Changes in treatment of intracranial aneurysms during the last decade in a large European neurovascular center.

OBJECTIVE: Treatment modality for ruptured and unruptured intracranial aneurysms has shifted during the last two decades from microsurgical treatment towards endovascular treatment. We present how this transition happened in a large European neurovascular center. METHODS: We conducted a retrospective observational study consecutive patients treated for an unruptured or ruptured intracranial aneurysm at Helsinki University Hospital during 2012-2022. We used Poisson regression analysis to report age-adjusted treatment trends by aneurysm location and rupture status. RESULTS: A total of 2491 patients with intracranial aneurysms were treated (44% ruptured, 56% unruptured): 1421 (57%) surgically and 1070 (43%) endovascularly. A general trend towards fewer treated aneurysms was noted. The proportion of patients treated surgically decreased from 90% in 2012 to 20% in 2022. The age-adjusted decrease of surgical versus endovascular treatment was 6.9%/year for all aneurysms, 6.8% for ruptured aneurysms, and 6.8% for unruptured aneurysms. The decrease of surgical treatment was most evident in unruptured vertebrobasilar aneurysms (10.8%/year), unruptured communicating artery aneurysms (10.1%/year), ruptured communicating artery aneurysms (10.0%/year), and ruptured internal carotid aneurysms (9.0%/year). There was no change in treatment modality for middle cerebral artery aneurysms, of which 85% were still surgically treated in 2022. A trend towards an increasing size for treated ruptured aneurysms was found (p = 0.033). CONCLUSION: A significant shift of the treatment modality from surgical to endovascular treatment occurred for all aneurysm locations except for middle cerebral artery aneurysms. Whether this shift has affected long-term safety and patient outcomes should be assessed in the future.

Towards parsimonious generative modeling of RNA families.

Generative probabilistic models emerge as a new paradigm in data-driven, evolution-informed design of biomolecular sequences. This paper introduces a novel approach, called Edge Activation Direct Coupling Analysis (eaDCA), tailored to the characteristics of RNA sequences, with a strong emphasis on simplicity, efficiency, and interpretability. eaDCA explicitly constructs sparse coevolutionary models for RNA families, achieving performance levels comparable to more complex methods while utilizing a significantly lower number of parameters. Our approach demonstrates efficiency in generating artificial RNA sequences that closely resemble their natural counterparts in both statistical analyses and SHAPE-MaP experiments, and in predicting the effect of mutations. Notably, eaDCA provides a unique feature: estimating the number of potential functional sequences within a given RNA family. For example, in the case of cyclic di-AMP riboswitches (RF00379), our analysis suggests the existence of approximately 1039 functional nucleotide sequences. While huge compared to the known <4000 natural sequences, this number represents only a tiny fraction of the vast pool of nearly 1082 possible nucleotide sequences of the same length (136 nucleotides). These results underscore the promise of sparse and interpretable generative models, such as eaDCA, in enhancing our understanding of the expansive RNA sequence space.

Lateral-PLIF for spinal arthrodesis: concept, technique, results, complications, and outcomes.

BACKGROUND: Posterior lumbar interbody fusion (PLIF) surgery represents an effective option to treat degenerative conditions in the lumbar spine. To reduce the drawbacks of the classical technique, we developed a variant, so-called Lateral-PLIF, which we then evaluated through a prospective consecutive series of patients. METHODS: All adult patients treated at our institute with single or double level Lateral-PLIF for lumbar degenerative disease from January to December 2017 were prospectively collected. Exclusion criteria were patients < 18 years of age, traumatic patients, active infection, or malignancy, as well as unavailability of clinical and/or radiological follow-up data. The technique consists of insert the cages bilaterally through the transition zone between the central canal and the intervertebral foramen, just above the lateral recess. Pre- and postoperative (2 years) questionnaires and phone interviews (4 years) assessed pain and functional outcomes. Data related to the surgical procedure, postoperative complications, and radiological findings (1 year) were collected. RESULTS: One hundred four patients were selected for the final analysis. The median age was 58 years and primary symptoms were mechanical back pain (100, 96.1%) and/or radicular pain (73, 70.2%). We found a high fusion rate (95%). A statistically significant improvement in functional outcome was also noted (ODI p < 0.001, Roland-Morris score p < 0.001). Walking distance increased from 812 m ± 543 m to 3443 m ± 712 m (p < 0.001). Complications included dural tear (6.7%), infection/wound dehiscence (4.8%), and instrument failure (1.9%) but no neurological deterioration. CONCLUSIONS: Lateral-PLIF is a safe and effective technique for lumbar interbody fusion and may be considered for further comparative study validation with other techniques before extensive use to treat lumbar degenerative disease.

