KDM1A genotyping and expression in 146 sporadic somatotroph pituitary adenomas.

IMPORTANCE: A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism. OBJECTIVE: We aimed to analyze KDM1A gene sequence and KDM1A and GIPR expressions in somatotroph pituitary adenomas. SETTINGS: We conducted a cohort study at university hospitals in France and in Italy. We collected pituitary adenoma specimens from acromegalic patients who had undergone pituitary surgery. We performed targeted exome sequencing (gene panel analysis) and array-comparative genomic hybridization on somatic DNA derived from adenomas and performed droplet digital PCR on adenoma samples to quantify KDM1A and GIPR expressions. RESULTS: One hundred and forty-six patients with sporadic acromegaly were studied; 72.6% presented unsuppressed classical GH response, whereas 27.4% displayed a paradoxical rise in GH after oral glucose load. We did not identify any pathogenic variant in the KDM1A gene in the adenomas of these patients. However, we identified a recurrent 1p deletion encompassing the KDM1A locus in 29 adenomas and observed a higher prevalence of paradoxical GH rise (P = .0166), lower KDM1A expression (4.47 ± 2.49 vs 8.56 ± 5.62, P < .0001), and higher GIPR expression (1.09 ± 0.92 vs 0.43 ± 0.51, P = .0012) in adenomas from patients with KDM1A haploinsufficiency compared with those with 2 KDM1A copies. CONCLUSIONS AND RELEVANCE: Unlike in GIP-dependent primary bilateral macronodular adrenal hyperplasia, KDM1A genetic variations are not the cause of GIPR expression in somatotroph pituitary adenomas. Recurrent KDM1A haploinsufficiency, more frequently observed in GIPR-expressing adenomas, could be responsible for decreased KDM1A function resulting in transcriptional derepression on the GIPR locus.

Spinal Anterior Dural Dissection: Moving From Differential to Unifying Diagnosis.

BACKGROUND AND OBJECTIVES: Cerebrospinal fluid (CSF) collections extending longitudinally at the anterior aspect of the spinal dura have been reported in association with various conditions and under multiple names. The aim of this study was to report cases associated with brachial amyotrophy (BA) and examine its relationship with other clinical variants. METHODS: We conducted a retrospective cohort study including patients who presented with a motor deficit of the upper limbs and an anterior interdural CSF collection on spinal MRI. We performed a systematic review of the literature to include cases revealed by BA. RESULTS: Seven patients presenting with BA and a confirmed dural dissection on spinal MRI were included. All patients were male with a slowly progressing history of asymmetrical and proximal motor deficit of the upper limbs. Chronic denervation affecting mostly C5 and C6 roots was found on electroneuromyography. Spinal MRI demonstrated an anterior CSF collection dissecting the interdural space and exerting a traction on cervical motor roots. Dynamic computed tomography myelogram localized the dural defect every time it was performed (4/7 cases), and surgical closure was possible for 3 patients, leading to resolution of the collection. Literature review yielded 18 other published cases of spinal dural dissections revealed by BA, including 4 in association with spontaneous intracranial hypotension and 4 others in association with superficial siderosis. CONCLUSION: We propose a unifying diagnosis termed "spinal anterior dural dissection" (SADD) to encompass spinal dural CSF collections revealed by BA (SADD-BA), spontaneous intracranial hypotension (SADD-SIH), or superficial siderosis (SADD-SS).

Laminoplasty with tented duraplasty for Hirayama disease.

BACKGROUND: Hirayama disease (HD) is a characterized by progressive amyotrophy of the upper limbs due to a forward displacement of the cervical dura during neck flexion. METHODS: Unlike other treatment options aiming at preventing cervical flexion (e.g., collar or arthrodesis), laminoplasty with tented duraplasty addresses dural dysplasia. Technically, the procedure consists in enlarging the dural sac by performing an expansile duraplasty that is secured to the yellow ligaments, in association with an open-book laminoplasty. CONCLUSION: Laminoplasty with tented duraplasty is a surgical option addressing the cause of HD to prevent further neurological deterioration while preserving cervical motion.

