Faculty Bibliography

Patients with a history of mild traumatic brain injury (post-mTBI-patients) may have enduring cardiovascular-autonomic dysregulation and emotional problems. Olfactory stimulation (OS) triggers emotional and cardiovascular-autonomic responses which might be compromised in post-mTBI-patients. We therefore evaluated these responses to OS in post-mTBI-patients. In 17 post-mTBI-patients (interval since mTBI 32.4±6.8 months) and 17 age- and sex-matched controls, we recorded respiration, electrocardiographic RR-intervals, systolic, diastolic blood pressures (BPsys, BPdia) before and during pleasant vanilla-stimulation and unpleasant hydrogen-sulphide-(H2S)-stimulation. Participants rated OS related pleasantness, arousal, intensity, and familiarity on 9-point Likert-scales. ANOVAs with post-hoc analyses compared parameters within each group before and during OS. To assess associations between pleasantness, arousal, intensity, and familiarity, we correlated OS-scores within groups (significance: p<0.05). Baseline parameters were similar between groups. Only in controls, vanilla-stimulation significantly lowered BPsys and BPdia, while H2S-stimulation lowered RR-intervals. Vanilla related pleasantness-scores were lower, intensity-scores were higher in patients than controls. During vanilla-stimulation, pleasantness-scores correlated negatively with arousal-scores in controls, while familiarity-scores correlated positively with intensity-scores in patients. During H2S-stimulation, familiarity-scores correlated negatively with pleasantness-scores in controls, while pleasantness-scores correlated negatively with arousal-scores in mTBI patients. Post-mTBI-patients could not change blood pressure or RR-intervals during OS but perceived vanilla stimuli as less pleasant and more intense than did controls. Associations between pleasantness, arousal, intensity, and familiarity differed between groups suggesting different activation of the olfactory network and the central autonomic network upon OS. Subtle lesions within these networks might cause persistent changes in emotional and cognitive odor perception and cardiovascular responses.

In this work, we propose bag of adversarial features (BAF) for identifying mild traumatic brain injury (MTBI) patients from their diffusion magnetic resonance images (MRI) (obtained within one month of injury) by incorporating unsupervised feature learning techniques. MTBI is a growing public health problem with an estimated incidence of over 1.7 million people annually in US. Diagnosis is based on clinical history and symptoms, and accurate, concrete measures of injury are lacking. Unlike most of previous works, which use hand-crafted features extracted from different parts of brain for MTBI classification, we employ feature learning algorithms to learn more discriminative representation for this task. A major challenge in this field thus far is the relatively small number of subjects available for training. This makes it difficult to use an end-to-end convolutional neural network to directly classify a subject from MR images. To overcome this challenge, we first apply an adversarial auto-encoder (with convolutional structure) to learn patch-level features, from overlapping image patches extracted from different brain regions. We then aggregate these features through a bag-of-word approach. We perform an extensive experimental study on a dataset of 227 subjects (including 109 MTBI patients, and 118 age and sex matched healthy controls), and compare the bag-of-deep-features with several previous approaches. Our experimental results show that the BAF significantly outperforms earlier works relying on the mean values of MR metrics in selected brain regions.

Case Description: The patient is a 68-year-old female with a history of post-concussion syndrome after a fall in 2012 with loss of consciousness. Her primary symptoms included vertigo, headaches, anxiety, and impaired balance. Her symptoms intermittently improved with vestibular therapy and repeated Epley maneuvers. Six years later she had another concussion and experienced exacerbation of symptoms, which gradually improved, however was also reporting left ear tinnitus that was pulsatile in character. Physical examination in office did not show any focal neurological deficits or gross ear abnormalities. MRA brain revealed a left transverse and sigmoid sinus dural arteriovenous fistula.
Setting(s): Outpatient office Patient: 68-year-old female with history of post-concussion syndrome presented with pulsatile tinnitus of left ear. Assessment/Results: Patient underwent uncomplicated coil embolization with interventional radiology with ultimate resolution of tinnitus and improvement in headaches after the procedure.
Discussion(s): Vestibular symptoms such as hearing loss, dizziness, vertigo, and tinnitus are common after a mild brain injury and fall under the diagnosis of labyrinthine concussion. Symptoms can occur even without radiologic evidence of injury to the labyrinth. In any patient with tinnitus and a history of concussion, post-concussion syndrome is high on the differential. However, it is important for providers to consider other possible causes. This is especially true for pulsatile tinnitus, which accounts for less than 10% of tinnitus patients and is often caused by vascular malformations.
Conclusion(s): Patients with post-concussion syndrome endorse a myriad of symptoms which may be sequela of prior brain injury, but providers must consider alternative etiologies of symptoms. In this case, workup of pulsatile tinnitus in such a patient led to appropriate diagnosis and treatment of dural AV fistula and subsequent resolution of the patient's symptoms