Even short-term training improves the skills of novice exoscope users: a prospective laboratory experiment.

BACKGROUND: The surgical 3D exoscopes have recently been introduced as an alternative to the surgical microscopes in microneurosurgery. Since the exoscope availability is still limited, it is relevant to know whether even a short-term exoscope training develops the skills needed for performing exoscope-assisted surgeries. METHODS: Ten participants (six consultants, four residents) performed two laboratory bypass test tasks with a 3D exoscope (Aesculap Aeos®). Six training sessions (6 h) were performed in between (interval of 2-5 weeks) on artificial models. The participants were divided into two groups: test group (n = 6) trained with the exoscope and control group (n = 4) with a surgical microscope. The test task was an artificial end-to-side microsurgical anastomosis model, using 12 interrupted 9-0 sutures and recorded on video. We compared the individual as well as group performance among the test subjects based on suturing time, anastomosis quality, and manual dexterity. RESULTS: Altogether, 20 bypass tasks were performed (baseline n = 10, follow-up n = 10). The median duration decreased by 28 min and 44% in the exoscope training group. The decrease was steeper (29 min, 45%) among the participants with less than 6 years of microneurosurgery experience compared to the more experienced participants (13 min, 24%). After training, the participants with at least 1-year experience of using the exoscope did not improve their task duration. The training with the exoscope led to a greater time reduction than the training with the microscope (44% vs 17%). CONCLUSIONS: Even short-term training with the exoscope led to marked improvements in exoscope-assisted bypass suturing among novice microneurosurgeons. For the more experienced participants, a plateau in the initial learning curve was reached quickly. A much longer-term effort might be needed to witness further improvement in this user group.

Digital exoscope versus surgical microscope in spinal dural arteriovenous fistula surgery: a comparative series.

OBJECTIVE: Surgical treatment of spinal dural arteriovenous fistulas (DAVFs) has been reported to be superior to endovascular treatment in terms of occlusion of the fistula. Despite the increased availability of digital 3D exoscopes, the potential benefits of using an exoscope in spinal DAVF surgery have not been studied. The purpose of this study was to report and compare the results of exoscope- and microscope-assisted surgery for spinal DAVFs. METHODS: All consecutive adult patients (≥ 18 years of age) treated surgically for spinal DAVFs from January 2016 to January 2023 in a tertiary neurosurgical referral center were included. All patients were operated on by one neurosurgeon. Their pre- and postoperative clinical findings, imaging studies, and intra- and postoperative events were evaluated and surgical videos from the operations were analyzed. RESULTS: Altogether, 14 patients received an operation for spinal DAVF during the study period, 10 (71%) with an exoscope and 4 (29%) with a microscope. The DAVFs were most commonly located in the lower parts of the thoracic spine in both groups. The duration of exoscopic surgeries was shorter (141 vs 151 minutes) and there was less blood loss (60 vs 100 ml) than with microscopic surgeries. No major surgical complications were observed in either group. Of the 14 patients, 10 had gait improvement postoperatively: 7 (78%) patients in the exoscope group and 3 (75%) in the microscope group. None of the patients experienced deterioration following surgery. CONCLUSIONS: Exoscope-assisted surgery for spinal DAVFs is comparable in safety and effectiveness to traditional microscopic surgery. With practice, experienced neurosurgeons can adapt to using the exoscope without major additional risks to the patient.

Digital 3D Exoscope is Safe and Effective in Surgery for Intradural Extramedullary Tumors: A Comparative Series.

