Middlebrooks, Erik H.

AbstractThe pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

ABSTRACTObjectivesThe aim of this study is to identify anatomical regions related to stimulation‐induced dyskinesia (SID) after pallidal deep brain stimulation (DBS) in Parkinson's disease (PD) patients and to analyze connectivity associated with SID.MethodsThis retrospective study analyzed the clinical and imaging data of PD patients who experienced SID during the monopolar review after pallidal DBS. We analyzed structural and functional connectivity using normative connectivity data with the volume of tissue activated (VTA) modeling. Each contact was assigned to either that producing SID (SID VTA) or that without SID (non‐SID VTA). Structural and functional connectivity was compared between SID and non‐SID VTAs. “Optimized VTAs” were also estimated using the DBS settings at 6 months after implantation.ResultsOf the 68 consecutive PD patients who underwent pallidal implantation, 20 patients (29%) experienced SID. SID VTAs were located more dorsally and anteriorly compared with non‐SID and optimized VTAs and were primarily in the dorsal globus pallidus internus (GPi) and dorsal globus pallidus externus (GPe). SID VTAs showed significantly higher structural connectivity than non‐SID VTAs to the associative cortex and supplementary motor area/premotor cortex (P < 0.0001). Simultaneously, non‐SID VTAs showed greater connectivity to the primary sensory cortex, cerebellum, subthalamic nucleus, and motor thalamus (all P < 0.0004). Functional connectivity analysis showed significant differences between SID and non‐SID VTAs in multiple regions, including the primary motor, premotor, and prefrontal cortices and cerebellum.ConclusionSID VTAs were primarily in the dorsal GPi/GPe. The connectivity difference between the motor‐related cortices and subcortical regions may explain the presence and absence of SID. © 2020 International Parkinson and Movement Disorder Society

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.