Diagnosis of Delayed Post-Hypoxic Leukoencephalopathy (Grinker's Myelinopathy) with MRI Using Divided Subtracted Inversion Recovery (dSIR) Sequences: Time for Reappraisal of the Syndrome?

Background: Delayed Post-Hypoxic Leukoencephalopathy (DPHL), or Grinker's myelinopathy, is a syndrome in which extensive changes are seen in the white matter of the cerebral hemispheres with MRI weeks or months after a hypoxic episode. T2-weighted spin echo (T2-wSE) and/or T2-Fluid Attenuated Inversion Recovery (T2-FLAIR) images classically show diffuse hyperintensities in white matter which are thought to be near pathognomonic of the condition. The clinical features include Parkinsonism and akinetic mutism. DPHL is generally regarded as a rare condition. Methods and Results: Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T2-FLAIR images with MRI, but very extensive changes were seen in the white matter of the cerebral and cerebellar hemisphere on divided Subtraction Inversion Recovery (dSIR) images. dSIR sequences may produce ten times the contrast of conventional inversion recovery (IR) sequences from small changes in T1. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism. Conclusion: The classic features of DPHL may only represent the severe end of a spectrum of diseases in white matter following global hypoxic injury to the brain. The condition may be much more common than is generally thought but may not be recognized using conventional clinical and MRI criteria for diagnosis. Reappraisal of the syndrome of DPHL to include clinically less severe cases and to encompass recent advances in MRI is advocated.

A window into eye movement dysfunction following mTBI: A scoping review of magnetic resonance imaging and eye tracking findings.

Mild traumatic brain injury (mTBI), commonly known as concussion, is a complex neurobehavioral phenomenon affecting six in 1000 people globally each year. Symptoms last between days and years as microstructural damage to axons and neurometabolic changes result in brain network disruption. There is no clinically available objective biomarker to diagnose the severity of injury or monitor recovery. However, emerging evidence suggests eye movement dysfunction (e.g., saccades and smooth pursuits) in patients with mTBI. Patients with a higher symptom burden and prolonged recovery time following injury may show higher degrees of eye movement dysfunction. Likewise, recent advances in magnetic resonance imaging (MRI) have revealed both white matter tract damage and functional network alterations in mTBI patients, which involve areas responsible for the ocular motor control. This scoping review is presented in three sections: Section 1 explores the anatomical control of eye movements to aid the reader with interpreting the discussion in subsequent sections. Section 2 examines the relationship between abnormal MRI findings and eye tracking after mTBI based on the available evidence. Finally, Section 3 communicates gaps in our knowledge about MRI and eye tracking, which should be addressed in order to substantiate this emerging field.

Preliminary Evidence for the Clinical Utility of Tactile Somatosensory Assessments of Sport-Related mTBI.

OBJECTIVES: To evaluate the clinical utility of tactile somatosensory assessments to assist clinicians in diagnosing sport-related mild traumatic brain injury (SR-mTBI), classifying recovery trajectory based on performance at initial clinical assessment, and determining if neurophysiological recovery coincided with clinical recovery. RESEARCH DESIGN: Prospective cohort study with normative controls. METHODS: At admission (n = 79) and discharge (n = 45/79), SR-mTBI patients completed the SCAT-5 symptom scale, along with the following three components from the Cortical Metrics Brain Gauge somatosensory assessment (BG-SA): temporal order judgement (TOJ), TOJ with confounding condition (TOJc), and duration discrimination (DUR). To assist SR-mTBI diagnosis on admission, BG-SA performance was used in logistic regression to discriminate cases belonging to the SR-mTBI sample or a healthy reference sample (pooled BG-SA data for healthy participants in previous studies). Decision trees evaluated how accurately BG-SA performance classified SR-mTBI recovery trajectories. RESULTS: BG-SA TOJ, TOJc, and DUR poorly discriminated between cases belonging to the SR-mTBI sample or a healthy reference sample (0.54-0.70 AUC, 47.46-64.71 PPV, 48.48-61.11 NPV). The BG-SA evaluated did not accurately classify SR-mTBI recovery trajectories (> 14-day resolution 48%, ≤14-day resolution 54%, lost to referral/follow-up 45%). Mann-Whitney U tests revealed differences in BG-SA TOJc performance between SR-mTBI participants and the healthy reference sample at initial clinical assessment and at clinical recovery (p < 0.05). CONCLUSIONS: BG-SA TOJ, TOJc, and DUR appear to have limited clinical utility to assist clinicians with diagnosing SR-mTBI or predicting recovery trajectories under ecologically valid conditions. Neurophysiological abnormalities persisted beyond clinical recovery given abnormal BG-SA TOJc performance observed when SR-mTBI patients achieved clinical recovery.

Nutritional interventions to improve neurophysiological impairments following traumatic brain injury: A systematic review.

