The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin

Acta Neurochirurgica (2020) 162: 1053–1066

Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained. We here report the results of an uncontrolled case series of patients with refractory tremor who underwent deep brain stimulation under tractographic assistance.

Methods A total of 36 patients were enrolled (essential tremor (17), Parkinson’s tremor (8), multiple sclerosis (7), dystonic head tremor (3), tardive dystonia (1)) and received 62 DBS electrodes (26 bilateral; 10 unilateral). Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1Wand T2W sequences. The DRTwas individually tracked and used as a direct thalamic or subthalamic target. Intraoperative tremor reduction was graded on a 4-point scale (0 = no tremor reduction to 3 = full tremor control) and recorded together with the current amplitude, respectively. Stimulation point coordinates were recorded and compared to DRT. The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement per current ratio).

Results Stimulation points of 241 were available for analysis. A total of 68 trajectories were tested (62 dB leads, 1.1 trajectories tested per implanted lead). Tremor improvement was significantly decreasing (p < 0.01) if the distance to both the border and the center of the DRT was increasing. On the initial trajectory, 56 leads (90.3%) were finally placed. Long-term outcomes were not part of this analysis.

Discussion Tremor of various origins was acutely alleviated at different points along the DRT fiber tract (above and below the MCP plane) despite different tremor diseases. DRT is potentially a common tremor-reducing structure. Individual targeting helps to reduce brain penetrating tracts. TiCR characterizes stimulation efficacy and might help to identify an optimal stimulation point.

The striking effects of deep cerebellar stimulation on generalized fixed dystonia

J Neurosurg 132:712–716, 2020

Cerebellar neuromodulation could influence the pathological abnormalities of movement disorders through several connections between the cerebellum and the basal ganglia or other cortices. In the present report, the authors demonstrate the effects of cerebellar deep brain stimulation (DBS) on a patient with severe generalized fixed dystonia (FD) that was refractory to bilateral pallidotomy and intrathecal baclofen therapy.

A previously healthy 16-year-old girl presented with generalized FD. Bilateral pallidotomy and intrathecal baclofen therapy had failed to resolve her condition, following which she received DBS through the bilateral superior cerebellar peduncle (SCP) and dentate nucleus (DN). Ipsilateral stimulation of the SCP or DN improved the FD, and the ability of DBS administered via the SCP to relax muscles was better than that of DN DBS.

A considerable improvement of generalized FD, from a bedridden state to a wheelchairbound state, was observed in the patient following 6 months of chronic bilateral DBS via the SCP; moreover, the patient was able to move her arms and legs. The findings in the present case suggest that neuromodulation of deep cerebellar structures is a promising treatment for FD that is refractory to conventional treatments.

Deep brain stimulation of the globus pallidus internus versus the subthalamic nucleus in isolated dystonia

J Neurosurg 132:721–732, 2020

Surgical procedures involving deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) are well-established treatments for isolated dystonia. However, selection of the best stimulation target remains a matter of debate. The authors’ objective was to compare the effectiveness of DBS of the GPi and the STN in patients with isolated dystonia.

METHODS In this matched retrospective cohort study, the authors searched an institutional database for data on all patients with isolated dystonia who had undergone bilateral implantation of DBS electrodes in either the GPi or STN in the period from January 30, 2014, to June 30, 2017. Standardized assessments of dystonia and health-related quality of life using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and SF-36 were conducted before and at 1, 6, and 12 months after surgery. No patients were lost to the 6-month follow-up; 5 patients were lost to the 12-month follow-up.

RESULTS Both GPi (14 patients) and STN (16 patients) stimulation produced significant improvement in dystonia and quality of life in all 30 patients found in the database search. At the 1-month follow-up, however, the percentage improvement in the BFMDRS total movement score was significantly (p = 0.01) larger after STN DBS (64%) than after GPi DBS (48%). At the 12-month follow-up, the percentage improvement in the axis subscore was significantly (p = 0.03) larger after GPi DBS (93%) than after STN DBS (83%). Also, the total amount of electrical energy delivered was significantly (p = 0.008) lower with STN DBS than with GPi DBS (124 ± 52 vs 192 ± 65 mJ, respectively).

