Stickler syndrome - lessons from a national cohort.

In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families. Using a combination of accurate phenotyping and molecular genetic analysis it is possible to identify the underlying genetic mutation in over 95% of cases including those with deep intronic mutations likely to be missed by conventional exome panel analysis and which require whole gene sequencing and supplementary functional analysis to confirm pathogenicity. The vast majority that presents to ophthalmologists will be from one of three autosomal dominant sub-groups with a high associated risk of retinal detachment but the diagnosis is often overlooked, especially in adults. In contrast to many other blinding retinal conditions, blindness through giant retinal tear detachment particularly in children is largely preventable provided these high-risk groups are identified and appropriate evidence-based prophylaxis offered. This article summarises ten selected briefcase histories from the national dataset with key learning points from each.

Magnetic resonance image findings in the early post-operative period after anterior cervical discectomy.

If early neurological deterioration occurs following anterior cervical discectomy, the patient should be evaluated by urgent MRI scanning. In order to interpret such a scan it is essential to know what the normal post-operative MRI appearance is following an uncomplicated procedure. In the lumbar spine it is well recognized that early post-operative imaging following discectomy is difficult to interpret with a high rate of false positive scans. The normal appearance of MRI in the early post-operative period was evaluated prospectively in 15 patients undergoing anterior cervical discectomy without fusion for either cervical radiculopathy or myelopathy. MRI was performed on the first post-operative day, at 6 weeks and 6 months. The successful outcome of the procedure was validated by uniform improvement of Visual Analogue Scale measurement for neck and arm pain, the Neck Disability Index and European Myelopathy Score as appropriate. In contrast to the established findings following lumbar discectomy, only two cases showed a persistent epidural mass in the first post-operative scan and this had completely resolved at 6 months. All patients had foraminal narrowing and root or cord compression pre-operatively. Sixty six percent of cases showed persistent foraminal narrowing on sequential imaging up to 6 months despite showing good symptomatic improvement. All cases demonstrated high signal in the operated disc space on T2 weighted imaging on the first post-operative day and this finding persisted in 13 of 15 scans performed at 6 weeks. Post contrast imaging demonstrated no enhancement of operated disc space and adjacent vertebral body on the first post-operative day, whereas all scans at 6 weeks showed enhancement and such enhancement persisted at 6 months in 50%. Persistent epidural filling defects are uncommon following successful anterior cervical discectomy but persistence of foraminal narrowing is common despite successful outcome. Enhancement of the disc space is also common and does not in itself imply infection.

Repeat autoclaving does not remove protein deposits from the classic laryngeal mask airway.

INTRODUCTION: We tested the hypothesis that repeated autoclaving removes protein deposits from the classic laryngeal mask airway (LMA). METHODS: Twenty previously used LMAs were hand washed, machine washed, dried, autoclaved and randomly allocated into four equal-sized groups for repeat autoclaving on 0 (control), 1, 2 and 3 occasions. After the final autoclave cycle, the LMAs were immersed in a protein-staining solution, rinsed, dried and a high-resolution digital image taken of the dorsal and ventral surfaces. The severity of staining was scored by two blinded observers. RESULTS: All LMAs were stained. There was no reduction in staining with repeat autoclaving. CONCLUSIONS: Repeat autoclaving does not remove protein deposits from the LMA.

Intracerebral abscess formation following embolisation of an internal carotid artery aneurysm using Guglielmi detachable coils.

Infection following endovascular therapy for cerebrovascular disease is a potential but rare complication. A 70-year-old lady in whom an intracranial abscess formed secondary to GDC embolisation of a giant right internal carotid artery aneurysm is reported. Computed tomography (CT) showed the abscess and staphylococcus aureus was cultured from the cerebrospinal fluid and blood. The abscess was successfully treated by antibiotic therapy. Infected Guglielmi detachable coils (GDC) may result in abscess formation in the presence of underlying cerebral ischaemia.