Long-Term Outcomes after Incomplete Resection of Intramedullary Grade II Ependymomas: Is Adjuvant Radiotherapy Justified?

Ependymomas are the most common intramedullary tumors in adults. While gross total resection is the aim of surgery, tumor infiltration might limit resection. In cases of subtotal removal, the necessary adjuvant management remains unclear. The aim of our study was to assess the need for adjuvant radiotherapy after an incomplete resection of grade II intramedullary ependymomas (IME-II). We retrospectively reviewed all cases of IME-II operated upon at a single tertiary neurosurgical center from 2009 to 2018. Patients with anaplastic or myxopapillary ependymomas, and patients with a follow-up of less than three years, were excluded. We included 46 patients: 19 (41.3%) had a gross total resection; 21 (45.7%) had a subtotal resection; and 6 (13%) had a partial resection. None of the patients underwent adjuvant radiotherapy. Over a median follow-up of 79 months (range = 36-186), seven patients presented a radiological tumor progression with a mean delay of 50.9 months (range = 18-85), of which two were symptomatic (4.3%). Progression-free survival (PFS) was 90.1% at 5 years and 76.8% at 10 years. The extent of the resection was the only significant risk factor for secondary tumor progression (p = 0.012). Four of the seven patients with recurring IME-II were treated: three patients had a second surgery, leading to two GTR and one STR, followed by radiotherapy in one case, and one patient underwent radiotherapy alone. In this study, the rate of symptomatic progression and retreatment after incomplete resection of IME-II without adjuvant radiotherapy was low, suggesting a conservative approach in such cases.

Long-term outcome of surgical treatment for idiopathic spinal arachnoid web: A case series.

OBJECTIVE: Spinal arachnoid web (SAW) is a rare condition of the spine with limited long-term follow-up data in the literature. The longest reported follow-up period was an average 3.2 years. The objective of this study is to report our long-term results of patients who underwent surgical treatment for symptomatic idiopathic SAW. METHODS: We conducted a retrospective review of cases of idiopathic SAW that were operated between 2005-2020. We collected preoperative and last follow-up (LFU) data on motor force, sensory loss, pain, upper motor neuron (UMN) sign, gait disorder, sphincter dysfunction, syringomyelia, hyperintensity on T2-MRI, appearance of newer symptoms and number of reoperations. RESULTS: Our study included 9 patients with a mean follow-up period of 3.6years (range 2-9.1years). The surgical intervention involved a standard centered laminectomy, durotomy and arachnoid lysis. At presentation, motor weakness was present in 77.8% of patients, sensory loss in 66.7%, pain in 88.9%, sphincter dysfunction in 33.3%, UMN sign in 22%, gait disorder 55.6%, syringomyelia in 55.6% and MRI T2 hyperintensity in 55.6% of patients. At LFU, there was an improvement in all symptoms and signs to varying degrees. No new neurological symptoms appeared postoperatively, and there was no recurrence during the follow-up period. CONCLUSION: Our results demonstrate that the reported immediate and short-term favorable outcomes following arachnoid lysis for symptomatic SAW persist over a long-term period and the risk of readhesion-correlated neurological deterioration following conventional surgical intervention is low.

Bevacizumab in real-life patients with recurrent glioblastoma: benefit or futility?