BACKGROUND: Digital 3D exoscopes have been shown to be comparably safe and effective as surgical microscopes in complex microneurosurgical procedures. However, the results of exoscopic spinal tumor surgeries are scarce. The purpose of this study is to compare results of a transition from microscope to exoscope in surgeries for spinal intradural extramedullary tumors. METHODS: We included all consecutive patients with intradural extramedullary spinal tumors operated on by the senior author during January 2016 to October 2023. The 3D exoscope was used in the latter half of the series from November 2020. We evaluated pre- and postoperative clinical findings, imaging studies, intra- and postoperative events, and analyzed surgical videos from the operations retrospectively. RESULTS: We operated 35 patients (exoscope n = 19, microscope n = 16) for intradural extramedullary tumors (meningioma n = 18, schwannoma n = 12, other n = 5). Tumors in the cervical and thoracic spine were more common than in the lumbar region. The duration of surgery was slightly longer (median 220 vs. 185 minutes) in the exoscope group. However, the rate of gross total resection of the tumor was higher (81% vs. 67%) and the tumors more often located anteriorly to the spinal cord (42% vs. 13%) in the exoscope group. No major complications (i.e., permanent motor deficit or postoperative hematoma) occurred in either group. We saw postoperative gait improvement in 81% and 85% of the patients with preoperative deterioration of gait after exoscopic and microscopic surgeries, respectively. CONCLUSIONS: This study demonstrates that exoscope-assisted surgery for spinal intradural extramedullary tumors is comparable in safety and effectiveness to traditional microscopic surgery.

Hemangioblastoma and arteriovenous malformation in the same patient: a not random association or two isolated entities? Systematic review starting from a unique case.

BACKGROUND: The association between intracranial hemangioblastomas and arteriovenous malformations has been documented in very few cases in literature since 1965 and might present in three modalities: "intermixed, adjacent and separated (spatially and temporally)". Often, the pattern of presentation is "intermixed". According to our systematic review, we propose an adjustment of the previous classification, specifically for these entities. We describe the first case of a truly "spatially separated" association between these two lesions. METHODS: Our study encompassed all adult patients diagnosed with both intracranial hemangioblastoma and AVM who were evaluated in the last 20-year period, from 2003 to 2023 at Helsinki University Hospital. Cases of this coexistence were retrospectively identified and collected from clinical records. For the systematic review, studies reporting the coexistence of hemangioblastoma and AVM in adult patients (>18 years old) were selected. Given the rarity of this pattern, case reports were also included. RESULTS: The combined analysis of our systematic review and institutional retrospective study revealed a total of only seven identified cases. We applied the classification of neoplasms and AVM by Yano, modifying and adapting it into our screened patient series. We systematically reclassified "adjacent" and genuinely "spatially separated" patterns based on the vascular axis supplying both lesions. CONCLUSIONS: Hemangioblastomas and AVMs rarely coexist in the same patient. Our study reports the first instance of a truly "spatially separated" sporadic association between these vascular lesions. The rarity of such coexistence underscores the need for a nuanced and systematic classification to guide the management of these infrequent cases.

Exoscopic resection of giant olfactory groove meningioma.

Olfactory groove meningiomas represent 8%-13% of all intracranial meningiomas. Gross-total resection for large (4-6 cm) and giant (> 6 cm) cases remains challenging due to their relationship with critical neurovascular structures and extensive frontal lobe edema. A variety of transcranial and endoscopic approaches have been described. This 2D operative video shows the use of a digital 3D exoscope in the removal of a giant olfactory groove meningioma through a lateral supraorbital approach in a 57-year-old woman with visual impairment and apathy. The exoscope provides a very good angulated view of the subfrontal area on both sides of the anterior cranial fossa even through a small craniotomy. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23125.

Exoscopic extradural anterior clinoidectomy.

Extradural anterior clinoidectomy is a resourceful technique to decompress the optic nerve as well as increase exposure of the parasellar region during extensive approaches. Despite requiring adjunctive epidural bone work, this technique allows safe optic nerve mobilization and early devascularization for anterior clinoidal meningioma resection. This 2D operative video describes right optic nerve decompression by extradural anterior clinoidectomy and subsequent resection of a right Al-Mefty type III clinoid meningioma under exoscope magnification. The patient was a 50-year-old woman with a 1-year history of right visual acuity impairment and papillary atrophy. The exoscope allows a 360° view around the anterior clinoid, improving maneuverability. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23118.

Endonasal Endoscopic Optic Canal Decompression for Nontraumatic Optic Neuropathy: Long-Term Visual Outcomes in 36 Patients.