CONCLUSIONS The GPi and STN are both effective targets in alleviating dystonia and improving quality of life. However, GPi stimulation may be better for patients with axial symptoms. Moreover, STN stimulation may produce a larger clinical response within 1 month after surgery and may have a potential economic advantage in terms of lower battery consumption.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences

J Neurosurg 132:586–594, 2020

Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients’ accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research.

METHODS A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from “the worst” to “the most common.” In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed.

RESULTS In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event.

CONCLUSIONS Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

 

Nucleus basalis of Meynert neuronal activity in Parkinson’s disease

J Neurosurg 132:574–582, 2020

Neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer’s disease and Parkinson’s disease (PD). In nonhuman primates, the nbM firing pattern (5–40 Hz) has also been correlated with working memory and sustained attention. In this study, authors performed microelectrode recordings of the globus pallidus pars interna (GPi) and the nbM immediately prior to the implantation of bilateral deep brain stimulation (DBS) electrodes in PD patients to treat motor symptoms and cognitive impairment, respectively. Here, the authors evaluate the electrophysiological properties of the nbM in patients with PD.

METHODS Five patients (4 male, mean age 66 ± 4 years) with PD and mild cognitive impairment underwent bilateral GPi and nbM DBS lead implantation. Microelectrode recordings were performed through the GPi and nbM along a single trajectory. Firing rates and burst indices were characterized for each neuronal population with the patient at rest and performing a sustained-attention auditory oddball task. Action potential (AP) depolarization and repolarization widths were measured for each neuronal population at rest.

RESULTS In PD patients off medication, the authors identified neuronal discharge rates that were specific to each area populated by GPi cells (92.6 ± 46.1 Hz), border cells (34 ± 21 Hz), and nbM cells (13 ± 10 Hz). During the oddball task, firing rates of nbM cells decreased (2.9 ± 0.9 to 2.0 ± 1.1 Hz, p < 0.05). During baseline recordings, the burst index for nbM cells (1.7 ± 0.6) was significantly greater than those for GPi cells (1.2 ± 0.2, p < 0.05) and border cells (1.1 ± 0.1, p < 0.05). There was no significant difference in the nbM burst index during the oddball task relative to baseline (3.4 ± 1.7, p = 0.20). With the patient at rest, the width of the depolarization phase of APs did not differ among the GPi cells, border cells, and nbM cells (p = 0.60); however, during the repolarization phase, the nbM spikes were significantly longer than those for GPi high-frequency discharge cells (p < 0.05) but not the border cells (p = 0.20).

CONCLUSIONS Neurons along the trajectory through the GPi and nbM have distinct firing patterns. The profile of nbM activity is similar to that observed in nonhuman primates and is altered during a cognitive task associated with cholinergic activation. These findings will serve to identify these targets intraoperatively and form the basis for further research to characterize the role of the nbM in cognition.

Stereotactic Lesion in the Forel’s Field H: A Two-Years Prospective Open-Label Study on Motor and Nonmotor Symptoms, Neuropsychological Functions and Quality of Life in Parkinson Disease

Neurosurgery, Volume 85, Issue 4, October 2019, Pages E650–E659

Stereotactic lesion in the Forel’s field H (campotomy) was proposed in 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on this approach have emerged. Additionally, no study has assessed its effects on nonmotor symptoms, neuropsychological functions and quality of life.

OBJECTIVE: To provide a prospective 2-yr assessment of motor, nonmotor, neuropsychological and quality of life variables after unilateral campotomy.

METHODS: Twelve PD patients were prospectively evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson’s disease quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, neuropsychiatric, neuropsychological and quality of life variables were assessed. The impact of PD on global health was also rated.