PURPOSE: Angiogenesis plays a key role in glioblastoma, but most anti-angiogenic therapy trials have failed to change the poor outcome of this disease. Despite this, and because bevacizumab is known to alleviate symptoms, it is used in daily practice. We aimed to assess the real-life benefit in terms of overall survival, time to treatment failure, objective response, and clinical benefit in patients with recurrent glioblastoma treated with bevacizumab. METHODS: This was a monocentric, retrospective study including patients treated between 2006 and 2016 in our institution. RESULTS: 202 patients were included. The median duration of bevacizumab treatment was 6 months. Median time to treatment failure was 6.8 months (95%CI 5.3-8.2) and median overall survival was 23.7 months (95%CI 20.6-26.8). Fifty percent of patients had a radiological response at first MRI evaluation, and 56% experienced symptom amelioration. Grade 1/2 hypertension (n = 34, 17%) and grade one proteinuria (n = 20, 10%) were the most common side effects. CONCLUSIONS: This study reports a clinical benefit and an acceptable toxicity profile in patients with recurrent glioblastoma treated with bevacizumab. As the panel of therapies is still very limited for these tumors, this work supports the use of bevacizumab as a therapeutic option.

Surgical management of pituicytomas: a single-center case series.

OBJECTIVE: Pituicytomas (PT) are rare benign sellar and/or supra sellar tumors which surgical treatment might be challenging, owing to the hypervascularity of the tumor. Here, we report our experience with PTs, describe their clinical and radiological features, and propose an optimal therapeutic strategy. METHODS: This is a retrospective single-center study, reporting the clinical manifestations, radiological characteristics, histopathological features, treatment strategies and long-term outcomes of four patients who have been treated for a PT at Bicêtre University Hospital in Paris, France, over the past 7 years. RESULTS: Four patients were operated mean age at presentation was 60.25 years. Main symptoms, which tended to be progressive, included visual field defects and pituitary-hypothalamic dysfunction. Radiologically, all our cases resented with sellar and suprasellar localization with cavernous invasion in 75% of cases. Endoscopic transphenoidal approach was performed as first surgery for all cases. Transcranial route was done in one case. During surgery, important bleeding was observed in all cases. Gross total resection was obtained with a single surgery in two cases and a second surgery was necessary in the two remaining cases. Pathological diagnosis was confirmed in all cases. No recurrences were noted after an average follow-up of 3.6 years. CONCLUSIONS: PT is a rare differential diagnosis of sellar and/or parasellar tumors, whose hemorrhagic nature can become a challenge during surgery. We added four more cases to the literature to make physicians establish Piticytomas at suspicion diagnosis for sellar and/or suprasellar masses. Knowing the diagnosis, a preparation should be made preoperatively to avoid possible complications peroperatively.

Surgical Management after Chiari Decompression Failure: Craniovertebral Junction Revision versus Shunting Strategies.

Revision surgery after posterior fossa decompression for Chiari malformation is not uncommon and poses both strategic and technical challenges. We conducted a single-center retrospective cohort study including all adult patients who underwent revision surgery after posterior fossa decompression for Chiari type I malformation between 2010 and 2019. Among 311 consecutive patients operated on for Chiari malformation at our institution, 35 patients had a least one revision surgery with a mean follow-up of 70.2 months. Mean delay for revision was 28.8 months. First revision surgery was performed at the level of the foramen magnum in 25/35 cases and consisted in duraplasty revision in all cases, arachnolysis (51.4%), additional bone decompression (37.1%), tonsillar coagulation or resection (25.7%), 4th ventricle to cervical subarachnoid spaces shunt (5.7%). Most repeat revisions consisted in CSF diversion procedures, with either ventriculo-peritoneal or syringo-peritoneal shunts. Mean number of interventions per patient was 3.2, with 22.9% of patients undergoing 4 or more surgeries. Based on our experience, we propose that revision at the level of the foramen magnum should be considered as a first-line strategy for Chiari decompression failure. Shunting procedures can be performed in case of extensive arachnoiditis or repeated failures.

Spinal Solitary Fibrous Tumors: An Original Multicenter Series and Systematic Review of Presentation, Management, and Prognosis.

