Formal Neuropsychological Testing Research Articles

Evidence-Based Physiatry: The Center for Disease Control Guideline on Pediatric Mild Traumatic Brain Injury and the Expanded Role of Physiatry.

A mild traumatic brain injury (mTBI) or concussion is the most commonly occurring type of traumatic brain injury in adults and children. Between 2005 and 2009, the United States Center for Disease Control estimated 2–3 million pediatric mTBI-related emergency department and primary care visits occurred. Although there are subtle variation in definitions of mTBI, a consensus has formed around defining this injury as an acute neurological disturbance manifesting with confusion and/or disorientation after a mechanical force to the head and meeting the following parameters: (1) length of loss of consciousness of less than 30 mins; (2) posttraumatic amnesia less than 24 hrs; and (3) a Glasgow Coma Scale of 13–15, 30 mins after injury or at time of presentation to medical care. Guidelines have emerged to direct treatment of specific groups that commonly sustain mTBI, such as the Consensus Statement on Concussion in Sport directed at student athletes, the Ontario Neurotrauma Foundation guidelines for those with mTBI and persistent symptoms, and Veteran’s Affairs/Department of Defense guidelines for mTBI in military service members and veterans. However, evidence based guidelines for pediatric mTBI in the United States were lacking until the most recently published Center for Disease Control Guideline on the Diagnosis and Management of mTBI among Children (https://www.cdc.gov/media/releases/2018/p0904-tbi-guidelines.html).1 GUIDELINE DEVELOPMENT AND METHODOLOGY The new Center for Disease Control guideline is a set of 19 recommendations based on a systematic review of the literature and expert consensus. Clinical questions were developed by the Pediatric Mild Traumatic Brain Injury Work Group, a panel of experts that included rehabilitation specialists and physiatrists. Guidelines were developed in three clinical areas diagnosis, prognosis, and management/treatment. A systematic review of pediatric mTBI and related topics from 1990 to 2015 was conducted using the American Academy of Neurology Guidelines. Each recommendation was based on evidence obtained in the systematic review as well as other relevant scientific information and expert opinion deemed significant by the work group. This work considered strength of evidence as well as additional factors, such as the risks and benefits of the recommendation, importance of the recommendation, feasibility, patient preference, and financial cost. WHAT ARE THE HIGHLIGHTS IN THE NEW GUIDELINES? These guidelines outline a series of practical and feasible recommendations for emergency department, primary care, and specialty providers focusing on readily available mTBI assessment tools, early identification of poor prognostic factors, and education and active rehabilitation as mainstays of treatment. A complete list of recommendations is located in the guideline supplement and patient and family resources are available online (https://www.cdc.gov/traumaticbraininjury/PediatricmTBIGuideline.html).1 In summary, the guideline recommends against the routine use of neuroimaging or serum based biomarkers for diagnosis of mTBI, except when intracranial injury is suspected. Age-appropriate symptom inventories and computer-based cognitive testing should not be used alone but in conjunction with clinical assessment. In the area of prognosis, the guidelines strongly support education of patients and families about the general course of recovery in pediatric mTBI (1–3 mos) and risk factors that are associated with prolonged recovery (premorbid conditions, injury, and noninjury-related factors). Close monitoring of individuals with multiple risk factors for prolonged symptoms and referral to specialty care within 4–6 weeks of injury if symptoms persist. The guidelines strongly support education of patients and families regarding warning signs in the acute period, the emergence of postconcussive symptoms, prevention of a second, overlapping head injury, and guidance for return to school and activity. Although rest was once the mainstay of concussion treatment, the guideline emphasizes a brief period (2–3 days) of reduced activity in the acute period followed by a gradual return to school and noncontact physical activity that does not exacerbate symptoms. The guideline supports the use of individualized return to school plans based on symptom severity and highlights the importance of a collaborative effort in return to school recommendations. Referral specialists and formal neuropsychological testing is recommended in students struggling with return to school or with persistent cognitive symptoms, respectively. Treatment recommendations focus on multidisciplinary care and dedicated symptom-based treatments for acute and chronic headache, sleep dysfunction, and vestibular and oculomotor symptoms are provided. WHY IS THIS RELEVANT TO PHYSIATRISTS? Physiatrists are uniquely positioned to care for children with mTBI because of their role in leading multidisciplinary rehabilitation teams and their specific clinical expertise in pediatric rehabilitation, sports medicine, and traumatic brain injury. The guideline recommends referral to specialty and rehabilitation care in the early subacute period meaning that the number of children with mTBI referred to specialists, such as physiatry, will likely increase. The guideline supports a paradigm shift in the treatment of mTBI from a rest and recover model to an active rehabilitation, symptom-based approach including physical activity, cognitive activity, and specialized rehabilitation (i.e., vestibular). Such an approach is an ideal forum to leverage physiatric skills.

