National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011850
Author(s):  
Douglas I. Katz ◽  
Charles Bernick ◽  
David W. Dodick ◽  
Jesse Mez ◽  
Megan L Mariani ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Features ◽  
Military Service ◽  
Chronic Traumatic Encephalopathy ◽  
Functional Dependence ◽  
Validity Data ◽  
Clinical Disorder ◽  
Modified Delphi ◽  
Delphi Procedure

Objective:To develop evidence-informed, expert consensus research diagnostic criteria for Traumatic Encephalopathy Syndrome (TES), the clinical disorder associated with neuropathologically diagnosed Chronic Traumatic Encephalopathy (CTE).Methods:A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First NINDS Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Prior to consensus, panelists reviewed evidence from all published cases of CTE with neuropathological confirmation and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathological study (n = 298).Results:Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires: 1) substantial exposure to repetitive head impacts (RHI) from contact sports, military service, or other causes; 2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; 3) a progressive course; and 4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features.Conclusions:New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathological information and in vivo biomarkers become available.

Clinical Presentation of Chronic Traumatic Encephalopathy

2020 ◽  
Vol 40 (04) ◽  
pp. 370-383
Author(s):  
Megan Mariani ◽  
Michael L. Alosco ◽  
Jesse Mez ◽  
Robert A. Stern
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Features ◽  
Clinical Presentation ◽  
Chronic Traumatic Encephalopathy ◽  
Case Reports ◽  
Case Series ◽  
American Football ◽  
Next Of Kin ◽  
Motor Functioning

AbstractChronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts (RHI), such as those received in contact/collision sports, blast injury in military veterans, and domestic violence. Currently, CTE can only be diagnosed following death. Although the clinical features of former boxers have been described for almost a century, and there is increasing evidence of long-term cognitive and neuropsychiatric impairments in living former American football players, the specific clinical presentation associated with underlying CTE neuropathology remains unclear. These features include diverse and nonspecific changes in cognition, mood, behavior, and motor functioning. Currently, there are no validated and widely accepted clinical diagnostic criteria. Proposed criteria are primarily based on retrospective telephonic interviews with the next of kin of individuals who were diagnosed with CTE postmortem. Prospective studies involving individuals presumably at high risk for CTE are underway; these will hopefully clarify the clinical features and course of CTE, allow the diagnostic criteria to be refined, and lead to the development and validation of in vivo biomarkers. This article reviews what is currently known about the clinical presentation of CTE and describes the evolution of this knowledge from early case reports of “punch drunk” boxers through larger case series of neuropathologically confirmed CTE. This article concludes with a discussion of gaps in research and future directions to address these areas.

ATYPICAL ADRENAL HYPERFUNCTION: IN VIVO STUDIES AND INCUBATIONS OF ADRENAL TISSUE WITH 4-14C PROGESTERONE

1968 ◽  
Vol 58 (3_Suppl) ◽  
pp. S5-S34
Author(s):  
Joseph W. Goldzieher ◽  
Leonard R. Axelrod ◽  
Arthur S. Weissbein
Keyword(s):  
Urinary Excretion ◽  
Clinical Features ◽  
In Vivo Studies ◽  
Acth Stimulation ◽  
Adrenal Tissue ◽  
Adrenal Hyperfunction

ABSTRACT Six women with atypical forms of adrenal cortical hyperfunction were studied by means of urinary excretion of 17-ketosteroids and 17-hydroxycorticoids and their response to ACTH stimulation and corticosteroid suppression. Unusual responses were observed, particularly with respect to the independence of 17-KS and 17-OHCS excretion. The adrenals of 3 patients were anatomically normal whereas the others showed hyperplasia. Minced adrenal tissue was incubated with 4-14C progesterone and the metabolites isolated and definitively identified. The pattern of biosynthesized corticosteroids showed great variation, and in some instances clarified certain clinical features. The pattern of certain C19-metabolites could not be studied adequately because of the use of a Δ4 rather than a Δ5 substrate.

scholarly journals Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
C. Ejerskov ◽  
M. Raundahl ◽  
P. A. Gregersen ◽  
M. M. Handrup
Keyword(s):  
Cognitive Impairment ◽  
Learning Disability ◽  
Diagnostic Criteria ◽  
Clinical Features ◽  
Neurofibromatosis Type 1 ◽  
Plexiform Neurofibroma ◽  
Neurofibromatosis Type ◽  
Language Delay

Abstract Background The mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications. Method A systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed. Results We identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries. Conclusion Patients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.

scholarly journals In vivo exploration of synaptic projections in frontotemporal dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric Salmon ◽  
Mohamed Ali Bahri ◽  
Alain Plenevaux ◽  
Guillaume Becker ◽  
Alain Seret ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Input Function ◽  
Parahippocampal Gyrus ◽  
Exploratory Research ◽  
Social Brain ◽  
Synaptic Density ◽  
Clinical Disorder ◽  
Significant Difference ◽  
The Right

AbstractThe purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer’s disease (AD). Loss of synaptic projections was assessed with [18F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, [18F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in [18F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes.

scholarly journals Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan D. Cherry ◽  
Camille D. Esnault ◽  
Zachary H. Baucom ◽  
Yorghos Tripodis ◽  
Bertrand R. Huber ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Temporal Cortex ◽  
Head Impacts ◽  
Hippocampal Subfields ◽  
Mild Disease ◽  
Tau Isoforms ◽  
Ghost Tangles

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.