Airway rescue with the ProSeal laryngeal mask airway in the intensive care unit.

We report the successful use of the ProSeal laryngeal mask airway for airway rescue in a 41-year-old septic patient who could be neither intubated nor facemask ventilated. In principle, the ProSeal laryngeal mask airway offers advantages over the Classic LMA in this situation.

Occupational exposure to organic solvents and long-term nervous system damage detectable by brain imaging, neurophysiology or histopathology.

The purpose of the present review is to assess the evidence published in scientific literature that industrial organic solvents as a generic group have the ability to induce long-term nervous system damage in workers that can be detected by techniques other than neuropsychological testing. The main body of evidence considered in this review was 40 studies involving the use of brain imaging, neurophysiological testing, gross autopsy or histopathology in groups of workers with long-term solvent exposure. Case reports involving both solvent abuse and occupational exposure, and experimental animal data have also been reviewed as supporting data. A number of the studies in groups of workers provide evidence of the presence of marginal atrophic abnormalities in the brain or deficits in nerve conduction velocity in solvent-exposed workers. However, there are limitations in the design of many of these studies, the strength of association between exposure and effect is not consistently strong, no dose-response relationship can be detected, the reported changes lack specificity and there is no coherence between the human and experimental animal data. Overall, it is not possible to draw reliable conclusions with respect to the presence or absence of nervous system damage related to the common properties of organic solvents.

A national survey of attitudes towards the use of MRI in patients known to have intracranial aneurysm clips.

The objective of this study was to determine the attitudes and practice of neuroradiology centres across the UK regarding the use of MRI in patients known to have intracranial aneurysm clips. A postal survey comprising three questions and a comments section was sent to 35 neuroradiology centres across the UK. There were 32 (91%) respondents to the single questionnaire. 16 (50%) respondents said that they would not consider performing MRI on a patient with an intracranial aneurysm clip. Of the remaining 50%, all said that identification of the clip type and assurance of its safety would be needed prior to scanning the patient. The magnetic strength of the system did not appear to affect the decision regarding whether or not to perform MRI on such patients. There was a variation in attitude towards the use of MRI in such patients between different regions. Neuroradiology centres are equally divided in their attitude and practice about whether it is safe to use MR to image a patient known to have an intracranial aneurysm clip. This is most probably due to the conflicting literature, as well as uncertainty about the identification and ferromagnetic properties of individual clips.

Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR.

Recent 13C NMR studies in rat models have shown that the glutamate/glutamine cycle is highly active in the cerebral cortex and is coupled to incremental glucose oxidation in an approximately 1:1 stoichiometry. To determine whether a high level of glutamatergic activity is present in human cortex, the rates of the tricarboxylic acid cycle, glutamine synthesis, and the glutamate/glutamine cycle were determined in the human occipital/parietal lobe at rest. During an infusion of [1-13C]-glucose, in vivo 13C NMR spectra were obtained of the time courses of label incorporation into [4-13C]-glutamate and [4-13C]-glutamine. Using a metabolic model we have validated in the rat, we calculated a total tricarboxylic acid cycle rate of 0.77 +/- 0.07 micromol/min/g (mean +/- SD, n = 6), a glucose oxidation rate of 0.39 +/- 0.04 micromol/min/g, and a glutamate/glutamine cycle rate of 0.32 +/- 0.05 micromol/min/g (mean +/- SD, n = 6). In agreement with studies in rat cerebral cortex, the glutamate/glutamine cycle is a major metabolic flux in the resting human brain with a rate approximately 80% of glucose oxidation.

Carotico-cavernous fistula following septorhinoplasty.

Septorhinoplasty is a very common operation in otolaryngological practice. We report the second case of a carotico-cavernous fistula following septorhinoplasty. This case presented with very severe epistaxis before the appearance of the typical pulsating exophthalmos, ophthalmoplegia, headache and engorged veins on the right side of the face. Our case was treated by endovascular thrombosis with electrolytically detachable coils.

