Cerebellar Cortex Stimulation for Acquired Dystonia: A Case Report and Review of Its Role in Modern Surgical Practice.

BACKGROUND: Cerebral palsy (CP) is a common cause of acquired dystonia, which can lead to significant interference with quality of life and societal participation. In the last two decades, the surgical treatment of dystonia has primarily focused on deep brain stimulation targeting the basal ganglia and thalamic circuits. However, stimulation of the basal ganglia has generally been less effective in acquired combined forms of dystonia, including dystonic CP. These limitations, along with growing evidence for the role of the cerebellum in the pathophysiology of dystonia, have led to renewed interest in the cerebellum as a target for therapeutic stimulation in dystonia. Nevertheless, there are very few contemporary studies demonstrating its use. We present the case of a patient with generalized dystonia due to dyskinetic CP who was successfully treated with stimulation of the cerebellar cortex in the modern era. We also review the evidence underpinning targeting of the cerebellum in surgical therapy for dystonia and examine the latest reports of this approach in the surgical literature. SUMMARY: The patient derived significant improvement in the control of her dystonic symptoms, with a reduction in her BFMDRS score from 83 to 25. No complications were observed during more than 3 years of postoperative follow-up. Since the turn of the 21st century, there have been only 7 reports of cerebellar stimulation for dystonia, recruiting a total of 18 patients. These studies have exclusively targeted deep brain structures, making the present report of cortical cerebellar stimulation particularly unique. KEY MESSAGES: In the 21st century, cerebellar stimulation has predominantly been a second-line treatment for dystonia, after the failure of DBS targeting more mainstream loci within the thalamus and globus pallidus. However, there is increasing recognition of the role of the cerebellum in movement disorders, with multiple convergent lines of evidence supporting its involvement in dystonia pathophysiology. The cerebellum is worthy of greater consideration as a target for neurostimulation in dystonia, particularly in cases of acquired etiology.

Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis.

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes. METHODS: Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6 months were excluded. RESULTS: The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77-82] and 58% [50-66] at last follow-up. After primary TSS, predictors of remission were micro- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 µg/dL (< 55 nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmol v 1726 nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, p < 0.01). Recurrence rates after primary and revision TSS were 18% [14-22] and 28% [16-42]. CONCLUSIONS: TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L).

First treatment and retreatment of medically refractive trigeminal neuralgia by stereotactic radiosurgery versus microvascular decompression: a systematic review and Meta-analysis.

PURPOSE: Procedures to treat medically refractory trigeminal neuralgia (MRTN) include stereotactic radiosurgery (SRS) and microvascular decompression (MVD). The aim of this study was to compare outcomes of SRS versus MVD in the treatment of MRTN, with a subgroup focus on those being treated for the first time. METHODS: Search strategy was performed using the PRISMA guidelines for article identification, screening, eligibility and inclusion. Relevant articles were identified from six electronic databases from their inception to June 2017. These articles were screened against established criteria for inclusion into this study. Meta-analysis was conducted by pooling results with odds ratios and subgroup analysis. RESULTS: From 13 relevant studies identified, 683 patients treated by SRS were compared with 670 patients treated by MVD for MRTN. Overall, the significant findings were that compared to MVD, SRS was associated with lower rates of short-term (OR = 0.16; 95%CI = 0.11-0.22; p < .001) and long-term pain freedom (OR = 0.31; 95%CI = 0.22-0.44; p < .001), fewer postoperative complications (OR = 0.06; 95%CI = 0.02-0.16; p < .001), more facial numbness and dysesthesia (OR = 1.64; 95%CI = 1.08-2.49; p = .02), and more pain recurrence (OR = 2.28; 95%CI = 1.32-3.93; p = .003). These trends were all reflected in MRTN patients being treated for the first time. CONCLUSION: Both SRS and MVD alleviate pain in MRTN patients. MVD results in superior rates of short- and long-term pain relief, facial numbness and dysesthesia control, and less recurrence amongst those in whom pain freedom was achieved, at the cost of greater postoperative complications when compared to SRS. Although no significant difference was found in terms of the need for retreatment surgery, there was a trend towards less procedures favoring MVD. First treatment by either technique represents the overall trends reported.

Headache in Patients with Sellar Disease: Clinicomorphological Predictors of Headache and the Outcome of Endoscopic Transsphenoidal Surgery.

Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = -0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = -0.682, p < 0.001, MIDAS: R 2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.

Endoscopic Endonasal Biopsy for Diagnosis of Undifferentiated Lesions of the Cavernous Sinus.