Diagnostic grammar and assessment: translating criteria into questions

1989 ◽  
Vol 19 (1) ◽  
pp. 57-68 ◽  
Author(s):  
Lee N. Robins
Keyword(s):  
Diagnostic Criteria ◽  
Catchment Area ◽  
Predictive Ability ◽  
Diagnostic Interview ◽  
Good Prediction ◽  
Interview Schedule ◽  
Validity Data ◽  
Validity Assessment ◽  
Standardized Interview ◽  
The Relationship

SynopsisThere has been concern about whether standardized psychiatric interviews make valid diagnoses. Agreements between the Diagnostic Interview Schedule (DIS), as an example of a standardized interview, with independent assessments by a clinician are reasonably high in most studies, but the clinical assessment is itself of uncertain validity. Using predictive ability is an alternative way of judging validity. Data are presented to show that the DIS is almost as good at prediction as a clinician's assessment, but here too there are problems. Because prediction is probabilistic (i.e. the same disorder can have multiple outcomes, and different disorders can share outcomes), it is not possible to say how good prediction has to be to demonstrate perfect validity.Across varied methods of validity assessment, some disorders are regularly found more validly diagnosed than others, suggesting that part of the source of invalidity lies in the diagnostic grammar of the systems whose criteria standardized interviews evaluate. Sources of invalidity inherent in the content and structure of a variety of diagnoses in DSM-III and its heir, DSM-III-R, are reviewed and illustrated, in part with results from the Epidemiological Catchment Area study.The relationship between diagnostic criteria and standardized interviews is symbiotic. While attempts to adhere closely to existing diagnostic criteria contribute to the diagnostic accuracy of standardized interviews, the exercise of translating official diagnostic criteria into standardized questions highlights problems in the system's diagnostic grammar, enabling standardized interviews to contribute to improvements in diagnostic nosology.

Clinical Features and Endolymphatic Hydrops in Patients With MRI Evidence of Hydrops

2018 ◽  
Vol 128 (4) ◽  
pp. 286-292 ◽  
Author(s):  
Suming Shi ◽  
Ping Guo ◽  
Wenquan Li ◽  
Wuqing Wang
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Features ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Endolymphatic Hydrops ◽  
Low Frequency ◽  
Clinical Severity ◽  
Mri Findings ◽  
Vestibular Symptoms ◽  
Magnetic Resonance Imaging Mri

Objectives: The purpose of this study was to investigate the correlation between grades of endolymphatic hydrops (ELH) and clinical characteristics and determine the detailed clinical characteristics of Ménière’s disease (MD) patients with evidence of hydrops based on magnetic resonance imaging (MRI). Methods: One hundred ninety-eight MD patients (396 ears) with MRI evidence of hydrops were included. ELH grades were evaluated using the Nakashima grading standard. Correlations between the extent of ELH and clinical features were evaluated. Detailed clinical characteristics were analyzed to assess the clinical diagnostic criteria. Results: Of 198 patients, ELH was observed in 100% of cases on the clinically affected side and 8.6% of cases on the asymptomatic side. In addition, 98.5% of ELH was classified as moderate or significant grade. Low-frequency hearing loss was significantly correlated with the extent of both vestibular and cochlear hydrops, whereas the vertigo attack frequency showed no significant correlation with ELH grades. The disease duration of MD with bilateral ELH was longer than that with unilateral ELH. The clinical characteristics were variant and did not completely fit the proposed diagnostic criteria. Conclusions: MRI findings have relevance to the clinical severity, to a certain extent, but not vestibular symptoms. The proposed diagnostic criteria based on clinical characteristics may be partially effective; analysis of the detailed clinical characteristics of MD was meaningful. Diagnosis of MD based on both MRI and clinical symptoms could facilitate an early diagnosis.

scholarly journals KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation

2010 ◽  
Vol 19 (18) ◽  
pp. 3642-3651 ◽  
Author(s):  
Maria M. Alves ◽  
Grzegorz Burzynski ◽  
Jean-Marie Delalande ◽  
Jan Osinga ◽  
Annemieke van der Goot ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Neuronal Differentiation ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Direct Interaction ◽  
Clinical Disorder ◽  
Neurite Development

Abstract Goldberg–Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo . To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.

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