RESULTS: A significant reduction in contralateral rest tremor (65.7%, P < .001), rigidity (87.8%, P < .001), bradykinesia (68%, P < .001) and axial symptoms (24.2%, P < .05) in offmedication condition led to a 43.9% reduction in UPSDRS III scores 2 yr after campotomy (P < .001). Gait improved by 31.9% (P < .05) and walking time to cover 7 m was reduced by 43.2% (P< .05). Pain decreased by 33.4% (P< .01), while neuropsychiatric and neuropsychological functions did not change. Quality of life improved by 37.8% (P < .05), in line with a 46.7% reduction of disease impact on global health (P < .001).

CONCLUSION: A significant 2-yr improvement of motor symptoms, gait performance and pain was obtained after unilateral campotomy without significant changes to cognition. Quality of life markedly improved in parallel with a significant reduction of PD burden on global health.

Fully endoscopic microvascular decompression for hemifacial spasm

J Neurosurg 131:813–819, 2019

Hemifacial spasm (HFS) is characterized by involuntary tonic and/or clonic contractions of facial nerve muscles. Fully endoscopic microvascular decompression (E-MVD) for HFS has not been widely adopted. This paper aims to illustrate the safety and efficacy of the fully endoscopic technique for HFS treatment.

METHODS The authors conducted a single-center retrospective study of 27 patients (28 separate E-MVD cases; 1 patient had bilateral E-MVD) diagnosed with HFS who underwent fully E-MVD from January 2013 to October 2016. Intraoperative brainstem auditory evoked potentials and lateral spread resolution were reviewed. Outcome was based on the clinical status of the patient at the last contact point with the senior author. Complications were categorized as facial weakness, hearing loss, ataxia, dysphagia, or any adverse event able to be attributed to the surgical procedure.

RESULTS HFS was relieved either completely or partially in the majority of cases (24 of 28, 85.7%). Of the 28 separate procedures, 17 (60.7%) resulted in complete resolution of symptoms, 4 (14.3%) resulted in near-complete resolution, 2 (7.1%) resulted in 50% reduction of symptoms, 1 (3.6%) resulted in minimal reduction, and 4 (14.3%) resulted in no relief. Of the 27 patients, 26 (96%) had no permanent postoperative complications. In multivariate logistic regression, the best predictor of greater than 50% resolution of spasm was resolution of intraoperative lateral spread response.

CONCLUSIONS A fully E-MVD for HFS provides a safe and comprehensive view of the neurovascular conflict. Exclusive use of the endoscope in MVD is both safe and feasible in the treatment of HFS. Attention to lateral spread response monitoring remains an integral part of comprehensive neurosurgical management.

Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation

Neurosurgery, Volume 85, Issue 3, September 2019:  E430–E439

Therapeutic brain stimulation has proven efficacious for treatment of nervous system diseases, exerting widespread influence via disease-specific neural networks. Activation or suppression of neural networks could theoretically be assessed by either clinical symptom modification (ie, tremor, rigidity, seizures) or development of specific biomarkers linked to treatment of symptomatic disease states.

For example, biomarkers indicative of disease state could aid improved intraoperative localization of electrode position, optimize device efficacy or efficiency through dynamic control, and eventually serve to guide automatic adjustment of stimulation settings.

Biomarkers to control either extracranial or intracranial stimulation span from continuous physiological brain activity, intermittent pathological activity, and triggered local phenomena or potentials, to wearable devices, blood flow, biochemical or cardiac signals, temperature perturbations, optical or magnetic resonance imaging changes, or optogenetic signals.

The goal of this review is to update new approaches to implement control of stimulation through relevant biomarkers. Critical questions include whether adaptive systems adjusted through biomarkers can optimize efficiency and eventually efficacy, serve as inputs for stimulation adjustment, and consequently broaden our fundamental understanding of abnormal neural networks in pathologic states.

Neurosurgeons are at the forefront of translating and developing biomarkers embedded within improved brain stimulation systems. Thus, criteria for developing and validating biomarkers for clinical use are important for the adaptation of device approaches into clinical practice.

Machine learning—aided personalized DTI tractographic planning for deep brain stimulation of the superolateral medial forebrain bundle using HAMLET

Acta Neurochirurgica (2019) 161:1559–1569

Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI definition), and has to be regarded as subjective. We aimed to develop an objective but patient-specific tracking of the slMFB which at the same time allows the use of a commercial surgical planning system in the context of deep brain stimulation.

