Faculty Bibliography

In collaboration with the American Academy of Pediatrics, Child Neurology Society, and Society for Critical Care Medicine, the American Academy of Neurology formulated an updated, evidence-informed consensus-based guideline for pediatric and adult brain death/death by neurologic criteria (BD/DNC) determination. In comparison with the prior guidelines, the revisions and additions in this guideline, which are summarized in this review, are intended to (1) ensure recommendations are conservative, yet practical, and emphasize circumstances in which BD/DNC determination should be delayed or deferred, so as to minimize the risk of a false-positive BD/DNC determination; and (2) provide guidance about aspects of BD/DNC determination that clinicians find challenging and/or controversial. We hope that clinicians throughout the United States will use this information to revise their hospital BD/DNC determination policies to conform to the standardized process for BD/DNC determination described in the new guideline, to ensure that every BD/DNC evaluation is consistent and accurate.

BACKGROUND AND OBJECTIVES/UNASSIGNED: METHODS/UNASSIGNED:variants were recruited through physicians' practices and patient organization groups. We used standardized questionnaires to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder and adaptive skills of patients. We also assessed caregiver burden. RESULTS/UNASSIGNED:de novo variants. One patient with a partial exon 3 deletion had greater daily living skills and social skills than others with single-nucleotide variants. Ten of 14 (71%) patients had drug-resistant seizures, treated with a median of 2 antiseizure medications. All patients (100%) had abnormal pain processing. Sleep disturbances, social communication disorders, and aggressive/self-injurious behaviors were each reported in 86% of patients. Only half of adults could walk with minimal or no assistance. Toileting was normal in 29%, and 71% had constipation. No adult patients could read or understand verbal material at a sixth-grade level or higher. Aggressive/self-injurious behaviors were leading cause of caregiver burden. The oldest patient was aged 65 years; although nonambulant, she had walked independently when younger. DISCUSSION/UNASSIGNED:-DEE. Only 50% of adults can ambulate with minimal or no assistance. Almost all adult patients depend on caregivers for many activities of daily living. Prompt diagnostic genetic testing of adults with DEE can inform clinical care and guide outcomes of precision therapies.

Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and the complexity of bioinformatic analysis. Here we report the use of virus capture-based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Thirty-four samples were categorized: (1) patients with definitive CNS infection by routine testing; (2) patients meeting clinically the Brighton criteria (BC) for meningoencephalitis; (3) patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT, and DNA extracts were used for BacCapSeq analysis. Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3, 11/26 samples (42%) were positive for at least one pathogen; however, 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess the clinical value of this novel technique, clinicians should understand the benefits and limitations of using this modality.

BACKGROUND:The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS:We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS:Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS:More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

Anatomical studies in animals and imaging studies in humans show that cerebral sensorimotor areas map onto corresponding cerebellar sensorimotor areas and that cerebral association areas map onto cerebellar posterior lobe regions designated as the representation of the association (cognitive and limbic) cerebellum. We report a patient with unilateral left hemispheric status epilepticus, whose brain MRI revealed diffuse unihemispheric cerebral cortical FLAIR and diffusion signal hyperintensity but spared primary motor, somatosensory, visual, and to lesser extent auditory cerebral cortices. Crossed cerebellar diaschisis (dysfunction at a site remote from, but connected to, the location of the primary lesion) showed signal hyperintensity in the right cerebellar posterior lobe and lobule IX, with sparing of the anterior lobe, and lobule VIII. This unique topographic pattern of involvement and sparing of cerebral and cerebellar cortical areas matches the anatomical and functional connectivity specialization in the cerebrocerebellar circuit. This first demonstration of within-hemispheric specificity in the areas affected and spared by cerebrocerebellar diaschisis provides further confirmation in the human brain for topographic organization of connections between the cerebral hemispheres and the cerebellum.