Responses of red foxes to first and second infection with Sarcoptes scabiei.

The clinical response of red foxes (Vulpes vulpes) to the mange mite, Sarcoptes scabiei, was characterized by infection of five, 4-mo-old red foxes with S. scabiei originally isolated from a wild red fox. The infected foxes and three uninfected control foxes were monitored with weekly complete blood counts and biweekly serum chemistry profiles, hypersensitivity tests, and evaluation of skin biopsies. After 7 wk, the foxes were treated and held free of infection for 2 mo. Six foxes, three previously infected and three with no history of exposure, were then infected with the same isolate of S. scabiei and followed for another 7 wk; two additional previously infected foxes were held as treatment controls, and two foxes with no history of exposure as naive controls. All infected foxes developed significant immediate (Type I) hypersensitivity reactions to a S. scabiei mite extract within 2 wk of exposure and maintained this reaction as long as 4 mo after clearance of mites. Pronounced mast cell hyperplasia and infiltration with eosinophils were the earliest inflammatory cell responses noted in biopsy samples from infected foxes and were maintained throughout infection. Infected foxes also showed significant increases in white blood cell counts, due primarily to increases in numbers of circulating neutrophils and eosinophils. Clinical response, severity of disease, and relative numbers of mites per cm2 of skin of previously infected foxes and foxes undergoing their first infection did not differ. These results show that red foxes develop strong immediate hypersensitivity reactions to S. scabiei but, under our experimental conditions, did not exhibit resistance to reinfection.

Dynamic shim updating: a new approach towards optimized whole brain shimming.

The static magnetic field within two widely spaced axial slices of the human brain was mapped in five subjects following global shimming. This revealed a first order field shift in the anterior-posterior direction between the cerebellum and cerebrum, which has implications for functional and spectroscopic magnetic resonance imaging. A new method is described called dynamic shim updating (DSU) to compensate for these field differences whereby the shim correction fields are updated in real time during multislice data acquisition to match the current imaging or spectroscopy slice. A hardware unit is presented to demonstrate the method using the first order shim corrections, which can be updated virtually instantaneously between slice acquisitions to give optimal shimming of each slice. The efficiency of the approach is demonstrated using field mapping and high speed MR imaging (echo-planar imaging), which are sensitive to field inhomogeneity.

Variability in measurement of extracranial internal carotid artery stenosis as displayed by both digital subtraction and magnetic resonance angiography: an assessment of three caliper techniques and visual impression of stenosis.

BACKGROUND AND PURPOSE: The degree of stenosis in the extracranial internal carotid artery helps predict the risk of an individual suffering subsequent cerebrovascular ischemic events. Different techniques have evolved to measure stenosis from angiograms, leading to some confusion and a call for the adoption of a single technique. To help choose the most reliable technique, this study assessed observer variability in reporting carotid stenosis for four different techniques, from both digital subtraction (DSA) and MR angiograms (MRA). Three of the techniques used caliper measurements; the fourth was the visual impression of stenosis. METHODS: From a total of 137 angiograms, caliper measurements were possible on 105 DSAs and 74 MRAs. Measurements from these angiograms were made by two independent observers on two separate occasions to assess interobserver and intraobserver variation in reporting. RESULTS: For DSA, the variability in reporting and the number of clinically significant differences arising as a result were similar for each of the four techniques. While the typical measurement errors for each of the techniques studied were on the order of +/- 5%, each technique produced some sizable individual differences for the same angiogram, with resultant wide 95% limits of agreement. Observer variability for reporting MRA was generally a little greater than for DSA. Compared with the caliper techniques, the visual impression of stenosis technique performed well, particularly for MRA. CONCLUSIONS: Although observer variability in reporting can be considerable, no important differences were found among the different techniques widely used for measuring carotid stenosis.