Methods The HAMLET (Hierarchical Harmonic Filters for Learning Tracts from Diffusion MRI) machine learning approach was introduced into the standardized workflow of slMFB DBS tractographic planning on the basis of patientspecific dMRI. Rendition of the slMFB with HAMLET serves as an objective comparison for the refinement of the deterministic tracking procedure. Our application focuses on the tractographic planning of DBS (N = 8) for major depression and OCD.

Results Previous results have shown that only fibers belonging to the ventral tegmental area to prefrontal/orbitofrontal axis should be targeted. With the proposed technique, the deterministic tracking approach, that serves as the surgical planning data, can be refined, over-sprouting fibers are eliminated, bundle thickness is reduced in the target region, and thereby probably a more accurate targeting is facilitated. The HAMLET-driven method is meant to achieve a more objective surgical fiber display of the slMFB with deterministic tractography.

Conclusions The approach allows overlying the results of patient-specific planning from two different approaches (manual deterministic and machine learningHAMLET). HAMLET shows the slMFB as a volume and thus serves as an objective tracking corridor. It helps to refine results from deterministic tracking in the surgical workspace without interfering with any part of the standard software solution. We have now included this workflow in our daily clinical experimental work on slMFB DBS for psychiatric indications.

Dorsal anterior cingulate cortex (ACC) deep brain stimulation (DBS): a promising surgical option for the treatment of refractory thalamic pain syndrome (TPS)

Acta Neurochirurgica (2019) 161:1579–1588

Neuroimaging evidences and previous successful case series of cingulotomy for cancer pain have disclosed the key- role of the dorsal anterior cingulate cortex (ACC) in the generation of the empathic and affective dimension of pain. The aim of this study is to assess the effectiveness and safety of ACC neuromodulation for the treatment of the thalamic pain syndrome (TPS), a chronic neuropathic disease often complicated by severe affective and emotional distress in the long term.

Method From January 2015 to April 2017, 5 patients with pure drug-refractory TPS underwent ACC deep brain stimulation (DBS) at our institution. Quantitative assessment of pain and health-related quality of life were performed 1 day before surgery and postoperatively at 6 and 18 months by using the numeric rating scale (NRS), the 36-item short-form health survey (SF-36), and the McGill pain and the EuroQol5-domain questionnaires.

Results Mean age at surgery was 56.2 years (range, 47–66). NRS score improved by 37.9% at 6 months (range, − 22.2 to − 80%) and by 35% at 18 months (range, − 11.1 to − 80%). At the last follow-up, one patient reported a relevant pain reduction (NRS 2), only complaining of mild pain poorly interfering with activities of daily living. Concomitant improvements in the McGill and EuroQol5-domain pain questionnaires, SF-36 total and sub-item scores were also noticed at each follow-up. No surgical or stimulation-related complications occurred during the study period.

Conclusions ACC DBS may be a safe and promising surgical option to alleviate discomfort and improve the overall quality of life in a patient affected by drug-resistant TPS. Further prospective, larger, and randomized studies are needed to validate these findings.

Results of Gamma Knife anterior capsulotomy for refractory obsessive-compulsive disorder

J Neurosurg 131:376–383, 2019

Obsessive-compulsive disorder (OCD) is a severe psychiatric condition. The authors present their experience with Gamma Knife radiosurgery (GKRS) in the treatment of patients with OCD resistant to any medical therapy.

METHODS Patients with severe OCD resistant to all pharmacological and psychiatric treatments who were treated with anterior GKRS capsulotomy were retrospectively reviewed. These patients were submitted to a physical, neurological, and neuropsychological examination together with structural and functional MRI before and after GKRS treatment. Strict study inclusion criteria were applied. Radiosurgical capsulotomy was performed using two 4-mm isocenters targeted at the midputaminal point of the anterior limb of the capsule. A maximal dose of 120 Gy was prescribed for each side. Clini- cal global changes were assessed using the Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) scale, EQ-5D, Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI). OCD symptoms were determined by the Yale–Brown Obsessive Compulsive Scale (Y-BOCS).

