Leptomeningeal disease as a presenting feature of gestational trophoblastic neoplasia: A review and recommendations for management.

OBJECTIVES: Gestational Trophoblastic Neoplasia (GTN) is a rare group of malignant placental-related tumours requiring systemic anti-cancer treatment. Leptomeningeal disease (LMD) related to GTN is not well reported with no consensus in optimal treatment. We offer recommendations for management of these patients. METHODS: We discuss five patients with GTN who presented with features of LMD and were diagnosed with gadolinium-enhanced MRI brain, all of whom received low dose induction etoposide-cisplatin (EP) followed by either EP-etoposide, methotrexate (CNS) and actinomycin-D (EMA) or EMA(CNS)-cyclophosphamide and vincristine (CO). RESULTS: Four out of the five patients additionally received intrathecal methotrexate. Four patients had complete hCG response to first line multi-agent chemotherapy, one patient required second line paclitaxel, cisplatin alternating with paclitaxel, etoposide (TP/TE), where paclitaxel was substituted with nab-paclitaxel due to anaphylaxis, followed by hysterectomy. One of the four initial complete hCG responders relapsed in the lung requiring further systemic treatment with subsequent lobectomy. Patient reported outcomes indicate persistent neurological symptoms are mild and do not affect functionality and quality of life. CONCLUSION: With a follow-up range of 2-6 years, all five patients remain cured demonstrating excellent survival outcomes with the avoidance of whole-brain radiotherapy in all cases.

Nonlinear interactions in the thalamocortical loop in essential tremor: A model-based frequency domain analysis.

There is increasing evidence to suggest that essential tremor has a central origin. Different structures appear to be part of the central tremorogenic network, including the motor cortex, the thalamus and the cerebellum. Some studies using electroencephalogram (EEG) and magnetoencephalography (MEG) show linear association in the tremor frequency between the motor cortex and the contralateral tremor electromyography (EMG). Additionally, high thalamomuscular coherence is found with the use of thalamic local field potential (LFP) recordings and tremulous EMG in patients undergoing surgery for deep brain stimulation (DBS). Despite a well-established reciprocal anatomical connection between the thalamus and cortex, the functional association between the two structures during "tremor-on" periods remains elusive. Thalamic (Vim) LFPs, ipsilateral scalp EEG from the sensorimotor cortex and contralateral tremor arm EMG recordings were obtained from two patients with essential tremor who had undergone successful surgery for DBS. Coherence analysis shows a strong linear association between thalamic LFPs and contralateral tremor EMG, but the relationship between the EEG and the thalamus is much less clear. These measurements were then analyzed by constructing a novel parametric nonlinear autoregressive with exogenous input (NARX) model. This new approach uncovered two distinct and not overlapping frequency "channels" of communication between Vim thalamus and the ipsilateral motor cortex, defining robustly "tremor-on" versus "tremor-off" states. The associated estimated nonlinear time lags also showed non-overlapping values between the two states, with longer corticothalamic lags (exceeding 50ms) in the tremor active state, suggesting involvement of an indirect multisynaptic loop. The results reveal the importance of the nonlinear interactions between cortical and subcortical areas in the central motor network of essential tremor. This work is important because it demonstrates for the first time that in essential tremor the functional interrelationships between the cortex and thalamus should not be sought exclusively within individual frequencies but more importantly between cross-frequency nonlinear interactions. Should our results be successfully reproduced on a bigger cohort of patients with essential tremor, our approach could be used to create an on-demand closed-loop DBS device, able to automatically activate when the tremor is on.

Subarachnoid haemorrhage: an unusual complication of implantation of an intrathecal baclofen pump.

STUDY DESIGN: Single case-report. OBJECTIVES: To describe subarachnoid haemorrhage; an unusual complication following implantation of an intrathecal baclofen pump in an adult with spinal cord injury. SETTING: Princess Royal Spinal Injuries Unit, Sheffield, UK. METHODS: Review of the medical notes and literature. RESULTS: A 77-year-old man with an incomplete ASIA-C spinal cord injury at C5 level sustained 2 years previously, developed subarachnoid haemorrhage following implantation of an intrathecal baclofen pump for the management of spasticity that was unresponsive to treatment with oral antispasticity agents. CONCLUSION: Subarachnoid haemorrhage can occur as a rare complication of insertion of Intrathecal baclofen pump. This need to be considered while evaluating patients who present with headache, confusion and seizures in the post operative period. SPONSORSHIP: Not applicable.

Lymphoblastic leukaemia presenting as a carotid-cavernous fistula.