Demonstration of neurovascular compression in trigeminal neuralgia with magnetic resonance imaging. Comparison with surgical findings in 52 consecutive operative cases.

Until recently, the inability to demonstrate neurovascular compression of the trigeminal nerve preoperatively resulted in surgery being offered only in cases of severe trigeminal neuralgia (TGN), frequently after a prolonged trial of medical treatment and following less invasive procedures, despite the fact that posterior fossa microvascular decompression gives long-term pain relief in 80% to 90% of cases. To assess whether vascular compression of the nerve could be demonstrated preoperatively, high definition magnetic resonance tomographic angiography (MRTA) was performed in 50 consecutive patients, five of whom had bilateral TGN, prior to posterior fossa surgery. The imaging results were compared with the operative findings in all patients, including two patients who underwent bilateral exploration. Vascular compression of the trigeminal nerve was identified in 42 of 45 patients with unilateral symptoms and on both sides in four patients with bilateral TGN. In the last patient with bilateral TGN, neurovascular compression was identified on one side, and on the other side the compressing superior cerebellar artery was separated from the nerve by a sponge placed during previous surgery. There was full agreement regarding the presence or absence of neurovascular compression demonstrated by MRTA in 50 of 52 explorations, but MRTA misclassified four vessels compressing the trigeminal nerve as arteries rather than veins. In two cases, there was disagreement between the surgical and MRTA findings. In the first of these cases, surgery revealed distortion of the nerve at the pons by a vein that MRTA had predicted to lie 6 mm remote from this point. In the second patient, venous compression was missed; however, this patient was investigated early in the series and did not have gadolinium-enhanced imaging. In nine cases, MRTA correctly identified neurovascular compression of the trigeminal nerve by two arteries. Moreover, MRTA successfully guided surgical reexploration in one patient in whom a compressing vessel was missed during earlier surgery and also prompted exploration of the posterior fossa in two patients with multiple sclerosis and one patient with Charcot-Marie-Tooth syndrome, in whom neurovascular compression was identified preoperatively. It is concluded that MRTA is an extremely sensitive and specific method for demonstrating vascular compression in TGN. As a result, open surgical procedures can be recommended with confidence, and microvascular decompression is now the treatment of choice for TGN at the authors' unit. They propose MRTA as the definitive investigation in such patients in whom surgery is contemplated.

Traumatic aneurysm of the maxillary artery: the role of interventional radiology. A report of two cases.

Two cases of post-traumatic aneurysm of the maxillary artery are described. The first patient was a 20-year-old man who sustained a Le Fort III type fracture in a road traffic accident. He experienced two episodes of significant maxillofacial haemorrhage, the first following admission and the second 5 days after initial reduction and fixation of his midfacial fractures. The second patient was a 23-year-old man with a bilateral cleft palate and extreme midfacial hypoplasia who underwent Le Fort I osteotomy. Significant bleeding commenced 3 h postoperatively and was not completely controlled by anterior and posterior nasal packing. Both the aneurysms were diagnosed on selective carotid angiography and successfully treated by embolization.

Changes in muscle mechanics during chronic conditioning for cardiomyoplasty.

Chronic repetitive stimulation of skeletal muscle causes significant changes in contractile mechanics and makes the muscle fatigue resistant. The purpose of this study was to quantify the magnitude and time course of these changes. One latissimus dorsi muscle from each of 28 mongrel dogs was stimulated in situ at 1 Hz for 0, 3, 7, 14, 21, 42, or 70 days. Changes in isometric and isotonic mechanical performance were measured as a function of conditioning time. Isotonic force and velocity data were fitted to the Hill equation to obtain Vmax. The most striking early change was a 30 and 26% decline in muscle mass and cross-sectional area, respectively. Coincident with this was an approximate 40% decline in tetanic and twitch tension. There was a similar decline in the rates of rise and fall of twitch and tetanus tensions (+dT/dt and -dT/dt). The decline in tetanus +dT/dt and -dT/dt followed a similar time course, suggesting that these muscle functions were under similar influences. Calculation of the isometric force data per unit of cross-sectional area minimized the effect of stimulation on isometrically measured muscle function but did not eliminate it. Fusion frequency declined 52% with conditioning. The increases in time-to-peak twitch tension and half-relaxation time were independent of cross-sectional area. Time-to-peak twitch tension and half-relaxation time increased after 7 days of stimulation and became maximal after 42 or 70 days, respectively. Time-to-peak tetanus tension was unchanged by muscle conditioning. Changes in the force-velocity relationship began after 3 days of stimulation, changed very little between 3 and 21 days of stimulation, and showed another change after 42 and 70 days of stimulation. It may be possible to better modify the muscle for dynamic cardiomyoplasty by pharmacological or stimulation regimens once the mechanism of fiber switching is better understood.

