Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes.

AIM: Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. METHODS: Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. RESULTS: Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. CONCLUSION: The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).

Aerosolisation in endonasal endoscopic pituitary surgery.

PURPOSE: To determine the particle size, concentration, airborne duration and spread during endoscopic endonasal pituitary surgery in actual patients in a theatre setting. METHODS: This observational study recruited a convenience sample of three patients. Procedures were performed in a positive pressure operating room. Particle image velocimetry and spectrometry with air sampling were used for aerosol detection. RESULTS: Intubation and extubation generated small particles (< 5 µm) in mean concentrations 12 times greater than background noise (p < 0.001). The mean particle concentrations during endonasal access were 4.5 times greater than background (p = 0.01). Particles were typically large (> 75 µm), remained airborne for up to 10 s and travelled up to 1.1 m. Use of a microdebrider generated mean aerosol concentrations 18 times above baseline (p = 0.005). High-speed drilling did not produce aerosols greater than baseline. Pituitary tumour resection generated mean aerosol concentrations less than background (p = 0.18). Surgical drape removal generated small and large particles in mean concentrations 6.4 times greater than background (p < 0.001). CONCLUSION: Intubation and extubation generate large amounts of small particles that remain suspended in air for long durations and disperse through theatre. Endonasal access and pituitary tumour resection generate smaller concentrations of larger particles which are airborne for shorter periods and travel shorter distances.

Younger age is a risk factor for regrowth and recurrence of nonfunctioning pituitary macroadenomas: Results from a single Australian centre.

OBJECTIVE: The natural history of nonfunctioning pituitary macroadenomas (NFPMA) after surgical resection is variable, with guidelines unable to define the duration of radiological follow-up. In this first Australian series, we identify risk factors for regrowth/recurrence of NFPMA to assist with guiding recommendations for long-term follow-up. DESIGN: Retrospective analysis of all radiotherapy-naïve cases with NFPMA resected between 1995 and 2013. PATIENTS: One hundred and twenty-three cases had both ≥2 postoperative scans and ≥12-month follow-up. MEASUREMENTS: Regrowth was defined as any sustained increase in diameter of residual adenoma or recurrence as any new adenoma occurring post complete resection on serial pituitary MRI. RESULTS: Median follow-up time was 48 months (interquartile range [IQR]: 31-86). Overall regrowth/recurrence occurred in 29% (36/123). Regrowth occurred in 40% (30/76) at a median time of 44.5 months (IQR 22-80) compared to recurrence of 12.5% (6/48; P=.003), occurring at a median time of 48 months (IQR 12-96; P=.7). Further treatment was required in 66.7% and 56.7%, respectively (=1.0). Risk factors for regrowth/recurrence by multivariate analysis were presence of residual disease and younger age at presentation. The longest time for regrowth was 168 months (14 years) and recurrence 156 months (13 years). CONCLUSIONS: Presence of postoperative residual adenoma and younger age at presentation are the main predictors of regrowth/recurrence in NFPMA. Long-term serial imaging is required to detect regrowth and recurrence in younger patients and those with residual disease. Most regrowth/recurrences will occur within 10 years of follow-up.

A Possible Role for Temporary Lumbar Drainage in the Management of Idiopathic Intracranial Hypertension.

This paper reports 14 patients with idiopathic intracranial hypertension (IIH) who experienced immediate and sustained resolution of their IIH; 13 in the setting of a low-pressure headache and 1 who underwent lumbar drainage for 4 days draining the cerebrospinal fluid (CSF) at a rate of 5-15 mL/h. These observations, if confirmed, suggest that draining CSF using a temporary lumbar drain draining CSF at a rate greater than it is produced may potentially have a pivotal role in the management of IIH.

Gender differences in presentation and outcome of nonfunctioning pituitary macroadenomas.

OBJECTIVES: Few data exist regarding gender differences in hormonal outcomes in nonfunctioning pituitary macroadenomas (NFPMA). The aim was to assess whether there are gender differences in hormonal outcomes in NFPMA following pituitary surgery at a single centre. DESIGN AND METHODS: Retrospective review of cases undergoing a first surgical procedure for NFPMA. Preoperative hormonal function was available for 122 cases at presentation and 94 cases 6 months postoperatively. Multiple hormone deficiency was defined as ≥2 hormonal axis losses. Tumour size and invasion on MRI scan were assessed independently by a single neuroradiologist. RESULTS: At presentation, men were more likely than women to have multiple hormonal deficiency (47% vs 28%, P = 0·038). Premenopausal women tended to have smaller adenomas than men, but neither adenoma size nor invasion was associated with multiple hormonal deficiency at presentation. Postoperatively, differences were observed with only 14% of premenopausal women exhibiting multiple hormone deficiency, compared with 36% of postmenopausal women and 46% of men (P = 0·03). Overall, postoperative hormonal recovery was observed in over one-third of cases. Greatest recovery occurred in the gonadal axis of 60% (6/10) premenopausal women compared with 19% (8/43) of other groups combined (P = 0·007). CONCLUSIONS: Premenopausal women with NFPMA appear to have favourable hormonal outcomes. This may be due to a complex interplay between smaller tumour size and shorter disease duration. There should be no hesitation in offering pituitary surgery to premenopausal women with NFPMA, who have the most to gain in terms of restoration of hormonal function.

Slim electrodes for improved targeting in deep brain stimulation.

