Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson's disease.

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy.

Effects of the COVID-19 Pandemic on Everyday Neurosurgical Practice in Alsace, France: Lessons Learned, Current Perspectives, and Future Challenges-Preliminary Results of a Longitudinal Multicentric Study Registry.

Background and Objectives: The global outbreak caused by the SARS-CoV-2 pandemic disrupted healthcare worldwide, impacting the organization of intensive care units and surgical care units. This study aimed to document the daily neurosurgical activity in Alsace, France, one of the European epicenters of the pandemic, and provide evidence of the adaptive strategies deployed during such a critical time for healthcare services. Materials and Methods: The multicentric longitudinal study was based on a prospective cohort of patients requiring neurosurgical care in the Neurosurgical Departments of Alsace, France, between March 2020 and March 2022. Surgical activity was compared with pre-pandemic performances through data obtained from electronic patient records. Results: A total of 3842 patients benefited from care in a neurosurgical unit during the period of interest; 2352 of them underwent surgeries with a wide range of pathologies treated. Surgeries were initially limited to neurosurgical emergencies only, then urgent cases were slowly reinstated; however, a significant drop in surgical volume and case mix was noticed during lockdown (March-May 2020). The crisis continued to impact surgical activity until March 2022; functional procedures were postponed, though some spine surgeries could progressively be performed starting in October 2021. Various social factors, such as increased alcohol consumption during the pandemic, influenced the severity of traumatic pathologies. The progressive return to the usual profile of surgical activity was characterized by a rebound of oncological interventions. Deferrable procedures for elective spinal and functional pathologies were the most affected, with unexpected medical and social impacts. Conclusions: The task shifting and task sharing approaches implemented during the first wave of the pandemic supported the reorganization of neurosurgical care in its aftermath and enabled the safe and timely execution of a broad spectrum of surgeries. Despite the substantial disruption to routine practices, marked by a significant reduction in elective surgical volumes, comprehensive records demonstrate the successful management of the full range of neurosurgical pathologies. This underscores the efficacy of adaptive strategies in navigating the challenges imposed by the largest healthcare crisis in recent history. Those lessons will continue to provide valuable insights and guidance for health and care managers to prepare for future unpredictable scenarios.

Endoscopic-enhanced supra-cerebellar trans-tentorial (SCTT) approach to temporo-mesial region: a multicenter study.

Surgical access to the temporo-mesial area may be achieved by several routes such as the sub-temporal, the temporal trans-ventricular, the pterional/trans-sylvian, and the occipital interhemispheric approaches; nonetheless, none of them has shown to be superior to the others. The supra-cerebellar trans-tentorial approach allows a great exposure of the middle and posterior temporo-mesial region, while avoiding temporal lobe retraction. A prospective multicenter study was designed to collect data on patients undergoing endoscopic-enhanced SCTT approach to excise left temporo-mesial lesions. The study involved 5 different neurosurgical European centers and ran from 2015 to 2020. All patients had preoperative as well as postoperative brain MRI and ophthalmology evaluation. A total of 30 patients were included in this study, the mean follow-up was 44 months (range 18 to 84 months), male/female ratio was 16/14, and mean age was 39 years. A gross total resection was achieved in 29/30 (96.7%) cases. All surgical procedures were uneventful, without transient or permanent neurological deficits thanks to the preservation of the posterior cerebral artery. The endoscopic-enhanced SCTT approach provides satisfactory exposure to the left temporo-mesial region. Its minimally invasive nature helps minimize the surgical risks related to vascular and white tract manipulation, which represent known limitations of open microsurgical as well as other approaches.

Impact of Subthalamic Deep Brain Stimulation on Impulse Control Disorders in Parkinson's Disease: A Prospective Study.

BACKGROUND: Impact of subthalamic deep brain stimulation (DBS) on impulse control disorders (ICD) in Parkinson's disease (PD) remains controversial. OBJECTIVES: The objectives of this study were to analyze the natural history of ICD between baseline and 1 year after subthalamic DBS in patients with PD and to identify predictive factors, taking into account the positions of the active contact and stimulation parameters. METHODS: We analyzed postoperative modifications of ICD based on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. ICD status and Ardouin Scale of Behaviour in PD were assessed at baseline and 1 year following subthalamic DBS. Location of active contacts within the 3 subthalamic nucleus functional territories was investigated. RESULTS: A total of 217 were patients included. Of the patients, 10.6% had ICD at baseline of which 95.6% improved at 1 year following subthalamic DBS; 3.6% of the patients experienced de novo ICD at 1 year following subthalamic DBS. Dopamine agonist dose reduction (from 309.8 to 109.3 mg) was the main driver of ICD regression (P = 0.05). Higher preoperative dyskinesias were associated with poorer ICD evolution (P = 0.04). Whereas baseline apathy was a risk factor of de novo ICD (P = 0.02), ICD improvement correlated with postoperative apathy (P = 0.004). Stimulation power and position of active contacts-mainly located within the sensorimotor part of the subthalamic nucleus-did not influence ICD. CONCLUSIONS: This 1-year, postoperative follow-up study showed ICD regression and dopaminergic drug reduction with optimal position of the active contacts within the subthalamic nucleus. Whereas patients with PD with preoperative ICD were prone to postoperative apathy, we also showed that those with preoperative apathy had a higher risk to experience postoperative de novo ICD, further highlighting the meaningful influence of postoperative management of dopaminergic medication on outcome and the continuum between apathy and ICD. © 2020 International Parkinson and Movement Disorder Society.