A carotid-cavernous fistula is a life-threatening condition characterised by an abnormal communication between the carotid arterial vessels and the cavernous venous system. Although these fistulae can arise spontaneously, they mainly occur after trauma, especially road traffic accidents, falls and penetrating cranial or orbital injuries. The mainstay of treatment involves endovascular embolization, but in those patients where this is not possible or where embolization fails, direct surgical intervention and ligation of the artery may be necessary. Here we describe an interesting case of a suspected carotid-cavernous fistula which turned out to be cavernous sinus syndrome secondary to lymphoma.

3.0 T MRI of 2000 consecutive patients with localisation-related epilepsy.

OBJECTIVES: Clinical guidelines suggest that all patients diagnosed with localised seizures should be investigated with MRI to identify any epileptogenic structural lesions, as these patients may benefit from surgical resection. There is growing impetus to use higher field strength scanners to image such patients, as some evidence suggests that they improve detection rates. We set out to review the detection rate of radiological abnormalities found by imaging patients with localised seizures using a high-resolution 3.0 T epilepsy protocol. METHODS: Data were reviewed from 2000 consecutive adult patients with localisation-related epilepsy referred between January 2005 and February 2011, and imaged at 3.0 T using a standard epilepsy protocol. RESULTS: An abnormality likely to be related to seizure activity was identified in 403/2000 (20.2%) patients, with mesial temporal sclerosis diagnosed in 211 patients. 313/2000 (15.6%) had lesions potentially amenable to surgery. Abnormalities thought unrelated to seizure activity were found in 324/2000 (16.1%), with 8.9% having evidence of ischaemic disease. CONCLUSIONS: Since the introduction of the then National Institute for Clinical Excellence guidelines in 2004, the detection rate of significant pathology using a dedicated 3.0 T epilepsy protocol has not fallen, despite the increased numbers of patients being imaged. This is the largest study of epilepsy imaging at 3.0 T to date and highlights the detection rates of significant pathology in a clinical setting using a high-strength magnet. The prevalence of ischaemic disease in this population is significantly higher than first thought, and may not be incidental, as is often reported.

The Anatomy of the Medial Lemniscus within the Brainstem Demonstrated at 3 Tesla with High Resolution Fat Suppressed T1-Weighted Images and Diffusion Tensor Imaging.

The medial lemniscus is part of the main somatosensory pathways ascending within the brainstem. It is formed by the heavily myelinated axons of the second order neurones of the dorsal column nuclei. This pathway ascends through the rostral medulla, pons and mesencephalon to finally terminate by synapsing with third order neurones in the ventral posterior nucleus of the thalamus. The medial lemniscus conveys proprioception and fine tactile discrimination as part of the somatosensory system. Conventional MRI studies of the brainstem have been relatively poor in demonstrating these fibre pathways. Diffusion tensor imaging and tractography may demostrated fibre pathways in the brainstem. These techniques do however suffer from relatively poor spatial resolution and some degree of image distortion - especially if based on echo planar imaging techniques. Knowledge of the anatomical relationships of the medial lemniscus is important for the understanding of clinical manifestations of disease processes affecting the somatosensory pathways and also to demonstrate important adjacent structures. Specifically, the pedunculopontine nucleus (PPN) lies in close anatomical relationship to the medial lemniscus and the decussation of the superior cerebellar peduncle. This nucleus is a promising target for deep brain stimulator placement for alleviation of non-dopamine responsive dystonias. Six healthy male volunteers (mean age 33 years) were imaged at 3 Tesla. Imaging protocols consisted of thin section, high resolution, fat suppressed T1-weighted sequences as well as thin section, high isotropic resolution diffusion tensor imaging (DTI), which was analysed to generate colour fractional anisotropy (FA) maps. These were correlated with the fat suppressed T1 weighted images. In all volunteers the medial lemniscus was seen as a pair of bands of low signal on axial, high resolution, fat suppressed T1-weighted images. They were indentified through the upper medulla, pons and mesencephalon. They correlated well with the head to foot orientated fibres on the colour FA maps generated from the DTI data. This study of normal volunteers has illustrated the value of high resolution, fat suppressed T1-weighted images in demonstrating the anatomy of the heavily myelinated medial lemniscus within the brainstem. These high resolution images with good spatial accuracy can potentially be used to aid the localisation of other nuclei, such as the PPN.

Spontaneous closure of a type 2a dural arteriovenous fistula following late recanalization of the occluded sinus.

We describe the rare spontaneous resolution of a type 2a dural AVF that coincided with recanalization of the previously thrombosed sigmoid sinus after ten years of conservative management. The factors potentially responsible for spontaneous fistula obliteration are discussed and the therapeutic implication of this observation is considered.