RESULTS Ten patients with medically refractory OCD (5 women and 5 men) treated between 2006 and 2015 were included in this study. Median age at diagnosis was 22 years, median duration of illness at the time of radiosurgery was 14.5 years, and median age at treatment was 38.8 years. Before GKRS, the median Y-BOCS score was 34.5 with a me- dian obsession score of 18 and compulsion score of 17. Seven (70%) of 10 patients achieved a full response at their last follow-up, 2 patients were nonresponders, and 1 patient was a partial responder. Evaluation of the Y-BOCS, BDI, STAI- Trait, STAI-State, GAF, and EQ-5D showed statistically significant improvement at the last follow-up after GKRS. Neurological examinations were normal in all patients at each visit. At last follow-up, none of the patients had experienced any significant adverse neuropsychological effects or personality changes.

CONCLUSIONS GKRS anterior capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It reduces both obsessions and compulsions, improves quality of life, and diminishes depression and anxiety.

Arachnoiditis as an outcome factor for microvascular decompression in classical trigeminal neuralgia

Acta Neurochirurgica (2019) 161:1589–1598

Neurovascular conflict is considered a key element of classical trigeminal neuralgia (TN) and consequently, mi- crovascular decompression (MVD) is an effective treatment. Nevertheless, failures of MVD are described by many authors. In some patients, the arachnoid membranes surrounding the trigeminal nerve and neighbouring vessels may be thickened and adhesive. Here we analyse the impact of such focal arachnoiditis on outcome after MVD for TN.

Methods A cohort of prospectively followed patients after their MVD was reviewed for intraoperative, imaging and clinical data if findings of arachnoiditis during MVD were described. Long-term outcome assessment was the main endpoint.

Results We reviewed data from 395 MVD procedures, performed for TN from 2001 to 2014. Intraoperative evidence of focal arachnoiditis, as described by the surgeon, has been noted in 51 patients (13%). In 35 (68.6%), neuralgia was typical and in the other 17 (31.4%) it was atypical.
As expected by definition, neurovascular conflict was found in 49 interventions (96%); it was predominantly arterial in 27 (52.9%). Accompanying arachnoiditis was encountered: mild in 20 interventions (39.2%), severe in 31 (60.8%).
A successful result (BNI I or II) was achieved in 29 patients (56.9%). The other 22 patients (43.1%) had persistence or recurrence of pain. Overall KM probability of being pain free at 15 years was 72%.

Conclusions Intraoperative finding of arachnoiditis during MVD for classical trigeminal neuralgia is associated with poorer outcome than that of classical trigeminal neuralgia in general. This is particularly true for low grades of conflict.

Pain-free and pain-controlled survival after sectioning the nervus intermedius in nervus intermedius neuralgia: a single-institution review

J Neurosurg 131:352–359, 2019

Nervus intermedius neuralgia (NIN) or geniculate neuralgia is a rare facial pain condition consisting of sharp, lancinating pain deep in the ear and can occur alongside trigeminal neuralgia (TN). Studies on the clinical presentation, intraoperative findings, and ultimately postoperative outcomes are extremely limited. The aim of this study was to examine the clinical presentation and surgical findings, and determine pain-free survival after sectioning of the nervus intermedius (NI).

METHODS The authors conducted a retrospective chart review and survey of patients who were diagnosed with NIN at one institution and who underwent neurosurgical interventions. Pain-free survival was determined through chart review and phone interviews using a modified facial pain and quality of life questionnaire and represented as Kaplan-Meier curves.

RESULTS The authors found 15 patients with NIN who underwent microsurgical intervention performed by two sur- geons from 2002 to 2016 at a single institution. Fourteen of these patients underwent sectioning of the NI, and 8 of 14 had concomitant TN. Five patients had visible neurovascular compression (NVC) of the NI by the anterior inferior cerebellar artery in most cases where NVC was found. The most common postoperative complaints were dizziness and vertigo, diplopia, ear fullness, tinnitus, and temporary facial nerve palsy. Thirteen of the 14 patients reportedly experienced pain relief immediately after surgery. The mean length of follow-up was 6.41 years (range 8 months to 14.5 years). Overall recurrence of any pain was 42% (6 of 14), and 4 patients (isolated NIN that received NI sectioning alone) reported their pain was the same or worse than before surgery at longest follow-up. The median pain-free survival was 4.82 years ± 14.85 months. The median pain-controlled survival was 6.22 years ± 15.78 months.