Anatomical characterisation of three different psychosurgical targets in the subthalamic area: from the basal ganglia to the limbic system.

Effective neural stimulation for the treatment of severe psychiatric disorders needs accurate characterisation of surgical targets. This is especially true for the medial subthalamic region (MSR) which contains three targets: the anteromedial STN for obsessive compulsive disorder (OCD), the medial forebrain bundle (MFB) for depression and OCD, and the "Sano triangle" for pathological aggressiveness. Blocks containing the subthalamic area were obtained from two human brains. After obtaining 11.7-Tesla MRI, blocks were cut in regular sections for immunohistochemistry. Fluorescent in situ hybridisation was performed on the macaque MSR. Electron microscopic observation for synaptic specialisation was performed on human and macaque subthalamic fresh samples. Images of human brain sections were reconstructed in a cryoblock which was registered on the MRI and histological slices were then registered. The STN contains glutamatergic and fewer GABAergic neurons and has no strict boundary with the adjacent MSR. The anteromedial STN has abundant dopaminergic and serotoninergic innervation with very sparse dopaminergic neurons. The MFB is composed of dense anterior dopaminergic and posterior serotoninergic fibres, and fewer cholinergic and glutamatergic fibres. Medially, the Sano triangle presumably contains orexinergic terminals from the hypothalamus, and neurons with strong nuclear oestrogen receptor-alpha staining with a decreased anteroposterior and mediolateral gradient of staining. These findings provide new insight regarding MSR cells and their fibre specialisation, forming a transition zone between the basal ganglia and the limbic systems. Our 3D reconstruction enabled us to visualize the main histological features of the three targets which should enable better targeting and understanding of neuromodulatory stimulation results in severe psychiatric conditions.

Delayed Intracerebral Hematoma after Ventriculoperitoneal Shunt in the Context of Ruptured Brain Arteriovenous Malformation: A Literature Review.

Hemorrhagic complications arising from ventricular drainage procedures are typically asymptomatic and of low volume. A particular subset of these complications, known as delayed intracranial hemorrhage (DICH), is however recognized for its particularly poor prognosis. We primarily aimed to identify epidemiological characteristics associated with DICH, to shed light on its occurrence and potential risk factors. To do so, we performed a retrospective analysis of a series of ten patients who presented with DICH in the context of a ruptured brain arteriovenous malformation (bAVM) and a systematic literature review of all DICH cases reported in the literature. Our ten patients showed delayed neurological deterioration after a ventriculoperitoneal shunt (VPS) procedure, with a computed tomography (CT) scan revealing a DICH surrounding the ventricular catheter, distinct and away from the nidus of their previously ruptured bAVM. Four patients (40%) rapidly declined and passed away, three (30%) required surgical management and the remaining three (30%) demonstrated gradual clinical improvement with conservative management. In the literature, most patients presenting with DICH had hydrocephalus associated with neurovascular disorders (47% of cases), such as bAVM rupture in our present series. These constatations point out the significance of the underlying pathologies potentially being predisposed to these unusual complications.

The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice.

While depression and chronic pain are frequently comorbid, underlying neuronal circuits and their psychopathological relevance remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. Moreover, activation of this pathway in naive male mice, in the absence of on-going pain, is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, which was significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of emotional dysfunction. Overall, these results place the amygdalo-cingulate pathway at the core of pain and depression comorbidity, and unravel the role of Sema4a and impaired myelination in mood control.

Pushing the boundaries of accuracy and reliability during stereotactic procedures: A prospective study on 526 biopsies comparing the frameless robotic and Image-Guided Surgery systems.

