroencephalography monitoring increases the sensitivity of electroencephalography and the certainty of pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease.

Ischemic Amnesia: Causes and Outcome.

BACKGROUND AND PURPOSE: We aimed to describe the frequency and characteristics of acute ischemic stroke and transient ischemic attacks presenting predominantly with amnesia (ischemic amnesia) and to identify clinical clues for differentiating them from transient global amnesia (TGA). METHODS: We retrospectively analyzed and described all patients presenting with diffusion-weighted imaging magnetic resonance imaging-confirmed acute ischemic stroke/transient ischemic attacks with antero- and retrograde amnesia as the main symptom over a 13.5-year period. We also compared their clinical features and stroke mechanisms with 3804 acute ischemic stroke from our ischemic stroke registry. RESULTS: Thirteen ischemic amnesia patients were identified, representing 0.2% of all patients with acute ischemic stroke/transient ischemic attack. In 69% of ischemic amnesia cases, amnesia was transient with a median duration of 5 hours. Ischemia was not considered in 39% of cases. Fifty-four percent of cases were clinically difficult to distinguish from TGA, including 15% who were indistinguishable from TGA. 1.2% of all presumed TGA patients at our center were later found to have ischemic amnesia. Amnesic strokes were more often cardioembolic, multiterritorial, and typically involved the posterior circulation and limbic system. Clinical clues were minor focal neurological signs, higher age, more risk factors, and stroke favoring circumstances. Although all patients were independent at 3 months, 31% had persistent memory problems. CONCLUSIONS: Amnesia as the main symptom of acute ischemic cerebral events is rare, mostly transient, and easily mistaken for TGA. Although clinical clues are often present, the threshold for performing diffusion-weighted imaging in acute amnesia should be low.

Aging alters the dampening of pulsatile blood flow in cerebral arteries.

Excessive pulsatile flow caused by aortic stiffness is thought to be a contributing factor for several cerebrovascular diseases. The main purpose of this study was to describe the dampening of the pulsatile flow from the proximal to the distal cerebral arteries, the effect of aging and sex, and its correlation to aortic stiffness. Forty-five healthy elderly (mean age 71 years) and 49 healthy young (mean age 25 years) were included. Phase-contrast magnetic resonance imaging was used for measuring blood flow pulsatility index and dampening factor (proximal artery pulsatility index/distal artery pulsatility index) in 21 cerebral and extra-cerebral arteries. Aortic stiffness was measured as aortic pulse wave velocity. Cerebral arterial pulsatility index increased due to aging and this was more pronounced in distal segments of cerebral arteries. There was no difference in pulsatility index between women and men. Dampening of pulsatility index was observed in all cerebral arteries in both age groups but was significantly higher in young subjects than in elderly. Pulse wave velocity was not correlated with cerebral arterial pulsatility index. The increased pulsatile flow in elderly together with reduced dampening supports the pulse wave encephalopathy theory, since it implies that a higher pulsatile flow is reaching distal arterial segments in older subjects.

Does treatment have an impact on incidence and risk factors for autism spectrum disorders in children with infantile spasms?

OBJECTIVE: Infantile spasms (IS) are a severe form of childhood epilepsy associated with autism spectrum disorders (ASD) in up to 35% of cases. The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome. METHODS: Patients with IS were randomized in a standardized diagnostic and treatment protocol. Clinical and electroencephalogram (EEG) evaluations were completed at all eight visits over 5 years, while cognitive evaluations were administered at 0, 6, 24 and 60 months, respectively. Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule-Generic (ADOS-G). RESULTS: Of the 69 patients included in the study, 25 could not be assessed due to severe delay or death. Eleven of the 42 patients screened with CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10 were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80% ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD. Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p = 0.007) and being of nonwhite origin (p = 0.009). SIGNIFICANCE: ASD was only observed in children with sympyomatic IS. Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin. Early diagnosis and treatment did not prevent ASD as an outcome of IS. However, patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome.

Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly.

Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-ß load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-ß load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, -0.08 if on the amyloid pathway and -0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories adversely and are major drivers of cognitive decline in the elderly; and (ii) cognitive reserve seems to offset the deleterious effect of both pathologies on the cognitive trajectories.

Examining language functions: a reassessment of Bastian's contribution to aphasia assessment.

Henry Charlton Bastian (1837-1915) developed his network model of language processing, modality deficits and correlated lesion localizations in the 1860s and was a leading clinical authority for over four decades. Although his ideas are little referenced today, having been overshadowed by his more eminent Queen Square colleague John Hughlings Jackson, his work on aphasia and paralysis was highly regarded by contemporaries. This paper traces Bastian's lasting but largely unattributed contribution to the development of standardized clinical assessment of language disorders. From 1867 onwards, Bastian trained generations of medical students in neurology. In his 1875 book On Paralysis there is evidence in his case descriptions that Bastian had already implemented a detailed set of procedures for examining aphasic patients. In 1886, Bastian published a 'Schema for the Examination of Aphasic and Amnesic Persons'. Bastian insisted on the utility of this battery for diagnosis, classification and lesion localization; he argued that its consistent use would allow the development of a patient corpus and the comparison of cases from other hospitals. In 1898 his Treatise on Aphasia included a list of 34 questions that were to be used to examine all patients to provide detailed and systematic evidence of spared and impaired abilities in all receptive and expressive modalities. Bastian's contribution to the development of standardized clinical aphasia assessment is reassessed through detailed analysis of his publications and those of his contemporaries as well as new material from archives and casebooks. This evidence demonstrates that his approach to diagnosis of language and other cognitive impairments has propagated through the decades. His legacy can be seen in the approach to standardized aphasia testing developed in the latter 20th century through to today.