CONCLUSIONS In this retrospective review, sectioning of the NI produced no major complications, such as permanent facial weakness or deafness, and was effective for patients when performed in addition to other procedures. After sectioning of the NI, patients experienced 4.8 years pain free and experienced 6.2 years of less pain than before surgery. Alone, sectioning of the NI was not effective. The pathophysiology of NIN is not entirely understood. It appears that neurovascular compression plays only a minor role in the syndrome and there is a high degree of overlap with TN.

Nervus intermedius and the surgical management of geniculate neuralgia

J Neurosurg 131:343–351, 2019

Geniculate neuralgia (GN) is an uncommon craniofacial pain syndrome attributable to nervus intermedius (NI) dysfunction. Diagnosis and treatment can be challenging, due to the complex nature of ear sensory innervation, resulting in clinical overlap with trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN).

METHODS A retrospective review of a prospective neurosurgical database at our institution was performed, 2000–2017, with a corresponding systematic literature review. Pain outcomes were dichotomized as unfavorable for unchanged/worsened symptoms versus favorable if improved/resolved. Eight formalin-fixed brains were examined to describe NI at the brainstem.

RESULTS Eleven patients were surgically treated for GN—9 primary, 2 reoperations. The median age was 48, 7 pa- tients were female, and the median follow-up was 11 months (range 3–143). Seven had ≥ 2 probable cranial neuralgias. NI was sectioned in 9 and treated via microvascular decompression (MVD) in 2. Five patients underwent simultaneous treatment for TN (4 MVD; 1 rhizotomy) and 5 for GPN (3 MVD; 2 rhizotomy). Eleven reported symptomatic improvement (100%); 8 initially reported complete resolution (73%). Pain outcomes at last contact were favorable in 8 (73%)—all among the 9 primary operations (89% vs 0%, p = 0.054). Six prior series reported outcomes in 111 patients.

CONCLUSIONS GN is rare, and diagnosis is confounded by symptomatic overlap with TN/GPN. Directed treatment of all possible neuralgias improved pain control in almost all primary operations. Repeat surgery seems a risk factor for an unfavorable outcome. NI is adherent to superomedial VIII at the brainstem; the intermediate/cisternal portion is optimal for visualization and sectioning.

Degradation of Neuronal Encoding of Speech in the Subthalamic Nucleus in Parkinson’s Disease

Neurosurgery 84:378–387, 2019

Most of the patients with Parkinson’s disease suffer from speech disorders characterized mainly by dysarthria and hypophonia.

OBJECTIVE: To understand the deterioration of speech in the course of Parkinson’s disease.

METHODS: We intraoperatively recorded single neuron activity in the subthalamic nucleus of 18 neurosurgical patients with Parkinson’s disease undergoing implantation of deep brain stimulator while patients articulated 5 vowel sounds.

RESULTS: Here, we report that single subthalamic neurons encode individual vowel phonemes and employ 1 of 2 encoding schemes: broad or sharp tuning. Broadly tuned units respond to all examined phonemes, each with a different firing rate, whereas sharply tuned ones are specific to 1 to 2 phonemes. We then show that in comparison with patients without speech deficits, the spiking activity in patients with speech disorders was lower during speech production, overt or imagined, but not during perception. However, patients with speech disorders employed a larger percentage of the neurons for the aforementioned tasks. Whereas the lower firing rates affect mainly sharply tuned units, the extra units used a broad tuning encoding scheme.

CONCLUSION: Our findings suggest mechanisms of neuronal degradation due to Parkinsonian speech disorders and their possible compensation. As impairment in sharply tuned units may be compensated by broadly tuned ones, the proposed compensation model appears to be suboptimal, lending support to the persistence of speech disorders in the course of the disease.

