Middlebrooks, Erik H

AbstractDBS is an effective neuromodulatory therapy that has been applied in various conditions, including PD, essential tremor, dystonia, Tourette syndrome, and other movement disorders. There have also been recent examples of applications in epilepsy, chronic pain, and neuropsychiatric conditions. Innovations in neuroimaging technology have been driving connectomics, an emerging whole‐brain network approach to neuroscience. Two rising techniques are functional connectivity profiling and structural connectivity profiling. Functional connectivity profiling explores the operational relationships between multiple regions of the brain with respect to time and stimuli. Structural connectivity profiling approximates physical connections between different brain regions through reconstruction of axonal fibers. Through these techniques, complex relationships can be described in various disease states, such as PD, as well as in response to therapy, such as DBS. These advances have expanded our understanding of human brain function and have provided a partial in vivo glimpse into the underlying brain circuits underpinning movement and other disorders. This comprehensive review will highlight the contemporary concepts in brain connectivity as applied to DBS, as well as introduce emerging considerations in movement disorders. © 2020 International Parkinson and Movement Disorder Society

Intracerebral haemorrhage (ICH) describes haemorrhage into the brain parenchyma that may result in a decline of the patient’s neurological function. ICH is a common cause of morbidity and mortality worldwide. Aggressive surgical treatment for ICH has remained controversial as clinical trials have failed to demonstrate substantial improvement in patient outcome and mortality. Recently, promising mechanical and pharmacological minimally invasive surgery (MIS) techniques for the treatment of ICH have been described. MIS was designed with the objective of reducing morbidity due to complications of surgical manipulation. Mechanical MIS includes the use of tubular retractors and small diameter instruments for ICH removal. Pharmacological methods consist of catheter placement inside the haematoma cavity for the passive drainage of the haematoma over the course of several days. One of the most favourable approaches for MIS is the use of natural corridors for reaching the lesion, such as the transsulcal parafascicular approach. This approach provides an anatomical dissection of the subjacent white matter tracts, causing the least amount of damage while evacuating the haematoma. A detailed description of the currently known MIS techniques and devices is presented in this review. Special attention is given to the transsulcal parafascicular approach, which has particular benefits to provide a less traumatic MIS with promising overall patient outcome.

Abstract BACKGROUND The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many pathological conditions. Previous literature has focused on appropriate stimulation targets and their relationships with functional neuroanatomic pathways; however, comprehensive anatomic dissections illustrating these nuclei and their connections are lacking. This information will provide insight into the anatomic basis of stimulation-induced DBS benefits and side effects. OBJECTIVE To combine advanced cadaveric dissection techniques and ultrahigh field magnetic resonance imaging (MRI) to explore the anatomy of the STN, GPi, and PPN with their associated fiber pathways. METHODS A total of 10 cadaveric human brains and 2 hemispheres of a cadaveric head were examined using fiber dissection techniques. The anatomic dissections were compared with 11.1 Tesla (T) structural MRI and 4.7 T MRI fiber tractography. RESULTS The extensive connections of the STN (caudate nucleus, putamen, medial frontal cortex, substantia innominata, substantia nigra, PPN, globus pallidus externus (GPe), GPi, olfactory tubercle, hypothalamus, and mammillary body) were demonstrated. The connections of GPi to the thalamus, substantia nigra, STN, amygdala, putamen, PPN, and GPe were also illustrated. The PPN was shown to connect to the STN and GPi anteriorly, to the cerebellum inferiorly, and to the substantia nigra anteriorly and superiorly. CONCLUSION This study demonstrates connections using combined anatomic microdissections, ultrahigh field MRI, and MRI tractography. The anatomic findings are analyzed in relation to various stimulation-induced clinical effects. Precise knowledge of neuroanatomy, anatomic relationships, and fiber connections of the STN, GPi, PPN will likely enable more effective targeting and improved DBS outcomes.