BACKGROUND: The management of compressive optic neuropathy (CON) arising from nontraumatic compression of the optic nerve within the optic canal (OC) remains a topic of controversy. In this study, our aim was to assess the effectiveness and safety of endonasal endoscopic optic nerve decompression (EEOND). In addition, we conducted an analysis of prognostic factors that could potentially influence visual outcomes. METHODS: This retrospective cohort study was conducted between January 2015 and December 2021, involving adult patients (age > 18) diagnosed with CON and treated with EEOND at our specialized skull base expert center. The study evaluated the impact of surgery on visual acuity (VA), mean deficit (MD), and foveal threshold (FT) of the visual field (VF). These parameters were assessed preoperatively and at 3- and 12-month postoperative follow-ups. The relationship between clinical variables and the differences in postoperative to preoperative VA, MD, and FT of the visual field was analyzed through univariate and multivariate approaches. RESULTS: Thirty-six patients (38 eyes) were included, with a mean age of 52 (±12) years, and a female predominance (78%). The mean ophthalmologic follow-up duration was 38 (±32) months. At the 12-month follow-up, 39% of the patients exhibited a VA improvement of ≥0.2 LogMAR. Partial VF improvement (MD improvement ≥25%) was observed in 55% of the patients, whereas 19% experienced complete recovery. In multivariate analysis, the presence of a type 4 OC was identified as the sole negative prognostic factor for visual improvement (VA and VF) at 12 months. Six patients (17%) encountered minor surgical complications, all of which were managed conservatively and had no impact on visual outcomes. CONCLUSIONS: Our study demonstrates that EEOND is a safe and effective procedure, even in cases of severe and long-lasting CON caused by nontraumatic compression of the optic nerve at the level of the OC.

First evidence of anti-VEGF efficacy in an adult case of adamantinomatous craniopharyngioma: Case report and illustrative review.

BACKGROUND: Craniopharyngioma (CP) is a neurosurgical challenge, due to location and to the substantial risk of morbidity associated with surgical resection. Recent advances in molecular research have identified a mutation signature in papillary craniopharyngiomas: BRAF V600E. This has led to targeted therapy, yielding positive results. Despite numerous studies of the pathophysiology of adamantinomatous craniopharyngioma, treatment options for molecular-based therapy are still lacking. The objective of our study was to provide an illustrative review of the literature on possible molecular targets in adamantinomatous craniopharyngioma and to report the case of a patient harboring an adamantinomatous craniopharyngioma deemed unsuitable for surgical resection, in which an anti-VEGF antibody was used to achieve tumor control. CASE REPORT: An 84-year-old-man was referred to our department with a history of visual loss caused by recurrent infundibular adamantinomatous craniopharyngioma. A first surgical attempt to reduce the cystic portion of the tumor compressing the optic pathway failed. Due to rapid worsening of visual function, adjuvant therapy with bevacizumab was initiated before radiotherapy. RESULTS: Neuroradiological and ophthalmological follow-up showed a decrease in tumor volume and improvement in visual function as early as 6 weeks after commencing therapy. These results were confirmed 3 months after commencement of chemotherapy. Radiotherapy was scheduled for long-term tumor control. CONCLUSIONS: To the best of our knowledge, our case is the first in the literature in which targeted therapy using anti-VEGF was successfully used as a single agent to treat adamantinomatous craniopharyngioma, with favorable outcome in terms of tumor shrinkage and clinical improvement. These preliminary results may open new perspectives for the management of adamantinomatous craniopharyngioma. Validation of this approach requires additional clinical evidence.

Frontal trans-sinusal approach: how I do it.

BACKGROUND: Anterior skull base lesions could be reached by different approaches (subfrontal, pterional, interhemispheric, etc.). In selected cases, the frontal trans-sinusal approach is an effective alternative to conventional techniques. METHODS: We present our technique to perform a frontal trans-sinusal approach in a patient affected by a large olfactory groove meningioma. DISCUSSION-CONCLUSION: The frontal trans-sinusal approach allows to approach safely lesions of the median anterior cranial fossa. This approach provides lower brain retraction, easier access to olfactory grooves, and earlier tumor devascularization. However, it remains limited to patients with large-sized frontal sinuses and entails some postoperative risks such as mucocele or CSF leak.

