White matter connectivity disruptions in early and chronic schizophrenia.

BACKGROUND: White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages. METHODS: Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic). RESULTS: Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01). CONCLUSIONS: Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.

Longitudinal employment outcomes of an early intervention vocational rehabilitation service for people admitted to rehabilitation with a traumatic spinal cord injury.

STUDY DESIGN: Longitudinal cohort design. OBJECTIVES: First, to explore the longitudinal outcomes for people who received early intervention vocational rehabilitation (EIVR); second, to examine the nature and extent of relationships between contextual factors and employment outcomes over time. SETTING: Both inpatient and community-based clients of a Spinal Community Integration Service (SCIS). METHODS: People of workforce age undergoing inpatient rehabilitation for traumatic spinal cord injury were invited to participate in EIVR as part of SCIS. Data were collected at the following three time points: discharge and at 1 year and 2+ years post discharge. Measures included the spinal cord independence measure, hospital anxiety and depression scale, impact on participation and autonomy scale, numerical pain-rating scale and personal wellbeing index. A range of chi square, correlation and regression tests were undertaken to look for relationships between employment outcomes and demographic, emotional and physical characteristics. RESULTS: Ninety-seven participants were recruited and 60 were available at the final time point where 33% (95% confidence interval (CI): 24-42%) had achieved an employment outcome. Greater social participation was strongly correlated with wellbeing (ρ=0.692), and reduced anxiety (ρ=-0.522), depression (ρ=-0.643) and pain (ρ=-0.427) at the final time point. In a generalised linear mixed effect model, education status, relationship status and subjective wellbeing increased significantly the odds of being employed at the final time point. Tertiary education prior to injury was associated with eight times increased odds of being in employment at the final time point; being in a relationship at the time of injury was associated with increased odds of being in employment of more than 3.5; subjective wellbeing, while being the least powerful predictor was still associated with increased odds (1.8 times) of being employed at the final time point. CONCLUSIONS: EIVR shows promise in delivering similar return-to-work rates as those traditionally reported, but sooner. The dynamics around relationships, subjective wellbeing, social participation and employment outcomes require further exploration.

Reducing the length of stay for acute hospital patients needing admission into inpatient rehabilitation: a multicentre study of process barriers.

BACKGROUND: Patient flow is a major problem in hospitals. Delays in accessing inpatient rehabilitation have not been well studied. AIMS: Measure the time taken for key processes in the patient journey from acute hospital admission through to inpatient rehabilitation admission in order to identify opportunities for improvement. METHODS: Retrospective open cohort study. All patients admitted over 8- and 10-month periods during 2008 into two inpatient rehabilitation units in Melbourne, Australia. Main outcome measures were the duration of the following key processes: acute hospital admission until referral for rehabilitation, referral until assessment by the rehabilitation service, assessment until deemed ready for transfer to rehabilitation, ready for transfer until rehabilitation admission. RESULTS: Three hundred and sixty patients were in the study sample (females = 186; 51.7%); mean age = 58.4 (standard deviation = 15.0) years. There was a median of 7 (interquartile range [IQR] 4-13) days from acute hospital admission till referral for rehabilitation, a median of 1 (IQR 0-1) day from referral till assessment, a median of 0 (IQR 0-2) days from assessment till deemed ready for transfer and a median of 1 (IQR 0-3) day from ready till admission into rehabilitation. Overall, patients spent 12.0% (804/6682) of their acute hospital admission waiting for a rehabilitation bed. CONCLUSIONS: There are opportunities to improve the efficiency of key processes in the acute hospital journey for patients subsequently admitted to inpatient rehabilitation; in particular, reducing the time from acute hospital admission till referral for rehabilitation and from being deemed ready for transfer to rehabilitation till admission.

Botulinum toxin assessment, intervention and aftercare for lower limb disorders of movement and muscle tone in adults: international consensus statement.