Investigating the 'latent' deficit hypothesis: age at time of head injury, implicit and executive functions and behavioral insight.

This study investigated the 'latent deficit' hypothesis in two groups of head-injured patients with predominantly frontal lesions, those injured prior to steep morphological and corresponding functional maturational periods for frontal networks (28 years. The latent deficit hypothesis proposes that early injuries produce enduring cognitive deficits manifest later in the lifespan with graver consequences for behavior than adult injuries, particularly after frontal pathology (Eslinger, Grattan, Damasio & Damasio, 1992). Implicit and executive deficits both contribute to behavioral insight after frontal head injury (Barker, Andrade, Romanowski, Morton, & Wasti, 2006). On the basis of morphological and behavioral data, we hypothesized that early injury would confer greater vulnerability to impairment on tasks associated with frontal regions than later injury. Patients completed experimental tasks of implicit cognition, executive function measures and the DEX measure of behavioral insight (Behavioral Assessment of the Dysexecutive Syndrome: Wilson, Alderman, Burgess, Emslie, & Evans, 1996). The Early Injury group were more impaired on implicit cognition tasks compared to controls that Late Injury patients. There were no marked group differences on most executive function measures. Executive ability only contributed to behavioral awareness in the Early Injury Group. Findings showed that age at injury moderates the relationship between executive and implicit cognition and behavioral insight and that early injuries result in long-standing deficits to functions associated with frontal regions partially supporting the latent deficit hypothesis.

Neurolinguistic programming used to reduce the need for anaesthesia in claustrophobic patients undergoing MRI.

The purpose of this study was to assess the success of neurolinguistic programming in reducing the need for general anaesthesia in claustrophobic patients who require MRI and to consider the financial implications for health providers. This was a prospective study performed in 2006 and 2007 at a teaching hospital in England and comprised 50 adults who had unsuccessful MR examinations because of claustrophobia. The main outcome measures were the ability to tolerate a successful MR examination after neurolinguistic programming, the reduction of median anxiety scores produced by neurolinguistic programming, and models of costs for various imaging pathways. Neurolinguistic programming allowed 38/50 people (76%) to complete the MR examination successfully. Overall, the median anxiety score was significantly reduced following the session of neurolinguistic programming. In conclusion, neurolinguistic programming reduced anxiety and subsequently allowed MRI to be performed without resorting to general anaesthesia in a high proportion of claustrophobic adults. If these results are reproducible, there will be major advantages in terms of patient safety and costs.

The value of radio-anatomical features on non-contrast CT scans in localizing the source in aneurysmal subarachnoid haemorrhage.

Identification of the source of subarachnoid haemorrhage (SAH) can be a challenge in the presence of multiple aneurysms. This study was carried out to assess whether radioanatomical features on noncontrast enhanced computerised tomography (CT) scans may be of value in localizing ruptured intracranial aneurysms. The diagnostic CT scans of 56 consecutive patients, investigated for SAH with cerebral angiography, over a period of six months were available for review. Various radioanatomical features were assessed: (1) pattern of subarachnoid blood (e.g. predominant site and location near major vessel bifurcation), (2) presence of intraparenchymal haematoma, (3) presence of aneurysm contour and (4) hydrocephalus. On the basis of the findings an estimation of the anatomical location of the source of bleeding was made and then compared with the angiogram findings to which the reviewer was blinded. The location of the aneurysm was correctly identified in 89.5% of cases. Careful analysis of the pattern of bleeding was essential for the successful localization of the aneurysm in all these cases. The presence of an aneurysm contour was also associated with correct identification of the source of bleeding (chi(2) = 6.067, P = 0.02). Our findings suggest that radioanatomical features on CT scans in SAH can be a valuable aid in the correct identification of the location of the ruptured aneurysm. This would be of particular significance in the presence of multiple intracranial aneurysms.

Complications of cerebral angiography: a prospective analysis of 2,924 consecutive procedures.