In continuation of our earlier work (Chen & Sreenivasan, J. Fluid Mech., vol. 908, 2021, R3; Chen & Sreenivasan, J. Fluid Mech., vol. 933, 2022a, A20 - together referred to as CS hereafter), we present a self-consistent Reynolds number asymptotics for wall-normal profiles of variances of streamwise and spanwise velocity fluctuations as well as root-mean-square pressure, across the entire flow region of channel and pipe flows and flat-plate boundary layers. It is first shown that, when normalized by peak values, the Reynolds number dependence and wall-normal variation of all three profiles can be decoupled, in excellent agreement with available data, sharing the common inner expansion of the type, where is one of the quantities just mentioned, the functions and depend only on, and is the friction Reynolds number. Here, the superscript indicates normalization by wall variables. We show that this result is completely consistent with CS. Secondly, by matching the above inner expansion and the outer flow similarity form, a bounded variation is derived for the outer region where, for each, the constants and are independent of and - also in excellent agreement with simulations and experimental data. One of the predictions of the analysis is that, for asymptotically high Reynolds numbers, a finite plateau appears in the outer region. This result sheds light on the intriguing issue of the outer shoulder of the variance of the streamwise velocity fluctuation, which should be bounded by the asymptotic plateau of approximately 10.

OBJECTIVE:Despite widespread use of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF), it is surprisingly understudied among adults with attention-deficit/hyperactivity disorder (ADHD). This is significant as ADHD is a frequent referral for neuropsychological evaluation; however, the core symptom of attention difficulty is a nonspecific sequela of many psychological disorders. This study aimed to characterize MMPI-2-RF profiles among adults with ADHD and examine the effect of comorbid psychopathology. METHOD/METHODS:A large, demographically diverse sample of 413 consecutive adults referred for neuropsychological evaluation to assist with differential diagnosis of ADHD who completed the MMPI-2-RF was examined. Profiles of the 145 patients diagnosed with ADHD-only were compared to 192 with ADHD and a comorbid psychological disorder and a 55-patient non-ADHD psychiatric comparison group. Among the ADHD-only group, profiles also were compared based on ADHD-presentation type (Predominantly Inattentive vs. Combined presentation). RESULTS:The ADHD/psychopathology and psychiatric comparison groups scored higher than the ADHD-only group across nearly all scales with widespread clinical elevations. Conversely, the ADHD-only group displayed an isolated elevation on the Cognitive Complaints scale. Comparison between ADHD presentations revealed several small-moderate significant differences, the largest of which occurred on the Externalizing and Interpersonal scales. CONCLUSIONS:Adults with ADHD alone, and no other psychopathology have a unique MMPI-2-RF profile characterized by isolated elevation on the Cognitive Complaints scale. These results support use of the MMPI-2-RF in assessment of adults with ADHD as it can help distinguish ADHD alone from ADHD/comorbid psychopathology and identify relevant psychiatric comorbidities that may be contributing to patients' inattention complaints.

BACKGROUND/UNASSIGNED:) stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect. METHODS/UNASSIGNED:). We used a "backward looking" trajectory approach. Patients were aligned according to the time of outcome occurrence and the trajectory of each variable was assessed prior to that outcome by accounting for both cases and non-cases. RESULTS/UNASSIGNED:Of 635 patients, 49% were female, and mean age was 69 years. Thirty five percent of patients had MLS ≥ 5mm, 24.1% had PGS >4mm, and DHC occurred in 10.7%. For the three outcomes of interest, backward-looking trajectories showed mild increases in white blood cell count (10 up to 11 K/UL within 72 hours), temperature (up to half a degree within 24 hours), and sodium (1-3 mEq/L within 24 hours) leading up to outcomes. We also observed a decrease in heart rate (75 - 65 beats per minute) 24 hours prior to DHC. CONCLUSIONS/UNASSIGNED:Univariable longitudinal profiling showed that temperature, white blood cell count, and sodium increase prior to radiographic and clinical indicators of space-occupying mass effect. These findings will inform development of multivariable dynamic risk models to aid prediction of life-threatening space-occupying mass effect.

Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.