BACKGROUND: Radiologically undifferentiated lesions of the cavernous sinus can pose a diagnostic challenge. Although radiotherapy is the mainstay for treatment of cavernous sinus lesions, histologic diagnosis allows access to a wide variety of alternative treatment modalities. The region is considered a high-risk area for open transcranial surgical access, and the endoscopic endonasal approach presents an alternative technique for biopsy. METHODS: A retrospective case series was performed of all patients undergoing endoscopic endonasal biopsy of isolated cavernous sinus lesions at 2 tertiary institutions. The primary outcomes were the percentage of patients in whom a histologic diagnosis was achieved and the proportion of patients in whom therapy differed from radiotherapy alone. Secondary outcomes included preoperative and postoperative 22-item Sino-Nasal Outcome Test symptom scores, as well as perioperative adverse outcomes. RESULTS: Eleven patients underwent endoscopic endonasal biopsy, with a diagnosis achieved in 10 patients. The most common diagnosis was perineural spread of squamous cell carcinoma, followed by perineuroma and single cases of metastatic melanoma, metastatic adenoid cystic carcinoma, mycobacterium lepri infection, neurofibroma, and lymphoma. Six patients had treatments other than radiotherapy, including immunotherapy, antibiotics, corticosteroids, chemotherapy, and observation alone. There was no significant difference in prebiopsy and postbiopsy 22-item Sino-Nasal Outcome Test scores. There was 1 case of epistaxis requiring return to theater for cautery of the sphenopalatine artery and there were no mortalities. CONCLUSIONS: In a limited case series, endoscopic endonasal biopsy was safe and effective in obtaining diagnosis for cavernous sinus lesions and had a significant impact on therapeutic decision making.

Low but not undetectable early postoperative nadir serum cortisol predicts sustained remission in Cushing's disease.

Objective: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease. The objectives of the study were to determine remission and recurrence rates after TSS for Cushing's disease, identify factors that predict these outcomes, and define the threshold for postoperative morning serum cortisol (MSeC) that most accurately predicts sustained remission. Methods: Records were retrospectively reviewed for consecutive adults undergoing TSS for Cushing's disease at a tertiary centre (1990-2019). Remission was defined as MSeC <138 nmol/L by 6 weeks postoperatively. Recurrence was defined as elevated 24-h urine free cortisol, lack of suppression after dexamethasone or elevated midnight salivary cortisol. Results: In this study, 42 patients (age 47 ± 13 years, 83% female) were assessed with 55 ± 56 months of follow-up. Remission occurred after 77% of primary (n = 30) and 42% of revision operations (n = 12). After primary surgery, remission was associated with lower MSeC nadir (26 ± 36 nmol/L vs 347 ± 220 nmol/L, P < 0.01) and lower adrenocorticotropin nadir (2 ± 3 pmol/L vs 6 ± 3 pmol/L, P = 0.01). Sustained remission 5 years after surgery was predicted by MSeC <92 nmol/L within 2 weeks postoperatively (sensitivity 100% and specificity 100%). After revision surgery, remission was predicted by lower MSeC nadir (70 ± 45 nmol/L vs 408 ± 305 nmol/L, P = 0.03), smaller tumour diameter (3 ± 2 mm vs 15 ± 13 mm, P = 0.05) and absence of cavernous sinus invasion (0% vs 71%, P = 0.03). Recurrence after primary and revision surgery occurred in 17% and 20% of patients respectively. Conclusions: Lower postoperative MSeC nadir strongly predicted remission after both primary and revision surgery. Following primary surgery, an MSeC <92 nmol/L within 2 weeks predicted sustained remission at 5 years. MSeC nadir was the most important prognostic marker following TSS for Cushing's disease.

Predictors of thermal response and lesion size in patients undergoing magnetic resonance-guided focused ultrasound thalamotomy.

Magnetic resonance-guided focused ultrasound (MRgFUS) is being increasingly utilized in the treatment of movement disorders such as essential tremor (ET) and Parkinson's disease (PD). Whilst skull density ratio (SDR) has previously been correlated with achieving lesional temperature rises, other patient factors such as brain and cerebrospinal fluid (CSF) volume have not previously been investigated. We aimed to investigate the effect of brain and CSF volumes on lesional temperature rises, as well as the effect of brain and CSF volumes and SDR on post-treatment lesion sizes. Fifty-four consecutive patients were studied with patient and treatment-related variables collected along with post-treatment lesion sizes. Linear regression analysis identified that SDR alone was associated with lesional temperatures. Both SDR and brain atrophy were associated with post-treatment lesion sizes on linear regression analysis. On multiple linear regression analysis SDR was significantly associated with post-treatment lesion size, and the association between brain atrophy and lesion sizes approached significance, a finding that warrants further investigation.

Assessment of magnetic resonance imaging criteria for the diagnosis of cavernous sinus invasion by pituitary tumors.