Language indicators of change of diagnosis in nonfluent-variant primary progressive aphasia

Language indicators of change of diagnosis in nonfluent-variant primary progressive aphasia

Near-total absence of REM sleep co-occurring with normal cognition: an update of the 1984 paper

BackgroundREM sleep (REMS) is considered vital for supporting well-being and normal cognition. However, it remains unclear if and how decreases in REMS impair cognitive abilities. Rare case studies of patients with REMS abolishment due to pontine lesions remain sporadic, and formal evaluation of cognitive status is lacking. In 1984, Lavie and colleagues described the case of Y.C. – a man with a pontine lesion and near-total absence of REMS who led a normal life. Here, we set out to re-evaluate this individual's REMS status 30 years after the original report, and formally assess his cognitive abilities. MethodsFour whole-night polysomnographic sleep recordings were conducted to evaluate sleep architecture. Sleep scoring was performed according to the American Academy of Sleep Medicine (AASM) guidelines. Cranial Computed Tomography (CT) imaging was performed, as well as formal neuropsychological testing to evaluate cognitive functions. ResultsY.C. averaged 4.5% of sleep time in REMS, corresponding to the 0.055 percentile of normal values for his age. Furthermore, residual REMS episodes were short and only occurred towards the end of the night. CT imaging revealed damage and metallic fragments in pons, cerebellum, and thalamus. Neuropsychological evaluation demonstrated average to high-average cognitive skills, normal memory, and motor difficulties including speech and left hand dyspraxia. ConclusionsTo our knowledge, this is the only case where REMS loss resulting from pontine lesion was re-evaluated after many years. We find a near-total absence of REMS with no signs of significant compensation throughout adult life, along with normal cognitive status. The results provide a unique perspective on the ongoing debate regarding the functional role of REMS in supporting cognition.

The Relationship between Cerebral White Matter Integrity and Cognitive Function in Mild Stroke with Basal Ganglia Region Infarcts

Mild stroke is a known risk factor for dementia. The relationship between cerebral white matter (WM) integrity and cognitive impairment (CI) in mild stroke patients with basal ganglia region infarcts is unknown. Total of 33 stroke patients and 19 age-matched controls underwent diffusion tensor imaging scans and a formal neuropsychological test battery. CI was defined as having a performance score 1.5 SD below the established norm. We compared the differences in Z-scores and Fraction Anisotropy (FA) values among controls, stroke with no CI (NCI) and stroke with CI groups. Multiple linear regressions were performed between FA values in affected regions and neuropsychological tests in stroke patients. The majority of stroke patients were in their 50s (56.90 ± 9.23 years). CI patients exhibited a significantly decreased Z score in visual delayed memory and remarkably decreased FA values in the right external capsule and right fornix (FWE-corrected) compared with NCI patients and controls. In stroke patients, the FA value in the right fornix was positively correlated with delayed visual memory. Mild stroke with basal ganglia region infarcts may be related to widespread abnormality of WM integrity. The lower WM integrity in the right fornix may be a marker of impaired delayed visual memory.

Surgical management of colloid cysts in children: experience at a tertiary care center.