All solitary fibrous tumors (SFT), now histologically diagnosed by a positive nuclear STAT6 immunostaining, represent less than 2% of soft tissue sarcomas, with spinal SFT constituting a maximum of 2% of them, making these tumors extremely rare. We provide an up-to-date overview of their diagnosis, treatment, and prognosis. We included 10 primary STAT6-positive SFT from our retrospective cohort and 31 from a systematic review. Spinal pain was the most common symptom, in 69% of patients, and the only one in 34%, followed by spinal cord compression in 41%, radicular compression, including pain or deficit, in 36%, and urinary dysfunction specifically in 18%. Preoperative diagnosis was never obtained. Gross total resection was achieved in 71%, in the absence of spinal cord invasion or excessive bleeding. Histologically, they were 35% grade I, 25% grade II, and 40% grade III. Recurrence was observed in 43% after a mean 5.8 years (1 to 25). No significant risk factor was identified, but adjuvant radiotherapy improved the recurrence-free survival after subtotal resection. In conclusion, spinal SFT must be treated by neurosurgeons as part of a multidisciplinary team. Owing to their close relationship with the spinal cord, radiotherapy should be considered when gross total resection cannot be achieved, to lower the risk of recurrence.

Magendie's foramen debridement and catheterisation for the treatment of syringomyelia due to diffuse craniocervical junction arachnoiditis. A case report and technical note.

A 36 year old woman was referred to our department for symptomatic lumbar spinal arachnoiditis following an epidural anaesthesia for childbirth. She did not had other known causative factor and she was free of any neurological symptoms before. She rapidly developed lower limbs impairment by compressing intradural lumbar collections and arachnoiditis requiring surgical decompression and subsequently internal cerebrospinal fluid shunting for acute hydrocephalus. Three years and the half later, she developed a severe tetraparesis due to a massive syrinx consecutive to the fourth ventricle outlets obstruction cause by the ongoing diffuse craniocervical junction arachnoiditis. Our aim was to treat all the problems in one step. An open fourth ventriculostomy of the Magendie's foramen with catheter insertion from the fourth ventricle down to the upper cervical subarachnoid space improve both the patient status and imagery.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

Cognitive versus virtual reality simulation for evaluation of technical skills in neurosurgery.

OBJECTIVE: Simulation is gaining momentum as a new modality of medical training, particularly in acute care settings such as surgery. In the present study, the authors aimed to compare individual cognitive skills with manual abilities as assessed by virtual reality (VR) simulation among neurosurgical residents. METHODS: Participants were asked to complete a multiple-choice questionnaire assessing their surgical abilities regarding three basic neurosurgical procedures (endoscopic third ventriculostomy, cranial meningioma, and lumbar laminectomy). They subsequently performed these same three procedures on a VR simulator (NeuroTouch). RESULTS: The authors found that cognitive scores correlated with self-evaluation of surgical experience and autonomy. On the contrary, VR simulation, as assessed by NeuroTouch automated scoring, did not reflect participants' cognitive or self-evaluation of their surgical proficiency. CONCLUSIONS: The results of this study suggest that neurosurgical education should focus as much on cognitive simulation (e.g., careful planning and critical appraisal of actual procedures) as on VR training of visuomotor skills.

Outcome of pituitary hormone deficits after surgical treatment of nonfunctioning pituitary macroadenomas.

OBJECTIVES: Nonfunctionning pituitary macroadenomas (NFPMA) are benign tumors that cause symptoms of mass effects including hypopituitarism. Their primary treatment is transsphenoidal surgery. We aimed to determine the outcome of pituitary hormone deficits after surgical treatment of NFPMA and to identify factors predicting hormonal recovery. DESIGN: We retrospectively included 246 patients with NFPMA diagnosed and operated in one of the two participating centers. All hormonal axes were evaluated except growth hormone (GH). Postoperative improvement of pituitary endocrine function was considered if at least one hormonal deficit had recovered and a lower total number of deficits was observed 1 year after surgery. RESULTS: 80% (n = 197) of patients had one or more pituitary deficits and 28% had complete anterior hypopituitarism. Besides GH, the gonadotropic and thyrotropic axes were the most commonly affected (68% and 62%, respectively). The number of hypopituitary patients dropped significantly to 61% at 1 year (p < 0.001) and a significant improvement was observed for all hormonal axes, except central diabetes insipidus. Among patients with preoperative hypopituitarism, 88/175 (50%) showed improved pituitary function at 1 year. Both hyperprolactinemia at diagnosis and a lower tumor diameter independently predicted favorable endocrine outcome. CONCLUSIONS: Hypopituitarism is present in 80% of patients with NFPMA and nearly half of them will benefit from sustained improvement after surgery. Hyperprolactinaemia at diagnosis and lower tumor dimensions are associated with favorable endocrine prognosis. This supports the option of early surgery in NFPMA patients with pituitary deficits independent of the presence of visual disturbances.