Traumatic brain injury (TBI) accounts for significant global health burden. Effects of TBI can become chronic even following mild injury. There is a need to develop effective therapies to attenuate the damaging effects of TBI and improve recovery outcomes. This literature review using a priori criteria (PROSPERO; CRD42018100623) summarized 43 studies between January 1998 and July 2019 that investigated nutritional interventions (NUT) delivered with the objective of altering neurophysiological (NP) outcomes following TBI. Risk of bias was assessed for included studies, and NP outcomes recorded. The systematic search resulted in 43 of 3,748 identified studies met inclusion criteria. No studies evaluated the effect of a NUT on NP outcomes of TBI in humans. Biomarkers of morphological changes and apoptosis, oxidative stress, and plasticity, neurogenesis, and neurotransmission were the most evaluated NP outcomes across the 43 studies that used 2,897 animals. The risk of bias was unclear in all reviewed studies due to poorly detailed methodology sections. Taking these limitations into account, anti-oxidants, branched chain amino acids, and ω-3 polyunsaturated fatty acids have shown the most promising pre-clinical results for altering NP outcomes following TBI. Refinement of pre-clinical methodologies used to evaluate effects of interventions on secondary damage of TBI would improve the likelihood of translation to clinical populations.

Predicting Sport-related mTBI Symptom Resolution Trajectory Using Initial Clinical Assessment Findings: A Retrospective Cohort Study.

OBJECTIVES: To identify which aspects of initial clinical assessment for sport-related mild traumatic brain injury (SR-mTBI) predict whether an athlete achieves symptom resolution within 14 days of the injury. RESEARCH DESIGN: Retrospective cohort study using prospectively collected data. METHODS: Clinical assessment data were collected from 568 patients diagnosed with SR-mTBI at a single medical clinic between February 2017 and December 2018. Demographic data, medical history, SCAT-5 testing, and physician notes were included in the data set. Data were processed and analysed to identify a shortlist of predictor variables to develop a logistic regression model to discriminate between SR-mTBI symptom resolution that occurred in ≤ 14-days or > 14-days. The data were randomly divided into model development and validation subsamples. The top 15 models were analysed to determine the predictor variables to be included in the final logistic regression model. The final model was then applied to the validation subsample. RESULTS: Half of the athlete participants in this study experienced > 14-day symptom resolution. The final logistic regression model included sex, symptom reporting at initial assessment and presentation with a physiological predominant symptom cluster. The model accounted for 0.90 and 0.85 of the area under the curve and predicted recovery trajectory with 81% and 76% accuracy for the training and validation subsamples, respectively. CONCLUSIONS: Being female, reporting a higher Positive Symptom Total at initial assessment, and being less likely to have a physiological predominant symptom cluster at initial assessment predicted > 14 versus ≤ 14-day SR-mTBI symptom resolution with a high level of accuracy.

Is it really the result of a concussion? Lessons from a case study.

BACKGROUND: Within the last two decades, attitudes have shifted from considering sports-related concussion as an insignificant minor injury with no long-term repercussions to a potentially serious brain injury garnering attention from media, clinicians, researchers, and the general public. OBJECTIVES: To conduct a case study to determine the underlying cause of persistent issues suspected to be associated with a history of sports-related concussion. PROTOCOL: Participant A underwent neurophysiological testing following the Neary protocol (assessment of cerebrovascular and cardiovascular variables), comprehensive concussion assessment at a dedicated sports concussion clinic (history, neurological assessment, cervical spine screening, vestibulo-ocular screening, SCAT-5, and exercise testing), referral to a neurologist, structural MRI scan, and referral for specialised assessment at a dedicated dizziness and balance centre. RESULTS: Despite a history of multiple sports-related concussions, Participant A's persistent symptom reports were associated with peripheral vestibular dysfunction and otolithic dysfunction seemingly unrelated to his concussion history. DISCUSSION: Lessons from Participant A's case study showed that on-going symptoms that patients may associate with the effects of concussions may instead be due to unrelated causes that share similar symptomology. CONCLUSION: This research exemplifies the importance of a multi-disciplinary assessment using a repeated testing protocol.

Implementing a structured exercise program for persistent concussion symptoms: a pilot study on the effects on salivary brain-derived neurotrophic factor, cognition, static balance, and symptom scores.

PRIMARY OBJECTIVE: Persistent concussion symptoms (PCS) affect 10-30% of individuals after sports-related concussion. This study evaluated the effect of exercise-based rehabilitation on symptom scores, brain-derived neurotrophic factor (BDNF), cognitive functions and static balance in a sample of participants with PCS. RESEARCH DESIGN: One group pre-test post-test pilot study. METHODS AND PROCEDURE: Nine participants with PCS received a structured exercise-based rehabilitation program. Changes in symptom scores, BDNF, cognitive functions and measures of static balance were used to evaluate the utility of the exercise program. MAIN OUTCOME AND RESULTS: The results of this pilot study indicate a significant improvement in symptom scores following treatment, as well as some associated benefits in regards to cognitive function and static balance. BDNF levels in the participants with PCS within this study are notably lower than in a previous study on healthy controls. CONCLUSIONS: The preliminary evidence reported in the current pilot study is clinically relevant as our findings suggest exercise-based treatments may improve PCS outcomes in a more favourable manner than rest-based treatment.