OBJECTIVEEpilepsy is common among patients with supratentorial brain tumors; approximately 40%–70% of patients with glioma develop brain tumor–related epilepsy (BTRE). Intraoperative localization of the epileptogenic zone during surgical tumor resection (real-time data) may improve intervention techniques in patients with lesional epilepsy, including BTRE. Accurate localization of the epileptogenic signals requires electrodes with high-density spatial organization that must be placed on the cortical surface during surgery. The authors investigated a 360° high-density ring-shaped cortical electrode assembly device, called the “circular grid,” that allows for simultaneous tumor resection and real-time electrophysiology data recording from the brain surface.METHODSThe authors collected data from 99 patients who underwent awake craniotomy from January 2008 to December 2018 (29 patients with the circular grid and 70 patients with strip electrodes), of whom 50 patients were matched-pair analyzed (25 patients with the circular grid and 25 patients with strip electrodes). Multiple variables were then retrospectively assessed to determine if utilization of this device provides more accurate real-time data and improves patient outcomes.RESULTSMatched-pair analysis showed higher extent of resection (p = 0.03) and a shorter transient motor recovery period during the hospitalization course (by approximately 6.6 days, p ≤ 0.05) in the circular grid patients. Postoperative versus preoperative Karnofsky Performance Scale (KPS) score difference/drop was greater for the strip electrode patients (p = 0.007). No significant difference in postoperative seizures between the 2 groups was present (p = 0.80).CONCLUSIONSThe circular grid is a safe, feasible tool that grants direct access to the cortical surgical surface for tissue resection while simultaneously monitoring electrical activity. Application of the circular grid to different brain pathologies may improve intraoperative epileptogenic detection accuracy and functional outcomes, while decreasing postoperative complications.

AbstractBiallelic pathogenic variants in AARS2, a gene encoding the mitochondrial alanyl‐tRNA synthetase, result in a spectrum of findings ranging from infantile cardiomyopathy to adult‐onset progressive leukoencephalopathy. In this article, we present three unrelated individuals with novel compound heterozygous pathogenic AARS2 variants underlying diverse clinical presentations. Patient 1 is a 51‐year‐old man with adult‐onset progressive cognitive, psychiatric, and motor decline and leukodystrophy. Patient 2 is a 34‐year‐old man with childhood‐onset progressive tremor followed by the development of polyneuropathy, ataxia, and mild cognitive and psychiatric decline without leukodystrophy on imaging. Patient 3 is a 57‐year‐old woman with childhood‐onset tremor and nystagmus which preceded dystonia, chorea, ataxia, depression, and cognitive decline marked by cerebellar atrophy and white matter disease. These cases expand the clinical heterogeneity of AARS2‐related disorders, given that the first and third case represent some of the oldest known survivors of this disease, the second is adult‐onset AARS2‐related neurological decline without leukodystrophy, and the third is biallelic AARS2‐related disorder involving a partial gene deletion.

OBJECTIVE Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising therapy for refractory epilepsy. Unfortunately, the variability in outcomes from ANT DBS is not fully understood. In this pilot study, the authors assess potential differences in functional connectivity related to the volume of tissue activated (VTA) in ANT DBS responders and nonresponders as a means for better understanding the mechanism of action and potentially improving DBS targeting. METHODS This retrospective analysis consisted of 6 patients who underwent ANT DBS for refractory epilepsy. Patients were classified as responders (n = 3) if their seizure frequency decreased by at least 50%. The DBS electrodes were localized postoperatively and VTAs were computationally generated based on DBS programming settings. VTAs were used as seed points for resting-state functional MRI connectivity analysis performed using a control dataset. Differences in cortical connectivity to the VTA were assessed between the responder and nonresponder groups. RESULTS The ANT DBS responders showed greater positive connectivity with the default mode network compared to nonresponders, including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobule, and precuneus. Interestingly, there was also a consistent anticorrelation with the hippocampus seen in responders that was not present in nonresponders. CONCLUSIONS Based on their pilot study, the authors observed that successful ANT DBS in patients with epilepsy produces increased connectivity in the default mode network, which the authors hypothesize increases the threshold for seizure propagation. Additionally, an inhibitory effect on the hippocampus mediated through increased hippocampal γ-aminobutyric acid (GABA) concentration may contribute to seizure suppression. Future studies are planned to confirm these findings.

When medically intractable epilepsy is multifocal or focal but poorly localized, neuromodulation can be useful therapy. One such technique is deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT). Unfortunately, the ANT is difficult to visualize in standard MRI sequences and its indirect targeting is difficult because of thalamic variability and atrophy in patients with epilepsy. The following study describes the novel use of the fast gray matter acquisition T1 inversion recovery (FGATIR) MRI sequence to delineate the mammillothalamic tract for direct targeting of the ANT through visualizing the termination of the mammillothalamic tract in the ANT. The day prior to surgery in a 19-year-old, right-handed woman with a 5-year history of epilepsy, MRI was performed on a 3-T Siemens Prisma scanner (Siemens AG, Healthcare Sector) using a 64-channel head and neck coil. As part of the imaging protocol, noncontrast magnetization-prepared rapid gradient echo (MP-RAGE) and diffusion tensor imaging (DTI) sequences were obtained for targeting purposes. The ANT was directly targeted using the FGATIR sequence, and bilateral Medtronic 3389 leads were placed. At the last follow-up (2 months), the patient reported an approximate 75% decrease in seizure frequency, as well as a decrease in seizure severity.