Cavernous sinus invasion (CSI) by pituitary tumors is associated with subtotal resection and persistent endocrinopathy. The Knosp classification is a magnetic resonance imaging (MRI) tool used to define CSI in the 2017 World Health Organization Classification. However, alternative criteria may have superior diagnostic performance. This study aimed to assess the diagnostic performance of four MRI criteria, using a combination of endoscopy and day 1 MRI as the reference standard for CSI. A cross-sectional study was conducted including patients treated with endoscopic endonasal transsphenoidal surgery for pituitary macroadenomas, recruited from a tertiary pituitary multidisciplinary center in Sydney, Australia between September 2013, and February 2021. The diagnostic performances of four MRI criteria were assessed: the Knosp criteria, percentage encasement of the internal carotid (PEICA), venous compartment obliteration (VCO), and the Fernandez-Miranda classification. Reference CSI was defined using a combination of intraoperative endoscopy and day 1 MRI. A total of 210 cavernous sinuses (105 patients), were analyzed, (51.7 ±â€¯16.3yrs, 43% female), of which 18% had CSI. CSI was best diagnosed by Knosp ≥ 2 (63% sensitivity and 89% specificity), PEICA ≥ 28% (84% sensitivity and 77% specificity) and VCO of ≥ 3 compartments (65% sensitivity and 89% specificity). CSI was unlikely if any of the following signs were present: Knosp < 1, PEICA < 28%, preservation of the medial or superior compartments or sparing of the superior Fernandez-Miranda compartment (negative predictive value 95%, 95%, 94%, 91% and 92% respectively). In conclusion, alternatives to the Knops criteria including PEICA and VCO can aid CSI diagnosis.

Smell Preservation following Unilateral Endoscopic Transnasal Approach to Resection of Olfactory Groove Meningioma: A Multi-institutional Experience.

Introduction Olfactory groove meningiomas (OGMs) are often associated with loss of smell following resection. Loss of smell has a measurable impact on quality of life. Smell preservation has been previously described in open approaches for early stage or unilateral OGMs. Evidence of smell preservation in endoscopic approaches is lacking. Design A multi-institutional retrospective review was performed on consecutive patients who underwent unilateral endoscopic endonasal resection of OGM. A gross total resection was achieved with preservation of the contralateral olfactory cleft and bulb. Olfactory function was assessed with a six-point olfactory symptom score and the Sniffin' Sticks 12-item smell identification test (SS-12). Contralateral olfactory bulb volume was measured on postoperative magnetic resonance imaging. Results Four patients (age 42.0 ± 7.5, 75% female) were assessed. Olfactory function was assessed at 21.8 ± 5.6 months following surgery. All patients reported some degree of smell preservation (75% described a slight/mild impairment in smell or better). Olfactory identification was preserved with an SS-12 score of 9 ± 1.4 (anosmia defined as ≤6). The olfactory bulb volume was calculated to be 47.4 ± 15.9 mm 3 (normal >40 mm 3 ). Conclusion Smell preservation is possible following unilateral endoscopic endonasal resection of carefully selected OGM.

A systematic review of outcome in intramedullary ependymoma and astrocytoma.

The objective was to determine the impact of surgical resection and adjuvant therapies on survival in intramedullary ependymoma and astrocytoma. Secondary goals were to determine predictors of survival in surgical patients including histological grading, age and gender. Searching of Medline, Embase and Clinicaltrials.gov databases were performed. Multivariate analyses were performed for overall survival (OS) and progression-free survival (PFS) through Monte Carlo methods and Maximum Likelihood Estimation. 57 articles detail results for 3022 patients. Meta-analysis revealed the following factors to have a statistically significant effect on OS. Patients undergoing gross-total resection (GTR) are 5.37 times more likely to survive than patients with lesser volumes of tumor resected (HR for OS 1.68, p < 0.01). High-grade tumors were associated with a 14 times risk of death over low-grade tumors (HR for OS 2.64, p < 0.01). Radiation increased the risk of mortality in low-grade tumors (HR for OS 5.20, p < 0.01), but decreased mortality in high-grade lesions (HR for OS 2.46, p < 0.01). Adult patients were more likely to die from disease compared with pediatric patients by a factor of 1.6 (HR for OS 0.47, p < 0.01). In PFS, radiotherapy was associated with a reduced time to recurrence (HR for PFS 1.90, p < 0.01). There was a male predominance of 58%. Gender did not influence survival. 79% of patients demonstrated stable or improved functional neurological outcomes six months post-operatively. Our data indicates GTR improves OS in all tumor grades. Radiation improves OS only in the presence of high-grade histology. Advancing age and high-grade histology are negative prognostic indicators.