Colloid cysts are uncommon lesions in the pediatric age group, which most commonly occur in the fourth through fifth decades. The authors hereby report a series of 36 patients with colloid cysts in the pediatric age group. A retrospective chart review was conducted on all patients with colloid cyst who underwent surgery in our institute between November 2003 and December 2016 (13years). Patients above the age of 18 were excluded from the study. They were analyzed based on clinical presentation, radiological findings, surgical approaches, and outcome. There were 36 pediatric patients selected for the study. Age ranged from 8 to 18years. The male-to-female ratio was 3.5:1. Headache and vomiting were the most common symptoms, and papilledema is the most common clinical sign. The mean duration of symptoms was 9months (range 1day to 5years), but 27 (75%) of the children had precipitous symptoms just before presentation. Preoperative CT showed a hyperdense non-enhancing lesion in the majority of cases. Endoscopic excision was done in 13; 5 patients underwent transcortical transventricular excision, while transcallosal approach was opted for in 17 patients. In one patient, the colloid cyst could not be removed endoscopically and had to be converted to transcortical transventricular approach. Postoperatively, five patients developed CSF leak. They were successfully managed conservatively. One patient had operative site extra dural hematoma and underwent re-exploration, and two patients had transient hemiparesis which improved spontaneously. The median follow-up period was 9months in the 30 available patients. Though no formal neuropsychological testing was done at follow-up, all children appeared to be doing well without memory disturbances. Pediatric colloid cysts are less common and may show rapid deterioration. Timely surgery results in a permanent cure with minimum morbidity. The results of either micro neurosurgical or endoscopic operative excision of colloid cysts in children are excellent. All children who are symptomatic with raised intracranial pressure due to a third ventricular colloid cyst should undergo definitive surgery. There were no major permanent deficits in memory or disconnection syndromes observed with the limited anterior colostomy.

Reliability and Validity of a Danish Version of the Multiple Sclerosis Neuropsychological Screening Questionnaire.

More than half of all patients with multiple sclerosis (MS) acquire cognitive impairment as part of their disease progression. Because cognitive dysfunction adds substantially to disability and coping strategies, a cost-effective screening tool is needed for cognitive impairment. The Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) has previously shown good validity in American, Argentinean, and Dutch MS cohorts. We sought to test reliability and validity of a Danish translation of the MSNQ compared with formal neuropsychological testing, and measures of depression and disability, and to compare self-reported cognition with Symbol Digit Modalities Test (SDMT) results. Of 126 patients with MS and their informants tested with the MSNQ, 77 also underwent formal neuropsychological testing. All patients were tested with the SDMT and assessed clinically using the Expanded Disability Status Scale and MS Impairment Scale. The test-retest reliability of the MSNQ-P was significant (R2 = 0.79, P < .0001). R2 of informants (MSNQ-I) and patients (MSNQ-P) was much lower (R2 = 0.22, P < .0001). Compared with formal neuropsychological testing, the MSNQ-P and MSNQ-I performed poorly, with no correlation to individual neuropsychological tests, combined neuropsychological tests, or disability scores (Expanded Disability Status Scale and MS Impairment Scale). Depression/anxiety (Beck Depression Inventory) showed a weak linear relationship (R2 = 0.25, P < .0001), suggesting that the MSNQ-P measures these items more than the cognitive abilities of the patients. This study does not support use of the MSNQ as a sensitive or valid screening tool for cognitive impairment in Danish patients with MS.

Deep brain and cortical stimulation for epilepsy.

Deep brain and cortical stimulation for epilepsy.

Can patients and their caregivers boost identification of HIV Associated Neurocognitive Disorder (HAND)?

Objective: To ascertain whether people living with HIV and their caregivers using a self reflective tool could identify S&amp;S of HAND. Design: This study was a nurse led prospective observational multi-site study using a quantitative design. Setting: Participants were recruited from three sites in Sydney, New South Wales (NSW), Australia: an inner metropolitan HIV clinic, an inner metropolitan sexual health clinic and a suburban hospital HIV clinic. Subjects: 121 patients and 44 caregivers who attended ambulatory clinics providing HIV care. Main Outcome Measures: Observing usual standard of care to follow patients who had formal neuropsychological testing and diagnosis of HAND. Results: Sixty one percent of participants and 57% of caregivers identified more than four symptoms. Sixteen had neuropsychological exams; five were diagnosed with HAND. After changes to their medication regime all of those five showed an improvement in cognition. Of the remaining 11, four results were inconclusive, with some deficits noted. Conclusion: Patients and caregivers stated the booklet helped them to reflect on behavior changes which they could subsequently discuss with their doctor. The booklet was considered useful to identify S&amp;S which could indicate HAND.

Outcomes after hemispherectomy in adult patients with intractable epilepsy: institutional experience and systematic review of the literature.