Lower limb disorders of movement and muscle tone in adults significantly impact quality of life. The management of the patient with hypertonia is complex and requires a multidisciplinary team working with the patient and family/carers. Botulinum neurotoxin type A (BoNT-A) has been used as a component of this management to reduce lower limb hypertonia, increase passive range of motion and reduce associated pain and requirements for bracing. Adjunctive treatments to augment the effect of BoNT-A include electrical muscle stimulation of the injected muscles and stretching. When determining suitability for injection, the patient's main goals for intervention need to be established. Muscle overactivity must be distinguished from contracture, and the effect of underlying muscle weakness taken into account. Explanation of the injection process, potential adverse effects and post-injection interventions is essential. Assessment at baseline and post-treatment of impairments such as hypertonia, range of motion and muscle spasm are appropriate; however, the Goal Attainment Scale and other validated patient-centred scales can also be useful to assess therapy outcomes. In the future, initiatives should be directed towards examining the effectiveness of BoNT treatment to assist with achievement of functional and participation goals in adults with hypertonia and dystonia affecting the lower limb.

Stroke rehab down under: can Rupert Murdoch, Crocodile Dundee, and an Aboriginal elder expect the same services and care?

Australia is the world's sixth largest country, has a relatively small population of 21.5 million, and a blended (public and private) health system. In this article, we explain the stroke rehabilitation infrastructure including consumer organisations, research networks, data collection systems, and registries. This represents a complex but fledgling set of organisations showing great promise for coordination of care and research. The article goes on to expose the inequalities in service provision by describing the paths of stroke survivors in three settings - in the city, in the country, and in remote settings. The complexities and difficulties in treating indigenous stroke survivors are described in a culturally sensitive narrative. The article then discusses the outcomes of the first Australian audit of post acute stroke services completed in December 2008, which describes the journeys of 2,119 stroke survivors at 68 rehabilitation units throughout Australia's 6 states and 2 territories. It demonstrates an average length of stay of 26 days, with 18% of survivors requiring nursing home or other supported accommodation. The article concludes with future directions for stroke rehabilitation in Australia, which include hyperacute rehabilitation trials, studies in 7-days-a-week rehabilitation, and the potential use of robotics.

Image guidance removal of a foreign body in the orbital apex.

Retrieval of foreign bodies lodged in the orbit present a challenging surgical problem. The trans-nasal approach when combined with image-guided navigation allows clear identification of structures and increased safety. We report a case of a successful removal of a foreign body under image-guidance using a trans-nasal approach.

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

BACKGROUND: The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. AIM: To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. DESIGN: A prospective, Australian, multicentre, randomized controlled trial. SETTING: Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. SUBJECTS: 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). RANDOMIZATION: Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). INTERVENTION: Exposure to the ICARUSS model of integrated care or usual care. PRIMARY OUTCOME: The composite of stroke, MI or death from any vascular cause, whichever occurs first. SECONDARY OUTCOMES: Risk factor management in the community, depression, quality of life, disability and dementia. STATISTICAL POWER: With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points CONCLUSION: The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level.

Quantitative morphology of human retrolaminar optic nerve vasculature.

PURPOSE: To quantify the variation in the blood supply of the retrolaminar optic nerve in humans. The retrolaminar anterior optic nerve is supplied by an elliptical arterial "circle" of Haller and Zinn formed by anastomoses around the optic nerve between medial and lateral paraoptic short posterior ciliary arteries (PO-SPCAs). The frequency with which complete perioptic nerve arteriolar anastomoses (PONAA) occur is unknown, yet they form the basis for many postulated pathophysiological mechanisms. METHODS: Scanning electron microscopy was performed on 25 orbital and ocular microvascular corrosion casts (methyl methacrylate) from 20 human cadavers of subjects 21 to 97 years of age without known ocular disease. RESULTS: Eighteen casts were examined in detail after microdissection (the analysis of seven casts was limited because of their fragility). In 15/18 (83%) casts, the PONAA were supplied by branches of a medial and lateral PO-SPCA; in 2/18, they were supplied by one (lateral) PO-SPCA; and in 1/18, they were supplied by a superior PO-SPCA and two horizontal PO-SPCAs. The PONAA had intact superior and inferior anastomoses in 8/18 (44%) casts, anastomoses with narrowed portions in 6/18 (33%), and incomplete in 4/18 (23%). Narrowed portions were not preferentially distributed to either superior or inferior anastomoses. CONCLUSIONS: Complete PONAA was found in more than 75% of casts, including anastomoses with narrow portions in 33% of casts.