INTRODUCTION: A 12-year long, prospective, single center study was conducted, comparing two frameless systems for brain biopsies: ROSA robotic-assisted stereotaxy and BrainLab Varioguide image-guided stereotaxy (Image Guided Surgery, IGS). METHOD: All consecutive adult and pediatric patients undergoing frameless brain biopsies were included. Successfully achieving diagnosis was the primary endpoint, analysis of all periprocedural complications was the secondary endpoint, and the tertiary endpoint was the length of the procedure, with the aim of assessing of the learning curve for each operator over time. The results for the ROSA robot and the Varioguide system were compared and benchmarked to data from the literature. RESULTS: We performed 526 on 516 patients, 314 with the ROSA robot (Group A) and 212 with the IGS Varioguide (Group B). Histological diagnosis was achieved in 97.4% of cases in Group A, versus 93.3% in Group B (p < 0.05). No statistically significant difference was found for secondary and tertiary endpoints. The complication rate appeared similar between the 2 frameless systems, with a hemorrhagic complications rate of 3.5% in Group A and 4.7% in Group B. Permanent neurological deterioration was only recorded in 0.8% of cases from Group B. Mortality was recorded in 0.3% in Group A and 0.4% in Group B. CONCLUSION: This study provides evidence to confirm that robotic surgery lives up to its promises of increased safety, accuracy, and reliability.

Language and verbal fluency outcome after bilateral subthalamic Nucleus Deep Brain Stimulation in Parkinson's disease.

BACKGROUND: Language disorders in Parkinson's Disease (PD) following bilateral subthalamic Nucleus Deep Brain Stimulation (STN-DBS) are common. OBJECTIVE: To assess STN-DBS impact on language and observe clinical and anatomical predictors of poor outcome. METHODS: We prospectively included PD patients undergoing STN-DBS. We performed a neuropsychological evaluation focusing on language before (V0), 3 days after (V1), and 3 months after (V2) surgery. Patients performed all assessments in ON drug condition, V1 with the stimulation turned OFF to evaluate the lesion effect, and V2 with the stimulation turned ON to evaluate the stimulation effect. Electrodes and active contact locations were determined with MRI-Atlas fusion. The stimulation parameters and the total electrical energy delivered (TEED) were recorded for each patient. RESULTS: 18 PD patients consecutively operated were included. We identified a decline in phonemic verbal fluency (VFP) at V1 and V2 (p = 0.023 and 0.032 respectively), as well as in semantic verbal fluency (VFS) (p = 0.025 and 0.019, respectively). There was a significant slowdown in the verbs naming test (p = 0.048). No other language alteration was recorded. There was no correlation between demographic or clinical factors and verbal fluency (VF) evolution. Active contact location within substantia nigra was associated with VFP worsening (p = 0.047), while elevated TEED on the left-sided electrode was associated with VFS decline (p = 0.021). CONCLUSION: VF was significantly altered following STN-DBS. Location outside the dorsolateral sensorimotor STN, and high stimulation power appeared to promote this decline. Other language domains remained stable.

Freezing of gait depends on cortico-subthalamic network recruitment following STN-DBS in PD patients.

INTRODUCTION: Subthalamic deep-brain-stimulation (STN-DBS) is an effective means to treat Parkinson's disease (PD) symptoms. Its benefit on gait disorders is variable, with freezing of gait (FOG) worsening in about 30% of cases. Here, we investigate the clinical and anatomical features that could explain post-operative FOG. METHODS: Gait and balance disorders were assessed in 19 patients, before and after STN-DBS using clinical scales and gait recordings. The location of active stimulation contacts were evaluated individually and the volumes of activated tissue (VAT) modelled for each hemisphere. We used a whole brain tractography template constructed from another PD cohort to assess the connectivity of each VAT within the 39 Brodmann cortical areas (BA) to search for correlations between postoperative PD disability and cortico-subthalamic connectivity. RESULTS: STN-DBS induced a 100% improvement to a 166% worsening in gait disorders, with a mean FOG decrease of 36%. We found two large cortical clusters for VAT connectivity: one "prefrontal", mainly connected with BA 8,9,10,11 and 32, and one "sensorimotor", mainly connected with BA 1-2-3,4 and 6. After surgery, FOG severity positively correlated with the right prefrontal VAT connectivity, and negatively with the right sensorimotor VAT connectivity. The right prefrontal VAT connectivity also tended to be positively correlated with the UPDRS-III score, and negatively with step length. The MDRS score positively correlated with the right sensorimotor VAT connectivity. CONCLUSION: Recruiting right sensorimotor and avoiding right prefrontal cortico-subthalamic fibres with STN-DBS could explain reduced post-operative FOG, since gait is a complex locomotor program that necessitates accurate cognitive control.

Endoscopic Transorbital Approaches to Anterior and Middle Cranial Fossa: Exploring the Potentialities of a Modified Lateral Retrocanthal Approach.