OBJECTIVE Hemispherectomy is a surgical technique that is established as a standard treatment in appropriately selected patients with drug-resistant epilepsy. It has proven to be successful in pediatric patients with unilateral hemispheric lesions but is underutilized in adults. This study retrospectively evaluated the clinical outcomes after hemispherectomy in adult patients with refractory epilepsy. METHODS This study examined 6 cases of hemispherectomy in adult patients at Barrow Neurological Institute. In addition, all case series of hemispherectomy in adult patients were identified through a literature review using MEDLINE and PubMed. Case series of patients older than 18 years were included; reports of patients without clear follow-up duration or method of validated seizure outcome quantification were excluded. Seizure outcome was based on the Engel classification. RESULTS A total of 90 cases of adult hemispherectomy were identified, including 6 newly added by Barrow Neurological Institute. Sixty-five patients underwent functional hemispherectomy; 25 patients had anatomical hemispherectomy. Length of follow-up ranged from 9 to 456 months. Seizure freedom was achieved in 80% of patients. The overall morbidity rate was low, with 9 patients (10%) having new or additional postoperative speech or language dysfunction, and 19 patients (21%) reporting some worsening of hemiparesis. No patients lost ambulatory or significant functional ability, and 2 patients had objective ambulatory improvement. Among the 41 patients who underwent additional formal neuropsychological testing postoperatively, overall stability or improvement was seen. CONCLUSIONS Hemispherectomy is a valuable surgical tool for properly selected adult patients with pre-existing hemiparesis and intractable epilepsy. In published cases, as well as in this series, the procedure has overall been well tolerated without significant morbidity, and the majority of patients have been rendered free of seizures.

Decline in changing Montreal Cognitive Assessment (MoCA) scores is associated with post-stroke cognitive decline determined by a formal neuropsychological evaluation.

ObjectivesWe aimed to examine changes in the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores within a one-year period after stroke/transient ischemic attack (TIA) in associating cognitive decline determined by a formal neuropsychological test battery.MethodsPatients with ischemic stroke/TIA received MoCA and MMSE at baseline within 14 days after stroke/TIA, at 3–6 months and 1-year follow-ups. The scores of MoCA and MMSE were considered to have declined if there were a reduction of ≥2 points in the respective scores measured across two time points. The decline in neuropsychological diagnosis transitional status was defined by a category transition from no cognitive impairment or any cognitive impairment to a more severe cognitive impairment or dementia.Results275 patients with a mean age of 59.8 ± 11.6 years, and education of 7.7 ± 4.3 years completed all the assessments at baseline, 3–6 months and 1-year follow-ups. A decline in MoCA scores from 3–6 months to 1 year was associated with higher risk of decline in diagnosis transitional status (odd ratio = 3.21, p = 0.004) in the same time period whereas there was no association with a decline in MMSE scores.ConclusionsThe decline in MoCA scores from 3–6 months to 1 year after stroke/TIA has three times higher risk for decline in the diagnosis transitional status. The decline of MoCA scores (reduction ≥ 2points) is associated with the decline in neuropsychological diagnosis transitional status.

Management of Post-Traumatic Stress (PTSD) Dementia and Other Neuro-Degenerative Disease with Photo-Medicine: Clinical Experience and Case Studies

Objective: Photobiomodulation (also known as Low Level Laser. LLLT or Cold Laser; Photo Medicine (PM)) has been a vital adjunct therapy in our clinical practice over 5 years, observations of improvement in cognition and personality were noted in several patients. As a result, selected patients with Alzheimer’s Disease, vascular dementia, post-traumatic brain injury and other neuro-degenerative diseases were treated at clinical practices in Buffalo, New York; Sarasota, Florida; Lafayette, Indiana; Phoenix, Az., and Baton Rouge, La. Over 60 patients were treated with an average of 4 times over an 8-day period all reported/exhibited improvement in their condition, except that two men who were in their seventies were in robust health but had no short-term memory and no improvement was observed. However, Theralase has developed a more efficacious system which will be more efficacious, due to increased power for ATP activation. Method: Over 150 patients with the above conditions were treated in various areas (depending on diagnosis) including the prefrontal cortex, temporal lobe, Hippocampus, and Circle of Willis for duration of two and one-half minutes every 48 hours for 5 - 6 treatments. We utilized the Theralase multi-probe (905 nm/660 nm) at 60 miliwatts. It utilizes 5 - 905 nm near infra-red diodes and 4 infra-red 660 laser diodes with a peak power of 50,000 milliwatts at peak and pulse duration of 200 nanoseconds [1]. The PTSD patients were evaluated utilizing the co-occurring disorders program screening and assessment form. Conclusion: Dementia patients exhibited varying degrees of improvement in cognitive function and personality, leading to improved quality of life and decreased caregiver burden. PTSD patients’ improvement was objectively measured by formal neuropsychological testing utilizing the form. All PTSD patients scored no emotional problems after 3 - 5 treatments and all experienced overall sense of well-being. One experienced return of ability to smell he had not had for 5 years. Similar results were reported in a Japanese study where 15 patients were followed for a year. This non-invasive and non-systemic modality of therapy could play a key role in treating progressive neurodegenerative conditions, improving quality of life, and reducing health care costs.

Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

ABSTRACTBackground: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

Screening for cognitive impairment with the Montreal Cognitive Assessment in Chinese patients with acute mild stroke and transient ischaemic attack: a validation study.

ObjectiveWe aimed to establish the cut-off point of the Montreal Cognitive Assessment (MoCA-Beijing) in screening for cognitive impairment (CI) within 2 weeks of mild stroke or transient ischaemic attack (TIA).MethodsA total of 80 acute mild ischaemic stroke patients and 22 TIA patients were recruited. They received the MoCA-Beijing and a formal neuropsychological test battery. CI was defined by 1.5 SD below the established norms on a formal neuropsychological test battery.ResultsMost stroke and TIA patients were in their 50s (53.95±11.43 years old), with greater than primary school level of education. The optimal cut-off point for MoCA-Beijing in discriminating patients with CI from those with no cognitive impairment (NCI) was 22/23 (sensitivity 85%, specificity 88%, positive predictive value=91%, negative predictive value=80%, classification accuracy=86%). The predominant cognitive deficits were characteristic of frontal-subcortical impairment, such as visuomotor speed (46.08%), attention/executive function (42.16%) and visuospatial ability (40.20%).ConclusionsA MoCA-Beijing cut-off score of 22/23 is optimally sensitive and specific for detecting CI after mild stroke, and TIA in the acute stroke phase, and is recommended for routine clinical practice.

The Combined Utility of a Brief Functional Measure and Performance-Based Screening Test for Case Finding of Cognitive Impairment in Primary Healthcare

BackgroundUse of a total risk score (TRS) based on vascular and sociodemographic risk factors has been recommended to identify patients at risk of cognitive impairment. Moreover, combining screening tests has been reported to improve positive predictive values (PPV) for case finding of cognitive impairment. ObjectiveWe investigated the utility of the conjunctive combination of the informant-based AD8 and the performance-based National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol for the detection of cognitive impairment, defined by a clinical dementia rating (CDR) score ≥0.5, in patients at risk of cognitive impairment (TRS ≥3). MethodsParticipants were recruited from 2 primary healthcare centers in Singapore and received the AD8, Montreal Cognitive Assessment, Mini-Mental State Examination, CDR, and a formal neuropsychological test battery. The scores for NINDS-CSN 5-minute protocol were extracted from the Montreal Cognitive Assessment items. Area under the receiver operating characteristics curve analyses were conducted to determine the discriminant indices of the screening instruments, the conjunctive combination (ie, screened positive on both tests), and the compensatory combination (ie, screened positive in either of or both tests). ResultsA total of 309 participants were recruited of whom 78.7% (n = 243) had CDR = 0 and 21.3% (n = 66) had CDR ≥0.5. The conjunctive combination of AD8 and NINDS-CSN 5-minute protocol achieved excellent PPV and acceptable sensitivity (PPV 91.7%, sensitivity 73.3%). ConclusionsThe conjunctive combination of the AD8 and NINDS-CSN 5-minute protocol is brief and accurate, and hence, suitable for case finding of cognitive impairment (CDR ≥0.5) in patients screened positive on the TRS in primary healthcare centers.