Well-differentiated squamous cell carcinoma of the eyelid arising during a 20-year period.

An 81-year-old man had a keratotic eyelid lesions for 20 years. He eventually sought treatment by ophthalmic plastic surgery. Clinically, the lesion resembled a keratoacanthoma. Findings from histologic examination of the excision biopsy specimen showed a squamous cell carcinoma. The lesion was completely excised. This case demonstrates the difficulty in making a correct clinical diagnosis of a keratotic eyelid lesion. Performing a histologic examination of nonregressed keratotic lesions is essential to exclude a squamous cell carcinoma.

Third-generation antidepressants: do they offer advantages over the SSRIs?

Third-generation antidepressants are a group of antidepressant agents of variable action, not confined to serotonin reuptake inhibition. These agents include venlafaxine, reboxetine, nefazodone and mirtazapine. Claims have been made for these agents in terms of improved efficacy, faster speed of onset of effect and greater safety in the treatment of depression compared with previous medications, such as the selective serotonin reuptake inhibitors (SSRIs). This article reviews the evidence for these improvements. Thirty active comparator studies were reviewed involving the third-generation antidepressant agents. While there were isolated reports of improvements over comparator agents for venlafaxine, reboxetine and mirtazepine, there were no convincing differences between third-generation agents and comparators in terms of overall efficacy, relapse prevention and speed of onset. The third-generation antidepressants were, however, of equivalent safety to SSRIs and maintained improvements in safety over first-generation agents.

Analysis of the syndrome of unilateral neglect.

Using a variety of clinical measures of unilateral neglect 40 right hemisphere lesioned stroke subjects were compared in terms of neuropsychological deficit. The results of the study encourage the view that unilateral neglect is a complex syndrome and subjects who indicate the disorder may vary in systematic dimensions. There are at least two factors contributing to the neglect syndrome--a scanning factor of external stimuli and a disrupted internal representation of space factor. Both the obtained factors were correlated with functional independence at 6 months post-stroke in a further group of 27 right hemisphere lesioned stroke patients. It is probable that most commonly these factors co-exist and form the classical neglect syndrome but theoretically they may occur separately and this leads to implications for management.

Keratomalacia on a 'healthy diet'.

The case is described of a 39-year-old man with previously undiagnosed chronic schizophrenia and with bilateral keratomalacia secondary to his bizarre diet. He presented with a perforation of the right cornea which required an emergency penetrating keratoplasty. The difficulties of clinical management of a patient with an overt psychosis and the use of serum retinol levels to monitor treatment are described. Causes of vitamin A deficiency seen in Great Britain are discussed.

Botulinum toxin A treatment of overactive corrugator supercilii in thyroid eye disease.