BACKGROUND AND PURPOSE/OBJECTIVE:Working memory impairment is one of the most troubling and persistent symptoms after mild traumatic brain injury (MTBI). Here we investigate how working memory deficits relate to detectable WM microstructural injuries to discover robust biomarkers that allow early identification of patients with MTBI at the highest risk of working memory impairment. MATERIALS AND METHODS/METHODS:Multi-shell diffusion MR imaging was performed on a 3T scanner with 5 b-values. Diffusion metrics of fractional anisotropy, diffusivity and kurtosis (mean, radial, axial), and WM tract integrity were calculated. Auditory-verbal working memory was assessed using the Wechsler Adult Intelligence Scale, 4th ed, subtests: 1) Digit Span including Forward, Backward, and Sequencing; and 2) Letter-Number Sequencing. We studied 19 patients with MTBI within 4 weeks of injury and 20 healthy controls. Tract-Based Spatial Statistics and ROI analyses were performed to reveal possible correlations between diffusion metrics and working memory performance, with age and sex as covariates. RESULTS:= .04), mainly present in the right superior longitudinal fasciculus, which was not observed in healthy controls. Patients with MTBI also appeared to lose the normal associations typically seen in fractional anisotropy and axonal water fraction with Letter-Number Sequencing. Tract-Based Spatial Statistics results also support our findings. CONCLUSIONS:Differences between patients with MTBI and healthy controls with regard to the relationship between microstructure measures and working memory performance may relate to known axonal perturbations occurring after injury.

BACKGROUND AND PURPOSE/OBJECTIVE:Na) MR imaging. MATERIALS AND METHODS/METHODS:Na) MR imaging using a 3T scanner. Total sodium concentration was measured in the genu, body, and splenium of the corpus callosum with 5-mm ROIs; total sodium concentration of the genu-to-splenium ratio was calculated and compared between patients and controls. RESULTS:= .001). CONCLUSIONS:Complex differences are seen in callosal total sodium concentration in symptomatic patients with mild traumatic brain injury, supporting the notion of ionic dysfunction in the pathogenesis of mild traumatic brain injury. The total sodium concentration appears to be altered beyond the immediate postinjury phase, and further work is needed to understand the relationship to persistent symptoms and outcome.

As healthcare continues to evolve, there are changes in the delivery of care for patients with severe neurologic injuries. Although the acute hospital stay is shortening, physiatrists can play a key role in preparing patients for rehabilitation, minimizing longer-term complications and helping to determine the most appropriate paths for further treatment. Inpatient rehabilitation facilities (IRFs) continue to be an important part of the care continuum for patients with severe injuries, but the role of IRFs has also evolved as patients have been admitted with increasing medical and neurologic complexity and length of stay continues to be reduced. Skilled nursing facilities and subacute facilities continue to evolve, in part to fill the gaps that have developed for patients who are "not yet ready for rehabilitation" and for those whose recovery trajectory has been deemed too slow for IRF. Outpatient care is also changing, in part due to the availability of new rehabilitation interventions as highlighted in other sections of the supplement. Furthermore, telemedicine will provide additional options for expanding specialized care beyond prior geographical limitations. Physiatrists need to be aware of these ongoing changes and the roles that they can play outside of the traditional IRF model of care. This article will focus on the innovations in healthcare delivery and opportunities to maximize outcomes in the current and future models of care.

Mild traumatic brain injury is a growing public health problem with an estimated incidence of over 1.7 million people annually in US. Diagnosis is based on clinical history and symptoms, and accurate, concrete measures of injury are lacking. This work aims to directly use diffusion MR images obtained within one month of trauma to detect injury, by incorporating deep learning techniques. To overcome the challenge due to limited training data, we describe each brain region using the bag of word representation, which specifies the distribution of representative patch patterns. We apply a convolutional auto-encoder to learn the patch-level features, from overlapping image patches extracted from the MR images, to learn features from diffusion MR images of brain using an unsupervised approach. Our experimental results show that the bag of word representation using patch level features learnt by the auto encoder provides similar performance as that using the raw patch patterns, both significantly outperform earlier work relying on the mean values of MR metrics in selected brain regions.

OBJECTIVE:After traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation. METHODS:In 51 post-moderate-severe-TBI patients (32.7 ± 10.5 years old, 43.1 ± 33.4 months post-injury), and 30 controls (29.1 ± 9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05). RESULTS:At rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter. CONCLUSIONS:In post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation. SIGNIFICANCE/CONCLUSIONS:Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI.

We seek to elucidate the underlying pathophysiology of injury sustained after mild traumatic brain injury (MTBI) using multi-shell diffusion MRI, deriving compartment-specific WM tract integrity (WMTI) metrics. WMTI allows a more biophysical interpretation of WM changes by describing microstructural characteristics in both intra- and extra-axonal environments. Thirty-two patients with MTBI within 30 days of injury and twenty-one age- and sex-matched controls were imaged on a 3T MR scanner. Multi-shell diffusion acquisition was performed with 5 b-values (250 - 2500 s/mm²) along 6 - 60 diffusion encoding directions. Tract-based spatial statistics (TBSS) was used with family-wise error (FWE) correction for multiple comparisons. TBSS results demonstrate focally lower intra-axonal diffusivity (D_axon) in MTBI patients in the splenium of the corpus callosum (sCC) (p < 0.05, FWE-corrected). The Area Under the Curve (AUC)-value for was 0.76 with low sensitivity of 46.9%, but 100% specificity. These results indicate that D_axon may be a useful imaging biomarker highly specific for MTBI-related WM injury. The observed decrease in D_axon suggests restriction of the diffusion along the axons occurring shortly after injury.