Glossopharyngeal Neuralgia Treatment Outcomes After Nerve Section, Microvascular Decompression, or Stereotactic Radiosurgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Glossopharyngeal neuralgia (GPN) is a rare neuralgic pain syndrome amenable to neurosurgical treatments, including nerve section (NS), microvascular decompression (MVD), and stereotactic radiosurgery (SRS). However, thorough comparisons of the modalities have not been performed to date. The objective of the present study was to compare the pain and complication outcomes after these approaches to GPN. METHODS: Searches of 7 electronic databases from inception to June 2018 were conducted following the appropriate guidelines. The incidence rates (IRs) of short-term (≤3 months) and long-term (≥12 months) pain relief and complications were extracted and analyzed using a meta-analysis. Meta-regression was used to assess for heterogeneity. RESULTS: A total of 792 GPN cases managed by NS, MVD, or SRS were described by 6, 11, and 6 studies, reporting outcomes for 282 (36%), 446 (56%), and 67 (8%) cases. The short-term pain relief rate was highest after NS postoperatively (IR, 94%; 95% confidence interval [CI], 88%-98%) and lowest after SRS at 3 months postoperatively (IR, 80%; 95% CI, 68%-96%). The postoperative complication rate was greatest after MVD (IR, 26%; 95% CI, 16%-38%) and lowest after SRS (IR, 0%; 95% CI, 0%-4%). The long-term pain relief rate was greatest after NS (IR, 96%; 95% CI, 91%-99%) and lowest after SRS (IR, 82%; 95% CI, 67%-94%). Statistically significant differences between the approaches were found for each outcome. CONCLUSION: Neurosurgical treatment of GPN is frequently performed by 1 of 3 modalities with unique outcomes profiles. NS might provide the most favorable treatment response, with respect to short- and long-term pain relief and postoperative outcomes.

Baló's concentric sclerosis and tumefactive demyelination: a shared immunopathogenesis?

Baló's concentric sclerosis (BCS) and tumefactive demyelination (TD) are considered atypical forms of multiple sclerosis (MS). Baló lesions are characterized by concentric rings corresponding to alternating bands of demyelination and relatively preserved myelin (Hu and Lucchinetti, 2009). Tumefactive lesions are pseudotumoural demyelinating lesions of >2 cm and may have an open ring-enhancing magnetic resonance imaging appearance (Hu and Lucchinetti, 2009; Lucchinetti et al., 2008; Altintas et al., 2012). We present a patient who developed limb weakness and focal seizures secondary to a lesion radiologically and histopathologically consistent with BCS who, six months later, developed a tumefactive demyelinating lesion. This is the first description of BCS and TD occurring in the same patient and is particularly notable because of the lack of any other more typical demyelinating lesions on the MRIs. The nature of BCS and TD in relation to more typical multiple sclerosis is discussed.

Prospective study of neuropsychological and psychosocial outcome following surgical excision of intracerebral arteriovenous malformations.

In this prospective study the neuropsychological and psychosocial function of 64 patients undergoing surgical resection of cerebral arteriovenous malformations was examined prior to surgery (T1), one month post-surgery (T2) and one year post-surgery (T3). A mild but widespread cognitive decline was observed pre-operatively. There was a trend toward decreased neuropsychological function at T2. All neuropsychological tests showed a trend toward improvement at T3 compared with both pre-operative (generally not statistically significant) and early post-operative values (generally significant). Patients were assessed for change between testing times. At T2 patients were more likely to have deteriorated than improved, whereas at T3 the group which had altered from baseline were more likely to have improved than deteriorated. Deterioration in some verbal/language tasks was more common for left sided AVMs. Outcome did not differ significantly for patients presenting with haemorrhage. Psychosocial function was unchanged at late follow-up for the majority of patients.

Image fusion pitfalls for cranial radiosurgery.

Stereotactic radiosurgery requires imaging to define both the stereotactic space in which the treatment is delivered and the target itself. Image fusion is the process of using rotation and translation to bring a second image set into alignment with the first image set. This allows the potential concurrent use of multiple image sets to define the target and stereotactic space. While a single magnetic resonance imaging (MRI) sequence alone can be used for delineation of the target and fiducials, there may be significant advantages to using additional imaging sets including other MRI sequences, computed tomography (CT) scans, and advanced imaging sets such as catheter-based angiography, diffusor tension imaging-based fiber tracking and positon emission tomography in order to more accurately define the target and surrounding critical structures. Stereotactic space is usually defined by detection of fiducials on the stereotactic head frame or mask system. Unfortunately MRI sequences are susceptible to geometric distortion, whereas CT scans do not face this problem (although they have poorer resolution of the target in most cases). Thus image fusion can allow the definition of stereotactic space to proceed from the geometrically accurate CT images at the same time as using MRI to define the target. The use of image fusion is associated with risk of error introduced by inaccuracies of the fusion process, as well as workflow changes that if not properly accounted for can mislead the treating clinician. The purpose of this review is to describe the uses of image fusion in stereotactic radiosurgery as well as its potential pitfalls.