BACKGROUND/AIM: Patients with thyroid eye disease with upper eyelid retraction often develop overaction of the accessory muscles of eyelid closure, the glabellar muscles corrugator supercilii and procerus. The resultant glabellar furrowing (frown lines) contributes to the typical thyroid facies. The aim of this study was to evaluate the use of botulinum toxin A reversible chemodenervation of the glabellar muscles as adjunctive treatment in the rehabilitation of patients with thyroid eye disease. METHODS: 14 patients (13 females) ages 39-76 years (mean 52) with inactive thyroid eye disease and associated medial eyebrow ptosis and prominent glabellar frown lines were recruited. All patients had a history of upper eyelid retraction. Each patient was treated with a single botulinum toxin injection (Dysport 0.2 ml, 40 units) into each corrugator supercilii and sometimes procerus muscles as an outpatient procedure. The effectiveness and acceptability of the treatment was assessed clinically and from a patient questionnaire. RESULTS: The injections were tolerated by 13/14 (93%) patients. There was resultant flattening of the glabellar region and improvement of medial eyebrow contour in all patients, with onset of paralysis within 1 week. All patients reported a subjective improvement in appearance. Side effects included one patient (7%) with reversible partial ptosis. The beneficial effect lasted 4-6 months, with a gradual return of function. Repeat treatment was indicated where there was persistent upper eyelid retraction and protractor overaction. CONCLUSION: Botulinum toxin A chemodenervation of the glabellar muscles in these patients was effective and acceptable. Chemodenervation should be considered in the rehabilitation of patients with thyroid eye disease where there is upper eyelid retraction and overacting protractors resulting in a thyroid frown. Once the eyelid retraction has been successfully treated by surgery, the need for further glabella muscle chemodenervation is considerably reduced.

Acquired Brown's syndrome in a patient with combined lichen sclerosus et atrophicus and morphoea.

A 49-year-old woman with generalised lichen sclerosus et atrophicus and morphoea developed bilateral Brown's syndrome. Some of the skin lesions were in the vicinity of the trochlea. A characteristic feature of morphoea is subcutaneous fibrosis, so we postulate that the cause of the Brown's syndrome was mechanical tethering of the superior oblique tendon by deep subdermal fibrosis. Histopathological diagnosis was made from biopsies of similar lesions on the patient's face.

Raising the suborbicularis oculi fat (SOOF): its role in chronic facial palsy.

AIMS: To determine the adjuvant role of unilateral suborbicularis oculi fat (SOOF) lift in the periorbital rehabilitation of patients with chronic facial palsy. METHODS: In a non-comparative prospective case series nine adult patients (seven male, two female) aged 34-90 years (mean 60.5) with chronic unrecovered facial palsy (over 1 year), who had not had any previous rehabilitative periorbital surgery, were studied. Lateral tarsal strip and adjuvant transconjunctival approach subperiosteal SOOF lift under local or general anaesthesia were performed; medial canthoplasty was performed where indicated. There was clinical observation of the long term (over 1 year) effect on the ptotic palpebral-malar sulcus and lower eyelid retraction. RESULTS: The patients were followed up for 12-24 months (mean 16). Seven patients (77%) had sustained clinical reduction of palpebral-malar sulcus ptosis. All patients had sustained reduction of lagophthalmos. Early postoperative complications included conjunctival cheimosis in 77%. Three patients with persistent keratitis required further surgical procedures on their upper eyelid to reduce the palpebral aperture. There were no cases of infraorbital nerve anaesthesia or recurrent lower eyelid retraction. CONCLUSIONS: The SOOF lift has an adjuvant role in chronic facial palsy with lower eyelid retraction and ptotic-palpebral malar sulcus. It supports the lower eyelid elevation and tightening achieved with the lateral tarsal strip. The best results were obtained in congenital facial palsy.

Autogenous temporalis fascia patch graft for porous polyethylene (Medpor) sphere orbital implant exposure.