Brain Tumors Affecting the Orbit Globe and Orbit Tumors Affecting the Brain.

Brain tumors affecting the orbit and orbital tumors affecting the brain are a heterogeneous group of lesions, with histological features, behaviors, diagnostic criteria, and treatments varying from each other. Dermoid cyst and cavernous hemangiomas are considered the most frequent benign lesions, while non-Hodgkin lymphoma is the most common malignant tumor in this region. Sharing the same anatomical region, clinical manifestations of orbital lesions may be often common to different types of lesions. Imaging studies are useful in the differential diagnosis of orbital lesions and the planning of their management. Lesions can be classified into ocular or extra-ocular ones: the latter can be further differentiated into extraconal or intraconal, based on the relationship with the extraocular muscles. Surgical therapy is the treatment of choice for most orbital lesions; however, based on the degree of removal, their histology and extension, other treatments, such as chemotherapy and radiotherapy, are indicated for the management of orbital lesions. In selected cases, chemotherapy and radiotherapy are the primary treatments. This chapter aimed to discuss the orbital anatomy, the clinical manifestations, the clinical testing and the imaging studies for orbital lesions, and the principal pathological entities affecting the orbit together with the principles of orbital surgery.

Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature.

Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO classification of CNS tumors as two independent entities, due to different epidemiological, radiological, histopathological, and genetic patterns. With regard to papillary craniopharyngioma, a BRAF V600 mutation is detected in 95% of cases. This genetic feature is opening new frontiers in the treatment of these tumors using an adjuvant or, in selected cases, a neo-adjuvant approach. In this article, we present an overview of the more recent literature, focusing on the specificities and the role of oncological treatment in the management of papillary craniopharyngiomas. Based on our research and experience, we strongly suggest a multimodal approach combining clinical, endocrinological, radiological, histological, and oncological findings in both preoperative workup and postoperative follow up to define a roadmap integrating every aspect of this challenging condition.

MIS removal of extraforaminal lumbar spine schwannoma using MAS-TLIF retractor: technical note.

BACKGROUND: To report the use of Nuvasive MAS-TLIF retractor for the removal of lumbar spine schwannomas. METHODS: A 47-year-old man with 1-year history of back pain with progressive left sciatica underwent surgical resection of a left extraforaminal lumbar schwannoma (type IV according to Eden's classification) using the MAS-TLIF retractor. RESULTS: The patient completely recovered from the preoperative symptoms and was discharged three days after surgery. The MRI acquired 6 months postoperatively showed complete tumour removal, with no signs of instability. The MAS-TLIF retractor allows for an optimal paraspinal tissues retraction, improving the area of exposure and the manoeuverability angle. Moreover, the stability of the retraction is guaranteed by the positioning of the two transpedicular screws. Spinal fusion is not necessary because the posterior tension band is not jeopardised. CONCLUSIONS: MAS-TLIF retractor allows for a minimally invasive and safe surgical removal of LSS maximising surgical exposure and avoiding spinal fusion.

Neoadjuvant B-RAF and MEK Inhibitor Targeted Therapy for Adult Papillary Craniopharyngiomas: A New Treatment Paradigm.

Background: Surgical and clinical management of craniopharyngiomas is associated with high long-term morbidity especially in the case of hypothalamic involvement. Improvements in knowledge of craniopharyngioma molecular biology may offer the possibility of safe and effective medical neoadjuvant treatments in a subset of patients harboring papillary subtype tumors with a BRAFV600E mutation. Method: We report herein two cases of tubero-infundibular and ventricular Papillary Craniopharyngiomas in which BRAF/MEK inhibitor combined therapy was used as adjuvant (Case 1) or neoadjuvant (Case 2) treatment, with a 90% reduction in tumor volume observed after only 5 months. In Case 2 the only surgical procedure used was a minimal invasive biopsy by the trans-ventricular neuroendoscopic approach. As a consequence, targeted therapy was administered in purely neoadjuvant fashion. After shrinkage of the tumor, both patients underwent fractionated radiotherapy on the small tumor remnant to achieve long-term tumor control. A review of a previously reported case has also been performed. Result: This approach led to tumor control with minimal long-term morbidity in both cases. No side effects or complications were reported after medical treatment and adjuvant radiotherapy. Conclusion: Our experience and a review of the literature argue for a change in the current treatment paradigm for Craniopharyngiomas (CPs). In giant and invasive tumors, confirmation of BRAFV600E mutated PCPs by biopsy and BRAF/MEK inhibitor therapy before proposing other treatments may be useful to improve long term outcomes for patients.