BACKGROUND: Among the new perspectives to revolutionize skull base surgery, there are the transorbital neuroendoscopic (TONES) approaches to reach the anterior and middle cranial fossa (ACF and MCF). We conceived to explore the potentialities of a modified superiorly and medially extended lateral retrocanthal (LRC) approach. METHODS: Six head specimens were dissected. Applying the established conic model and the key surgical landmark of sphenofrontal suture, we tested the feasibility of a modified LRC to reach ACF and MCF; computed tomography (CT) scans were performed before and after dissection to obtain a morphometric analysis of the surgical corridors using a polygonal surfaces model. RESULTS: Through our anatomical study, we were able to identify and explore 3 different surgical corridors to reach the ACF and MCF: the superomedial, the superolateral, and the inferolateral. The superomedial corridor appeared most suitable to reach the medial part of the ACF and the optic-carotid region, whereas through the superolateral and inferolateral corridors it was possible to reach and explore the lateral part of ACF and MCF. The mean volumes of the 3 surgical corridors calculated on post-dissection CT scans were: 12.72 ± 1.99, 5.69 ± 0.34, and 6.24 ± 0.47 cm3, respectively. CONCLUSIONS: The development of TONES approaches has not replaced the traditional open or endoscopic approach; nonetheless, identification of surgical corridors and the possibility to combine them represent a major breakthrough. Clinical studies are necessary to demonstrate their validity and test the effectiveness, safety, and reproducibility of TONES approaches in managing lesions harboring in the ACF and MCF.

Primary Brain Rhabdomyosarcoma Causing Extracranial Metastases: Case Report with Narrative Review of Atypical Presentations and Their Diagnostic Challenges.

BACKGROUND: Rhabdomyosarcoma is a rare malignant tumor originating from striated muscle cells. It accounts for only 3% of all soft tissue sarcomas in adults, and its metastases can also reach the central nervous system. Only sporadic cases of primary brain rhabdomyosarcoma (PBRMS) have been reported so far. CASE DESCRIPTION: We discuss the atypical presentation and diagnostic challenge of PBRMS in a 65-year-old man. He presented with a 3-day history of progressive right hemiparesis caused by an unspecific left frontoparietal heterogeneously enhancing lesion. Total body computed tomography and positron emission tomography scans performed at baseline did not reveal other secondarisms. The patient underwent radical excision of the lesion, which allowed to establish the diagnosis, with immunohistochemical staining positive for desmin and myogenin. Stereotactic radiotherapy guaranteed local disease control; nonetheless, the patient also required adjuvant chemotherapy when he developed large right lung metastases 6 months postoperatively. CONCLUSIONS: PBRMS can be hardly distinguished from other malignant brain tumors during preoperative radiologic workup; only histology can raise the suspicion of primary or metastatic rhabdomyosarcoma, depending on the presence of other distant lesions. Our review of the literature demonstrates that prognosis is poor: 44% of patients die within 1 year from diagnosis. Overall, survival seems to correlate with radical resection, tolerance of stereotactic or if necessary full neuraxis radiotherapy, and adjuvant chemotherapy. Given the high relapse rate, close monitoring and restaging are imperative.

Cranioplasty with Porous Hydroxyapatite Custom-Made Bone Flap: Results from a Multicenter Study Enrolling 149 Patients Over 15 Years.

BACKGROUND: Despite the mixed evidence regarding the effect of decompressive craniectomy in terms of outcome, a tremendous increase in related reports has been observed in the last years. Cranioplasty plays a key role in restoring function and anatomy of the cranial vault. Considering that cranioplasty is not exempt from risks, the identification of the safest technique becomes crucial to achieve better patients' recovery. Porous hydroxyapatite (PHA) has received growing attention for its potential in bony integration. Here we report a multicenter prospective follow-up analysis of 149 patients who underwent cranioplasty with PHA prostheses. In particular, we focus on the incidence of adverse events and implant removal. METHOD: From January 2001 to December 2015 we conducted a prospective multicenter study of 149 patients who underwent cranioplasty with custom-made PHA flaps after decompressive craniectomy for several reasons. The endpoints were the incidence of adverse events after cranioplasty and of related implant removal. RESULTS: 66 patients (44%) were treated within 6 months from decompression, and only 2 patients had a bifrontal bilateral reconstruction. Of those, 25 patients reported complications (16.8%), and 9 of them (6% of the whole case series) required removal of the prosthesis. The only significant factor predicting cranioplasty removal was a previous infection. CONCLUSION: Hydroxyapatite for cranial implants is fully comparable to other heterologous materials. It has a biologic potential of bony integration. The risk of explants seems to be significantly higher in second-line patients, data not shown in previous studies.