Effect of Bilateral Anterior Cingulotomy on Chronic Neuropathic Pain with Severe Depression

World Neurosurg. (2019) 121:196-200.

The presence of neuropathic pain can severely impinge on emotional regulation and activities of daily living including social activities, resulting in diminished life satisfaction. Unfortunately, the majority of patients with neuropathic pain do not experience an amelioration of symptoms from conventional therapies, even when multimodal therapies are used. Chronic refractory neuropathic pain is usually accompanied by severe depression that is prone to incur suicidal events; thus clinical management of chronic neuropathic pain and depression presents a serious challenge for clinicians and patients.

CASE DESCRIPTION: Two patients presented at our institution with neuropathic pain and severe depression. The patients had different pain symptoms emerging a few months after central or peripheral nervous system impairment. These symptoms were associated with the development of severe depression, social isolation, and a gradual inability to perform daily activities. Both patients were referred to our treatment center for bilateral anterior cingulotomy. After surgery, both patients showed significant progressive improvements in perceived pain, mental health status, and daily functioning. –

CONCLUSIONS: Bilateral anterior cingulotomy may serve as an alternative treatment for medically refractory neuropathic pain, especially for patients who also experience depression

The Impact of Diffusion Tensor Imaging Fiber Tracking of the Corticospinal Tract Based on Navigated Transcranial Magnetic Stimulation on Surgery of Motor-Eloquent Brain Lesions

Neurosurgery 83:768–782, 2018

Navigated transcranialmagnetic stimulation (nTMS) enables preoperative mapping of the motor cortex (M1). The combination of nTMSwith diffusion tensor imaging fiber tracking (DTI-FT) of the corticospinal tract (CST) has been described; however, its impact on surgery of motor-eloquent lesions has not been addressed.

OBJECTIVE: To analyze the impact of nTMS-basedmapping on surgery ofmotor-eloquent lesions.

METHODS: In this retrospective case-control study, we reviewed the data of patients operated for suspected motor-eloquent lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and, from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative risk/benefit analysis, surgical strategy, craniotomy size, extent of resection (EOR), and outcome were compared with a control group.

RESULTS: We included 35 patients who underwent nTMS mapping of M1 (group A), 35 patients who also underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of 35 patients treated without nTMS (group C). The patients in groups A and B received smaller craniotomies (P = .01; P = .001), had less postoperative seizures (P = .02), and a better postoperativemotor performance (P=.04) and Karnofsky Performance Status (P=.009) than the controls. Group B exhibited an improved risk/benefit analysis (P=.006), an increased EOR of nTMS-negative lesions in absence of preoperative motor deficits (P = .01), and less motor and Karnofsky Performance Status worsening in case of preoperative motor deficits (P = .02, P = .03) than group A.

CONCLUSION: nTMS-based mapping enables a tailored surgical approach for motor eloquent lesions. It may improve the risk/benefit analysis, EOR and outcome, particularly when nTMS-based DTI-FT is performed.

Deep brain stimulation for dementias

Neurosurg Focus 45 (2):E8, 2018

The aim of this article is to review the authors’ and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD).

METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events.

RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations.

CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson’s Disease

Neurosurgery 82:753–756, 2018

QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson’s disease, as measured by improvements in Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III) scores?

RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson’s disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I)

QUESTION 2: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson’s disease?

RECOMMENDATION: When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson’s disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I)

QUESTION 3: Is bilateral STN DBSmore, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson’s disease?

RECOMMENDATION: There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of “on” medication dyskinesias, the GPi should be targeted. (Level I)

QUESTION 4: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson’s disease?

RECOMMENDATION:When considering improvements in quality of life in a patient undergoing DBS for Parkinson’s disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I) QUESTION 5: Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease?

RECOMMENDATION: If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I)

QUESTION 6: Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson’s disease?

RECOMMENDATION: If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I)

QUESTION 7: Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson’s disease?

RECOMMENDATION: There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events.

The full guideline can be found at: https://www.cns.org/guidelines/deep-brainstimulation- parkinsons-disease.