Transcranial extradural subtemporal repair for sphenoid sinus lateral recess meningoencephalocele: technical note.

Cranial meningoencephalocele is a rare condition consisting of the herniation of meninges, CSF, and brain tissue through a cranial or skull base defect. Sphenoid sinus lateral recess meningoencephalocele is of particular interest due to the complex anatomy surrounding the bone defect and their demanding surgical management. In this technical note, we reported a step-by-step description of a rare case of sphenoid sinus lateral recess meningoencephalocele causing headache due to recurrent cerebrospinal fluid leak treated with a subtemporal craniotomy with extradural middle cranial fossa drilling and meningoencephalocele removal with multilayer reconstruction. The transcranial route is a safe and effective treatment for sphenoid sinus lateral recess meningoencephalocele repair. The subtemporal extradural approach allows for an optimal exposure of the relevant anatomy minimizing risks and improving the possibility to perform an effective multilayer skull base reconstruction.

Comparative Anatomical Study of Fronto-Orbito-Zygomatic and Fronto-Temporal Approach to the Central Skull Base.

ABSTRACT: Despite the advances in microsurgery and neuroanatomy, surgery of the central skull base still represents a challenge. Fronto-temporal approach has represented the mainstay of surgical approaches to this region. With advances in skull base surgery, orbital and zygomatic extensions were added to fronto-temporal approach to improve exposure minimizing brain retraction.The authors compared fronto-temporal and fronto-orbitozygomatic approaches to the central skull base by using the previously described operability score, to three different anatomical targets: the ipsilateral anterior clinoid process, the contralateral anterior clinoid process, and the ipsilateral posterior clinoid process.Based on the measurements taken, fronto-orbitozygomatic approache showed higher values at all 3 targets. The reported values were critically discussed.The operability score has been reported as an effective method to compare surgical approaches. The present study demonstrated the maximal possibility of exposure of the two approaches. Based on the strong variability of this anatomical region, especially because of the different pathologies, the authors suggest considering the operability score as a further tool to better define the best surgical approach to this anatomical region.

High γ-Aminobutyric Acid Content Within the Medial Prefrontal Cortex Is a Functional Signature of Somatic Symptoms Disorder in Patients With Parkinson's Disease.

BACKGROUND: The dysfunctional activity of the medial prefrontal cortex has been associated with the appearance of the somatic symptom disorder, a key feature of the Parkinson's disease (PD) psychosis complex. OBJECTIVES: The objectives of this study were to investigate whether the basal contents of inhibitory γ-aminobutyric acid and excitatory glutamate plus glutamine neurotransmitter levels are changed in the medial prefrontal cortex of patients with PD with somatic symptom disorder and whether this alteration represents a marker of susceptibility of PD to somatic symptom disorder, thus representing a signature of psychosis complex of PD. METHODS: Levels of the γ-aminobutyric acid and glutamate plus glutamine were investigated, at rest, with proton magnetic resonance spectroscopy. Total creatine was used as an internal reference. The study cohort included 23 patients with somatic symptom disorder plus PD, 19 patients with PD without somatic symptom disorder, 19 healthy control subjects, and 14 individuals with somatic symptom disorder who did not show other psychiatric or neurological disorders. RESULTS: We found that, compared with patients with PD without somatic symptom disorder or healthy control individuals, patients with somatic symptom disorder, with or without PD, show increased γ-aminobutyric acid/total creatine levels in the medial prefrontal cortex. The medial prefrontal cortex contents of glutamate plus glutamine/total creatine levels or γ-aminobutyric acid/glutamate plus glutamine were not different among groups. CONCLUSIONS: Our findings highlight a crucial pathophysiologic role played by high γ-aminobutyric acid within the medial prefrontal cortex in the production of somatic symptom disorder. This phenomenon represents a signature of psychosis complex in patients with PD. © 2020 International Parkinson and Movement Disorder Society.