Transcriptional regulation of phospholamban gene and translational regulation of SERCA2 gene produces coordinate expression of these two sarcoplasmic reticulum proteins during skeletal muscle phenotype switching.

Chronic 1 Hz stimulation of the canine latissimus dorsi muscle produced a time-dependent switch from the fast-twitch to the slow-twitch phenotype. This included changes in the proteins of the sarcoplasmic reticulum. After 3 days of muscle stimulation, there was down-regulation of fast-twitch Ca-ATPase (SERCA1a) mRNA and induction of slow-twitch Ca-ATPase (SERCA2a) mRNA; most changes in both mRNAs were nearly complete after 14 days of stimulation. Although the induction of phospholamban mRNA began after 3 days of muscle stimulation, its up-regulation was not completed until the muscle had been stimulated for 42 days. The time course of expression of SERCA2a protein was very different from that of SERCA2a mRNA, suggesting that SERCA2 gene expression is regulated at the translational as well as the transcriptional level. The time course of expression of phospholamban protein closely followed that of phospholamban mRNA, suggesting that this gene is under transcriptional control. Thus coordinated expression of SERCA2a and phospholamban proteins is achieved via translational control of the SERCA2 gene and transcriptional control of the phospholamban gene.

A prospective study of "undiagnosed" isolated myelopathy: II. Value of magnetic resonance imaging, evoked potentials and CSF analysis.

We aimed to determine the sensitivity of available "diagnostic" tests in detecting subclinical abnormalities characteristic of multiple sclerosis (MS) in patients with unexplained isolated myelopathy, and any relationship between test results and level of disability. The trial investigations were carried out in 69 prospectively selected patients with acute or chronic noncompressive myelopathies. Magnetic resonance scans were the most sensitive individual tests, revealing asymptomatic brain lesions in 51 patients (74%, C.I. 64-84). An abnormal IgG/albumin ratio (IgG/A) was present in 29 (42%, C.I. 30-54), oligoclonal bands (OCB) in 27 (39%, C.I. 17-39) and abnormal evoked potentials (EP) (visual and/or auditory brain stem) in 19 cases (28%, C.I. 17-39). OCB and abnormal EP were found significantly less often than in control patients with clinically definite MS (CDMS) and significantly more often than in patients with myelopathy due to other conditions. The number of anatomical brain areas with lesions on magnetic resonance imaging (MRI) was significantly associated with CSF abnormalities; abnormal EP were correlated with abnormal MRI and elevated CSF immunoglobulins. Clinical classifications, age, symptom duration, disability levels and genetic factors did not appear to influence the prevalence of abnormal MRI or CSF. For the exclusion of compressive and structural diseases of the spinal cord, myelography has been superceded by cervical and thoracic MRI. In addition, MRI of the brain is the investigation of choice in patients with myelopathies that remain unexplained after spinal MRI. However, whether used alone or in combination with other tests, the specificity and predictive value of brain MRI abnormalities for the risk of developing MS, as well as the associated "false positive" rates, remain to be defined by long-term follow-up of prospectively ascertained and representative cases.