INTRODUCTION: Cerebral angiography is an invasive procedure associated with a small, but definite risk of neurological morbidity. In this study we sought to establish the nature and rate of complications at our institution among a large prospective cohort of consecutive patients. Also, the data were analysed in an attempt to identify risk factors for complications associated with catheter angiography. METHODS: Data were prospectively collected for a consecutive cohort of patients undergoing diagnostic cerebral angiography between January 2001 and May 2006. A total of 2,924 diagnostic cerebral angiography procedures were performed during this period. The following data were recorded for each procedure: date of procedure, patient age and sex, clinical indication, referring specialty, referral status (routine/emergency), operator, angiographic findings, and the nature of any clinical complication or asymptomatic adverse event (arterial dissection). RESULTS: Clinical complications occurred in 23 (0.79%) of the angiographic procedures: 12 (0.41%) significant puncture-site haematomas, 10 (0.34%) transient neurological events, and 1 nonfatal reaction to contrast agent. There were no permanent neurological complications. Asymptomatic technical complications occurred in 13 (0.44%) of the angiographic procedures: 3 groin dissections and 10 dissections of the cervical vessels. No patient with a neck dissection suffered an immediate or delayed stroke. Emergency procedures (P = 0.0004) and angiography procedures performed for intracerebral haemorrhage (P = 0.02) and subarachnoid haemorrhage (P = 0.04) were associated with an increased risk of complications. CONCLUSION: Neurological complications following cerebral angiography are rare (0.34%), but must be minimized by careful case selection and the prudent use of alternative noninvasive angiographic techniques, particularly in the acute setting. The low complication rate in this series was largely due to the favourable case mix.

Proton spectroscopy and imaging at 3T in ataxia-telangiectasia.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with characteristic neurodegeneration of the cerebellum. We used MR spectroscopy to test the hypothesis that cerebellar metabolism in A-T patients would be abnormal relative to healthy controls. METHODS: Twelve adults with A-T and 12 healthy control subjects underwent MR imaging and long-echo time (1)H-MR spectroscopy at 3T. Voxels were acquired in the region of the dentate nucleus of the cerebellum and in parietooccipital white matter, and ratios for N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were calculated. RESULTS: All of the A-T patients showed marked cerebellar atrophy of the vermis and hemispheres. Two patients showed multiple small foci of hypointensity on T2*-weighted images throughout their brain suggestive of capillary telangiectasia. A further 2 patients had single low-signal-intensity foci. One patient had a tumor, thought to be meningioma radiologically, that was not suspected clinically. No group differences were found in the cerebral spectra, but analysis of the cerebellum revealed significantly lower NAA/Cho and higher Cho/Cr ratios in the A-T patients compared with the controls. There was no difference between groups for the NAA/Cr ratio. CONCLUSION: The findings suggest increased Cho signal intensity in the cerebellum of adult A-T patients. If this finding is shown through the course of the disease, it may assist in the differentiation of early A-T from other forms of ataxia and provide a marker for monitoring treatment efficacy.

Implicit cognition is impaired and dissociable in a head-injured group with executive deficits.

Implicit or non-conscious cognition is traditionally assumed to be robust to pathology but Gomez-Beldarrain et al. recently showed deficits on a single implicit task after head injury. Laboratory research suggests that implicit processes dissociate. This study therefore examined implicit cognition in 20 head-injured patients and age- and IQ-matched controls using a battery of four implicit cognition tasks: a serial reaction time task (SRT), mere exposure effect task, automatic stereotype activation and hidden co-variation detection. Patients were assessed on an extensive neuropsychological battery, and MRI scanned. Inclusion criteria included impairment on at least one measure of executive function. The patient group was impaired relative to the control group on all the implicit cognition tasks except automatic stereotype activation. Effect size analyses using the control mean and standard deviation for reference showed further dissociations across patients and across implicit tasks. Patients impaired on implicit tasks had more cognitive deficits overall than those unimpaired, and a larger dysexecutive self/other discrepancy (DEX) score suggesting greater behavioural problems. Performance on the SRT task correlated with a composite measure of executive function. Head injury thus produced heterogeneous impairments in the implicit acquisition of new information. Implicit activation of existing knowledge structures appeared intact. Impairments in implicit cognition and executive function may interact to produce dysfunctional behaviour after head injury. Future comparisons of implicit and explicit cognition should use several measures of each function, to ensure that they measure the latent variable of interest.

Imaging findings and referral outcomes of rapid assessment stroke clinics.

AIM: A rapid assessment stroke clinic (RASC) was established to provide a rapid diagnostic service to individuals with suspected transient cerebral or ocular ischaemia or recovered non-hospitalized strokes. In this report we review imaging findings and clinical outcomes of patients proceeding to the carotid surgery programme. METHODS: Between October 2000 and December 2002, 1339 people attended the RASC. The findings of head CT and carotid Doppler ultrasound of the 1320 patients who underwent brain and carotid imaging were reviewed, and the number subsequently proceeding to carotid angiography and intervention was reported. RESULTS: CT head scans were normal in 57% of cases; 38% demonstrated ischaemia or infarction; and 3% yielded incidental or other significant findings not related to ischaemia. On screening with carotid Doppler ultrasound, 7.5% showed greater than 50% stenosis on the symptomatic side. A total of 83 patients (6.2%) proceeded to cerebral angiography and 65 (4.8%) underwent carotid endarterectomy or endovascular repair. CONCLUSION: Rapid-access neurovascular clinics are efficient in selecting patients for carotid intervention, but this is at a cost and the number of potential strokes prevented is small. Alternative management pathways based on immediate medical treatment need to be evaluated.