HIV-Associated Neurocognitive Disorders (HAND): The View of a Psychiatrist

HIV-associated neurocognitive disorders (HAND) are most commonly seen in the late symptomatic stage of HIV disease, i.e., “full-blown” AIDS. The Frascati Conference revision of the American Academy of Neurology criteria recognizes two clinical neurocognitive disorders: mild neurocognitive disorder (MND) and HIV-associated dementia (HAD). For a diagnosis of MND, there must be mild neurocognitive impairment in at least two domains of cognitive performance and, at most, a minor functional impairment in daily living, insufficient severity for a diagnosis of HAD, and no other known etiology for the symptoms. For a diagnosis of HAD, there must be severe cognitive impairment in two or more domains, at least a moderate level of functional status impairment due to the cognitive symptoms, a lack of clouding of consciousness (i.e., delirium), and no support for another etiology accounting for these symptoms. Cognitive deficits are expected to be established by formal neuropsychological testing. However, broad screening tests are frequently used in practice. HAD is an AIDS-defining diagnosis and may be the first symptom of infection in as many as 25% of patients. Both MND and HAD have been reported to have declined in incidence by as much as 50% since the introduction of effective antiretroviral therapy (ART). Yet, the frequency of HAND has remained similar to the eras prior to effective ART due to inclusion of the condition known as “asymptomatic neurocognitive impairment” (ANI) (or “sub-clinical” neurocognitive impairment). ANI occurs when there is significant cognitive decline in two or more domains of neuropsychological performance but no significant decline in functional status. It is estimated that ANI, as opposed to MND and HAD, has not significantly declined in prevalence in the HAART era.

Plasma Biomarkers of HIV-associated Cognitive Disease

By controlling human immunodeficiency virus (HIV) replication and allowing recovery of immune system function, combination antiretroviral therapy (cART) has revolutionised the outlook for people-living-with-HIV (PLWH) to that of a chronic but manageable medical condition. Despite this success, other medical problems, such as hypertension and cardiovascular disease, are reported to occur more frequently and at a younger age in PLWH compared to matched control populations (Schouten et al., 2014). Another medical problem with a high prevalence and high morbidity is cognitive impairment (Robertson et al., 2007). For many co-morbidities, surrogate markers aid diagnosis and assist in the clinical staging of a disease state. For cognitive impairment however, disease markers to date have either been unreliable or impractical to measure. For instance, clinical assessments such as formal neuropsychological testing are time consuming to perform and prone to many confounding issues such as illicit drug and alcohol use, the presence of depression and anxiety, and day to day variability in a patient's performance. Novel cerebral imaging techniques show promise in the diagnosis and assessment of HIV-associated cognitive impairment (Descamps et al., 2008). However, many of these novel imaging techniques are not widely available and may only be accessible as part of a research study, rather than in general clinical care. And lastly, although cerebrospinal fluid (CSF) markers, such as neurofilament light protein (NFL) concentration, show promise, collection of CSF is problematic. Lumbar puncture, whilst generally safe, is an invasive and resource expensive procedure which does not lend itself particularly well to repeated measure (Peterson et al., 2014). In this issue of EBioMedicine, Gisslen et al. (2015) report on the measurement of plasma NFL concentrations, using a new ultrasensitive single molecule assay, and its correlations with CSF NFL concentrations in several cohorts of PLWH. Groups assessed included individuals with primary HIV-infection, neuroasymptomatic PLWH not on cART with different ranges of CD4 + lymphocyte counts (above 350 cells/uL, 200–349 cells/uL, 50–199 cells/uL and below 50 cells/uL), individuals with overt HIV-associated dementia and subjects on cART with plasma HIV RNA < 50 copies/mL for greater than one year. Furthermore an HIV-uninfected control group was included in their analysis. As expected, CSF concentration of NFL was dependent on the cohorts studied with the highest concentrations observed in those with HIV-associated dementia and higher concentrations in PLWH with untreated HIV-disease and low CD4 + lymphocyte counts. Of importance, in all groups studied, a strong correlation between plasma NFL and CSF NFL was reported. The values of NFL plasma concentrations were 1–2 log10 lower than in the CSF. However, by developing and utilising this new ultrasensitive plasma NFL assay, concentrations as low as a mean of 9.3 nmol/L were measured in the HIV-uninfected control group and every subject had a detectable and quantifiable concentration. This impressive dynamic range highlights the potential sensitivity of this biomarker to detect subtle axonal injury in a variety of patient groups. The ability to utilise a sensitive plasma biomarker which closely correlates with active CNS axonal injury has several potential implications for future research. Within longitudinal cohorts, clinical observations and non-invasive neuroimaging observations could now be correlated with readily obtainable plasma biomarkers. Within interventional studies, a novel plasma biomarker which correlates with the effects of a drug or other interventions on cerebral function, could dramatically simplify the practical issues which are currently associated with the development of such therapeutics. Furthermore, this assay has the potential in clinical practice, as well as research studies, to discriminate between those with ongoing CNS injury in whom intervention may be more successful and those with quiescent disease in whom it may not. In summary, these initial results described are highly promising with further work needed to assess the utility of this marker in other cohorts of PLWH, such as those with minor cognitive complaints, and other neurodegenerative diseases.