BACKGROUND: Temporalis fascia has been recommended for hydroxyapatite sphere exposure. The aim of this study was to identify potential risk factors for exposure of porous polyethylene (Medpor) sphere implants and evaluate the use of autogenous temporalis fascia as a patch graft for exposure. METHODS: A retrospective review of consecutive cases of porous polyethylene sphere orbital implant exposure. RESULTS: Five cases presented between May 2000 and October 2001 (three males, two females; mean age 44.5 years). Three had enucleation (two with primary implants) and two had evisceration (one with primary implant). Exposure occurred in one primary, two secondary, and two replacement implants. Orbital implant diameter was 20 mm in four cases and 16 mm in one case (contracted socket). The mean time from implantation to exposure was 23 months (range 0.7-42.6). Three patients had secondary motility peg placement before exposure. The average time from last procedure (sphere implant or peg insertion) to exposure was 3 months (range 0.7-12.6). Four patients required surgical intervention, of which three needed more than one procedure. Autogenous temporalis fascia grafting successfully closed the defect without re-exposure in three of these four patients. The grafts were left bare in three patients, with a mean time to conjunctivalise of 2.4 months (range 1.6-3.2). CONCLUSIONS: Exposed porous polyethylene sphere implants were treated successfully with autogenous temporalis fascia graft in three of four patients. This technique is useful, the graft easy to harvest, and did not lead to prolonged socket inflammation, infection, or extrusion.

Early treatment of juvenile xanthogranuloma of the iris with subconjunctival steroids.

Five infants with biopsy proved juvenile xanthogranuloma of the iris were reviewed. Early treatment with subconjunctival injection of steroids and topical steroid drops resulted in regression of the lesion in four patients. One patient, reviewed at the age of 8 months after glaucoma which had developed secondary to the iris xanthogranuloma, had been treated by surgery alone: the visual outcome was very poor.

Functional results and complications of Mersilene mesh use for frontalis suspension ptosis surgery.

AIMS: To assess the functional results and complications of Mersilene (polyester) mesh frontalis sling suspension to correct poor levator function ptosis. METHODS: Retrospective case series. 32 eyelids of 20 patients (12 children and eight adults). RESULTS: Follow up 1-69 months (mean 32). CHILDREN: eight patients had bilateral and four unilateral surgery (20 eyelids). Good long term functional results were achieved in 73% (8/11 children) and 77% (14/18) eyelids. Two children had early postoperative wound infection requiring removal of mesh in one; the other was lost to follow up following medical treatment. ADULTS: four patients had bilateral and four unilateral surgery (12 eyelids). Good long term functional results were achieved in 75% (6/8 patients, 9/12 eyelids). One postoperative wound infection and one mesh exposure were treated definitively by surgical excision of mesh. CONCLUSION: Mersilene mesh provides good functional results but up to 20% of patients have early soft tissue complications. Other materials such as monofilament suture or autogenous fascia lata should be considered.

The use of porous polyethylene (Medpor) lower eyelid spacers in lid heightening and stabilisation.

BACKGROUND/AIMS: The management of lower eyelid retraction can be challenging, and established techniques to correct it are not always successful. Previous reports have suggested a role for the ultrathin high density porous polyethylene lower eyelid spacer (Medpor LES) in such patients. The authors report the experience of three surgeons implanting Medpor LES over 1 year, and ascertain whether such implants are a safe and effective alternative to autogenous spacers. METHODS: A prospective, interventional, non-comparative case series of consecutive patients. Surgical indications for Medpor LES were noted. Preoperative and postoperative lower marginal reflex distance (L-MRD), vertical palpebral aperture (PA), lagophthalmos, and scleral show inferior to the limbus (LSS) were recorded, together with major and minor complications. RESULTS: 32 patients (35 eyelids) had a Medpor LES inserted, 22/32 under local anaesthetic, and nine with adjunctive procedures. Mean follow up was 22 months (range 15-28 months). The Medpor LES was effective in reducing the palpebral aperture (p<0.001) and lagophthalmos (p = 0.04) and raising the lower eyelid height by reducing both L-MRD (p = 0.006) and LSS (p<0.001). However there were major complications in 7/32 patients and minor complications in 8/32, most requiring further surgery. Final outcome was good in 24/35 eyelids and satisfactory in 5/35. CONCLUSIONS: Despite a good or satisfactory final outcome in the majority of patients, the value of this technique is limited by complications, and should be reserved for those unsuitable for safer techniques.