Clinical characteristics and long-term surgical outcome of spinal myxopapillary ependymoma: a French cohort of 101 patients.

PURPOSE: Myxopapillary ependymoma (MPE) is the most frequent tumor affecting the medullary conus. The surgical therapeutic management is still debated and only few studies have focused on the postoperative clinical outcome of patients. This study aimed to demonstrate long-term postoperative outcome and to assess the predictive factors of recurrence as well as the clinical evolution of these patients. METHODS: From 1984 to 2019, in four French centers, 101 adult patients diagnosed with MPE were retrospectively included. RESULTS: Median age at surgery was 39 years. Median tumor size was 50 mm and lesions were multifocal in 13% of patients. All patients benefited from surgery and one patient received postoperative radiotherapy. Gross total resection was obtained in 75% of cases. Sixteen percent of patients presented recurrence after a median follow-up of 70 months. Progression free survival at 5 and 10 years were respectively estimated at 83% and 79%. After multivariable analysis, sacral localization, and subtotal resection were shown to be independently associated with tumor recurrence. 85% of the patients had a favorable evolution concerning pain. 12% of the patients presented a postoperative deterioration of sphincter function and 4% of motor function. CONCLUSION: Surgery alone is an acceptable option for MPE patients. Patients with sacral location or incomplete resection are at high risk of recurrence and should be carefully monitored.

Reintervention rate of arachnolysis versus shunting for nonforaminal syringomyelia.

OBJECTIVE: Surgical treatment for nonforaminal syringomyelia related to spinal arachnoiditis is still controversial. The authors sought to assess respective outcomes and rates of reintervention for shunting and spinal cord untethering (arachnolysis) in spinal arachnoiditis with syringomyelia. METHODS: This retrospective cohort study was conducted at a single reference center for syringomyelia. Patients undergoing arachnolysis and/or shunting interventions for nonforaminal syringomyelia were screened. RESULTS: The study included 75 patients undergoing 130 interventions. Arachnolysis without shunting was performed in 48 patients, while 27 patients underwent shunting. The mean follow-up between the first surgery and the last outpatient visit was 65.0 months (range 12-379 months, median 53 months). At the last follow-up, the modified McCormick score was improved or stabilized in 83.4% of patients after arachnolysis versus 66.7% after shunting. Thirty-one (41.3%) patients underwent reintervention during follow-up, with a mean delay of 33.2 months. The rate of reintervention was 29.2% in the arachnolysis group versus 63.0% in the shunting group (chi-square = 8.1, p = 0.007). However, this difference was largely driven by the extension of the arachnoiditis: in patients with focal arachnoiditis (≤ 2 spinal segments), the reintervention rate was 21.6% for arachnolysis versus 57.1% for shunting; in patients with extensive arachnoiditis, it was 54.5% versus 65.0%, respectively. Survival analysis assessing the time to the first reintervention demonstrated a better outcome in both the arachnolysis (p = 0.03) and the focal arachnoiditis (p = 0.04) groups. CONCLUSIONS: Arachnolysis led to fewer reinterventions than shunting in patients with nonforaminal syringomyelia. There was a high risk of reintervention for patients with extensive arachnopathies, irrespective of the surgical technique.