Determining brain fitness to fight: Has the time come?

Professional boxing is associated with a risk of chronic neurological injury, with up to 20–50% of former boxers exhibiting symptoms of chronic brain injury. Chronic traumatic brain injury encompasses a spectrum of disorders that are associated with long-term consequences of brain injury and remains the most difficult safety challenge in modern-day boxing. Despite these concerns, traditional guidelines used for return to sport participation after concussion are inconsistently applied in boxing. Furthermore, few athletic commissions require either formal consultation with a neurological specialist (i.e. neurologist, neurosurgeon, or neuropsychologist) or formal neuropsychological testing prior to return to fight. In order to protect the health of boxers and maintain the long-term viability of a sport associated with exposure to repetitive head trauma, we propose a set of specific requirements for brain safety that all state athletic commissions would implement.

Development of Subjective Cognitive Decline

Subjective cognitive decline (SCD) is common in older people. It is an upsetting symptom in which seemingly healthy individuals report self-perceived decline in cognition function, usually memory, without objective evidence on formal neuropsychological tests. There is rapidly growing evidence that SCD may be an early symptomatic sign of the first effects of Alzheimer's disease (AD) pathology on cognitive functioning between complete compensation and incipient decline. In the future, performing effective treatment at this stage would likely preserve function at a high level. Thus, the valid application of SCD as an effective tool for the early detection of AD dementia would therefore be of significant benefit. Keywords: Alzheimer's disease, mild cognitive impairment, preclinical alzheimer's disease, subjective cognitive decline.

Childhood-onset lupus with clinical neurocognitive dysfunction shows lower streamline density and pairwise connectivity on diffusion tensor imaging.

The objective of this report is to use diffusion-tensor imaging (DTI) for investigating white-matter connectivity changes associated with neurocognitive dysfunction in childhood-onset lupus (cSLE-NCD) as measured by formal neuropsychological testing. DTI was performed in six individuals with (cSLE-NCD) and nine without neurocognitive dysfunction (cSLE-noNCD) as well as 14 healthy controls. Presence of neurocognitive deficits was identified by formal neuropsychological testing. The brain was divided into 116 regions, and pairwise connectivity (defined as the number of streamlines with an endpoint in each of those regions) and streamline density (defined as the number of streamlines passing through a region regardless of endpoints) were evaluated. Group comparisons were made for regional and global measures of streamline density and pairwise connectivity. A significant decrease in global streamline density was observed in the cSLE-NCD vs. control group (1189 vs. 1305 p = 0.002) and vs. cSLE-noNCD (1189 vs 1320 p = 0.001). The cSLE-noNCD and control groups had similar streamline density. A similar pattern for pairwise connectivity was observed with a significant decrease in the cSLE-NCD group (217) versus the cSLE-noNCD (236; p = 0.013) and control group (238; p = 0.004). Regional measures of pairwise connectivity displayed mixed results. The analysis of DTI in this pilot study shows cSLE-NCD is associated with global loss of streamline density and pairwise connectivity, suggesting breakdown of the structural network. These results complement previously reported functional and volumetric findings that suggest cSLE-NCD is associated with measurable changes in gray and white matter. If confirmed in larger cohorts, DTI abnormalities could be used as imaging biomarkers of cSLE-NCD.

The association between neuropsychological performance and self-reported traumatic brain injury in a sample of adult male prisoners in the UK

This study employed a correlational and group comparison design to investigate whether self-report of traumatic brain injury (TBI) in a sample of male prisoners screened using the Brain Injury Screening Index (BISI) was associated with impaired cognitive performance on standardised questionnaires and neuropsychological tests. A total of 139 male prisoners who reported having suffered a TBI in the BISI were interviewed, and completed further questionnaires and neuropsychological assessments. Their results were compared to 50 prisoners who had no reported history of TBI. The results of the screening questionnaire correlated with responses in a follow-up interview, with self-report questionnaires of neurobehavioural disorder (.31 to .50) and neuropsychological measures (−.24 to −.45). The “TBI Index”, an indicator summarising the number and severity of self-reported injuries in a single score, also correlated well with scores on formal neuropsychological tests (–.20 to –.42). Self-report of traumatic brain injury among prisoners is consistently associated with measurable neuropsychological and neurobehavioural disability. The implications of these findings for current practice in identifying and referring individuals to specialist services are considered.