OBJECTIVE: The efficacy of deep brain stimulation can be limited by factors including poor selectivity of stimulation, targeting error, and complications related to implant reliability and stability. We aimed to improve surgical outcomes by evaluating electrode leads with smaller diameter electrode and microelectrodes incorporated which can be used for assisting targeting. APPROACH: Electrode arrays were constructed with two different diameters of 0.65 mm and the standard 1.3 mm. Micro-electrodes were incorporated into the slim electrode arrays for recording spiking neural activity. Arrays were bilaterally implanted into the medial geniculate body (MGB) in nine anaesthetised cats for 24-40 h using stereotactic techniques. Recordings of auditory evoked field potentials and multi-unit activity were obtained at 1 mm intervals along the electrode insertion track. Insertion trauma was evaluated histologically. MAIN RESULTS: Evoked auditory field potentials were recorded from ring and micro-electrodes in the vicinity of the medial geniculate body. Spiking activity was recorded from 81% of the microelectrodes approaching the MGB. Histological examination showed localized surgical trauma along the implant. The extent of haemorrhage surrounding the track was measured and found to be significantly reduced with the slim electrodes (541 ± 455 µm vs. 827 ± 647 µm; P < 0.001). Scoring of the trauma, focusing on tissue disruption, haemorrhage, oedema of glial parenchyma and pyknosis, revealed a significantly lower trauma score for the slim electrodes (P < 0.0001). SIGNIFICANCE: The slim electrodes reduced the extent of acute trauma, while still providing adequate electrode impedance for both stimulating and recording, and providing the option to target stimulate smaller volumes of tissue. The incorporation of microelectrodes into the electrode array may allow for a simplified, single-step surgical approach where confirmatory micro-targeting is done with the same lead used for permanent implantation.

Persistent hiccups and Horner's syndrome in a case of primary CNS lymphoma with diffuse cerebral, hypothalamic and lateral brainstem involvement - An exercise in clinical neuroanatomy.

We present a case of a 42-year-old male presenting with persistent hiccups and a Horner's syndrome, among other symptoms and signs of hypothalamic and brainstem dysfunction. He had a biopsy-proven diffuse infiltrative large primary CNS B-cell lymphoma involving the left fronto-temporal hemisphere, diencephalon and brainstem. The aim of this case report is to highlight key clinical and neuro-anatomical correlations that bring light to the art of the clinical examination.

Preclinical evaluation of a miniaturized Deep Brain Stimulation electrode lead.

The effect of miniaturizing the electrode lead for Deep Brain Stimulation (DBS) therapy was investigated in this work. A direct comparison was made between a miniature lead (0.65 mm diameter) and a lead of standard size (1.3 mm). Acute in vivo implantation in two cat brains was performed to evaluate surgical trauma and confirm capacity to target thalamic nuclei. Insertion into a homogeneous gel model of neural tissue was used to compare insertion forces while visualizing the process. The standard size cannula, used first to guide lead insertion, required substantially higher insertion force compared with the miniature version and produced a significantly larger region of tissue disruption. The characteristic hemorrhage and edema extended 119-352 µm from the implanted track surface of the miniature lead and cannula, while these extended 311-571 µm for the standard size lead and cannula. A miniature DBS implant can reduce the extent of trauma and could potentially help improve neural function preservation after functional neurosurgery.

Double pituitary adenomas: a series of three patients.

Multiple pituitary adenomas may occur in up to 1.6-3.3% of patients with Cushing's syndrome. We report three patients with double pituitary adenomas detected at surgery. Two patients had Cushing's disease, but trans-sphenoidal exploration revealed a small prolactinoma in each. One prolactinoma also contained small numbers of basophils. Re-operation in both patients because of persistent Cushing's syndrome showed an ACTH-secreting micro-adenoma. The third patient with acromegaly had two macro-adenomas discovered in different parts of the gland at surgery: one plurihormonal and one null cell tumour. Careful evaluation of pre-operative MRI may not always detect more than one pituitary adenoma.

Unilateral pallidotomy for Parkinson's disease disrupts ocular fixation.

Although some motor functions of the basal ganglia have been well studied, the oculomotor functions are not well established. We studied eye movements in patients with Parkinson's disease (PD) undergoing pallidotomy to assess the role of the globus pallidus interna (GPi) in oculomotor control. Horizontal visually guided, gap and predictive saccades as well as ocular fixation were studied in patients with advanced PD before and 1 month after unilateral pallidotomy, and in healthy controls on two occasions 1 month apart. There was no difference in saccadic latency or accuracy, the number of saccadic anticipations or the ability to generate predictive saccades between the two assessments for either patients or controls. The number and amplitude of square wave jerks during ocular fixation however increased significantly in patients after pallidotomy. The results imply altered function of frontal or prefrontal cortical regions involved in ocular fixation resulting from a disruption to inhibitory pallidal influences on thalamocortical projections. The posteroventral GPi however appears not to be involved in externally controlled or predictive saccadic function.

Neurochemical, hormonal, and behavioral effects of chronic unpredictable stress in the rat.

The high comorbidity of anxiety and depression suggests a potential degree of commonality in their etiologies. The chronic unpredictable stress (CUS) model effectively replicates depressive-like phenotypes; however, the ability of CUS to produce anxiety-like behaviors has not been adequately addressed. Using the CUS paradigm (2 stressors per day for 10 days) in adult Sprague-Dawley rats we identified behavioral, hormonal, and neurochemical changes one day after the cessation of treatment. Stress attenuated weight gain throughout the study and increased locomotor activity one day after treatment, but had no effect on anxiety-behavior as measured by the elevated plus maze. In addition, plasma corticosterone levels were positively correlated with hypothalamic serotonin (5-HT) activity one day after stress treatment as determined by the ratio of the metabolite 5-hydroxyindoleacetic acid (5-HIAA) to the parent compound (5-HIAA/5-HT ratio). These data suggest behavioral phenotypes associated with depression, but not comorbid anxiety, emerge in the immediate period after cessation of stress and that stress related physiology is related to 5-HT activity in the hypothalamus.