MR imaging of patients with localisation-related seizures: initial experience at 3.0T and relevance to the NICE guidelines.

The purpose of this study is to describe our initial experience of imaging adults with localisation-related epilepsy using MR imaging at 3.0T. We discuss the findings in the context of the recently released NICE guidelines that provide detailed advice on imaging people with epilepsy in the UK. 120 consecutive people over the age of 16 years with localisation-related epilepsy were referred for clinical MR examinations from a regional neuroscience centre in England. None of the people had had MR examinations prior to the present study. High resolution MR imaging was performed taking advantage of the high field strength and high performance gradients of the system. Two experienced neuroradiologists reported on the examinations independently and the presence and type of pathology was recorded. There was complete agreement between the two reporters in all 120 cases. The overall frequency of abnormalities shown by MR was 31/120 (26%) and the commonest abnormality shown was mesial temporal sclerosis found in 10/120 (8%). Tumours were shown in 4/120, all of which appeared low grade as judged by imaging criteria. Epilepsy is the commonest neurological condition and demands a significant resource in order to provide good care for sufferers. Recent guidelines published in the UK have suggested that the majority of people with epilepsy should receive brain MR as part of their routine assessment. Our work shows that using the most sophisticated MR imaging in a highly selected population there is a modest pick-up rate of brain abnormalities. If a widespread epilepsy-imaging programme is started the detection rate is likely to be much lower. Although MR is acknowledged to be a reliable way of detecting pathology in people with epilepsy there is a dearth of information studying the health economics of imaging epilepsy in relation to patient management and outcomes.

Disconnection agraphia in a case of multiple sclerosis: the isolation of letter movement plans from language.

We report the case of a left-handed man (MCR), who presented with a peripheral agraphia as an early sign of multiple sclerosis. His left-handed writing was neologistic, whilst oral spelling, typing and spelling with the right hand were intact. Structural MRI scanning revealed a lesion of the body of the corpus callosum. Dichotic listening tests indicated that MCR displayed left hemisphere dominance for language. It is proposed that MCR represents a case of a disconnection syndrome in which right hemisphere systems that provide the basis for movement templates during left-handed writing are isolated from left hemisphere language systems. Analysis of left-handed writing indicated that peripheral movement control was highly structured with both individual letter frequency and sequential dependencies between letters represented within these motor control units. This case represents an opportunity to explore the mechanisms of movement control for writing and to examine the characteristics of isolated letter templates.

Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS.

BACKGROUND: High angular resolution diffusion tensor imaging (HARD) is an MRI technique that exploits the mobility of water molecules to yield maps of structural order and directionality of white matter tracts with greater precision than six-direction diffusion tensor imaging (DTI) schemes. OBJECTIVE: To assess whether HARD is more sensitive than conventional MRI or neurologic assessment in detecting the upper motor neuron (UMN) pathology of patients with ALS. METHODS: Twenty-five patients with definite UMN clinical signs and 23 healthy volunteers underwent conventional MRI. HARD datasets were collected from a subset of these participants plus four patients with isolated lower motor neuron (LMN) signs. ALS symptom severity was assessed by a neurologist, the conventional MR images were reviewed by neuroradiologists, and the DTI maps were subject to quantitative region of interest analysis. RESULTS: Motor cortex hypointensity on T2-weighted images and corona radiata hyperintensity on proton density-weighted images distinguished patients with UMN involvement from volunteers with 100% specificity, but only 20% sensitivity. Fractional anisotropy (FA) was reduced in the posterior limb of the internal capsule in patients with UMN involvement compared to volunteers. A FA threshold value with a sensitivity of 95% to detect patients with ALS (including those with isolated LMN signs) had a specificity of 71%. CONCLUSIONS: High angular resolution diffusion tensor imaging may be more sensitive than conventional MRI or neurologic assessment to the upper motor neuron (UMN) pathology of ALS, but it lacks the specificity required of a diagnostic marker. Instead, it is potentially useful as a quantitative tool for monitoring the progression of UMN pathology.