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.

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.

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.

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.

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.

Aneurysmal SAH: cognitive outcome and structural damage after clipping or coiling.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) and surgical clipping of intracranial aneurysms are associated with substantial morbidity and mortality. OBJECTIVE: To compare cognitive outcome and structural damage in patients with aneurysmal SAH treated with surgical clipping or endovascular coiling. METHODS: Forty case-matched pairs of patients with aneurysmal SAH treated by surgical clipping or endovascular coiling were prospectively assessed by use of a battery of cognitive tests. Twenty-three case-matched pairs underwent MRI 1 year after the procedure. Matching was based on grade of SAH on admission, location of aneurysm, age, and premorbid IQ. RESULTS: Both groups were impaired in all cognitive domains when compared with age-matched healthy control subjects. Comparison of cognitive outcome between the two groups indicated an overall trend toward a poorer cognitive outcome in the surgical group, which achieved significance in four tests. MRI showed focal encephalomalacia exclusively in the surgical group. This group also had a significantly higher incidence of single or multiple small infarcts within the vascular territory of the aneurysm, but both groups had similar incidence of large infarcts and global ischemic damage. CONCLUSION: Endovascular treatment may cause less structural brain damage than surgery and have a more favorable cognitive outcome. However, cognitive outcome appears to be dictated primarily by the complications of SAH.

Brain arteriovenous malformations: assessment with dynamic MR digital subtraction angiography.

BACKGROUND AND PURPOSE: Conventional catheter angiography (CCA) is the current reference standard for the diagnosis, assessment, and management of pial brain arteriovenous malformations (AVMs). The purpose of this study was to develop an MR angiographic technique that produces dynamic images comparable to those provided by CCA and to apply the technique to the investigation of pial brain AVMs. METHODS: Twenty patients with brain AVMs referred for stereotactic radiosurgery were recruited. All patients had CCA performed on a 1.5-T superconducting system. Sixty images were obtained at a rate of one image per second. Slices were orientated to produce Towne, lateral, and anteroposterior projections. A set of mask images was taken and then a series during the passage of a bolus of contrast material. MR examinations were assessed independently by neuroradiologists blinded to the conventional catheter angiographic findings. RESULTS: The nidus of the AVMs was depicted in 19 of the 20 patients, and correlation with CCA was excellent for measurements of maximum diameter. Venous drainage was correctly assessed in 18 of 19 cases. CONCLUSION: MR digital subtraction angiography shows promise as a noninvasive, dynamic angiographic tool for planning stereotactic radiosurgery of AVMs already delineated by catheter angiography. At present, it suffers from temporal and spatial resolution, which impede the assessment of some brain AVMs.

Multimodality MR imaging depiction of hemodynamic changes and cerebral ischemia in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a common and serious neurologic emergent condition. We tested the hypothesis that multimodality MR imaging depicts changes in cerebral blood flow SAH, before any surgical or endovascular intervention, and that the frequency of these changes increases with time after ictus. METHODS: We prospectively examined 37 patients with suspected SAH and three with symptoms of acute stroke but who subsequently had SAH. Routine CT and multimodality MR imaging were performed within 18 h of presentation. Standard MR imaging, diffusion-weighted MR imaging, time-of-flight MR angiography, and dynamic first-pass gadolinium-enhanced MR perfusion imaging were performed. Images were reviewed for abnormalities in cerebral blood flow, ischemia, and infarction. Nine patients did not have SAH at CT and CSF investigations. Of 31 patients with proved SAH, 13 were examined during the acute stage (within 4 d of ictus) and 18, during the subacute stage (4-14 d after ictus). RESULTS: MR imaging showed alteration in cerebral blood flow parameters in 16 of 31 patients before surgery or endovascular treatment. The frequency of blood flow changes and associated complications increased with worsening clinical grade and increasing time after ictus. CONCLUSION: Multimodality MR imaging provides information not available from CT in patients with SAH. MR imaging shows oligemic and ischemic areas in SAH before surgery or endovascular treatment. MR imaging is a simple noninvasive method of assessing cerebral blood flow and its complications in SAH. It can be performed in a clinical environment.

Reduction of radiation doses in leg lengthening procedures by means of audit and computed tomography scanogram techniques.

Children with congenital bone dysplasias may benefit from leg lengthening procedures. Such procedures, by necessity, require frequent and regular imaging. It is necessary to minimize the total radiation dose to these patients, and particularly the dose to the gonads. In the present study the films of 13 patients who had completed leg lengthening procedures were reviewed. The number of films was assessed together with the use of appropriate gonad shielding. In a second part of the study, thermoluminescent dosemeter measurements of radiation doses to a phantom were made for both plain radiographs (with and without gonad protection) and computed tomography (CT) scanograms. The results show that audit plays an important role in assessing radiographic practice with respect to accurate placement of gonad protection and confirm that a significant dose reduction can be accomplished by careful use of this lead shielding. Dose reduction can also be achieved by using alternative radiographic techniques such as CT scanograms. Other techniques such as ultrasound or dual-energy X-ray absorptiometry are briefly discussed. These may play an important additional part in the reduction of total radiation dose to the patients.

Motor functional MRI for pre-operative and intraoperative neurosurgical guidance.

Functional MRI (fMRI) may provide a means of locating areas of eloquent cortex that can be used to guide neurosurgeons in their quest to maximize intracerebral tumour resection whilst minimizing post-procedural neurological deficits. This work aimed to develop and provide an initial assessment of such a technique. 19 patients with mass lesions close to the primary motor cortex underwent fMRI at 1.5T. A single shot echo planar technique was used to acquire data corresponding to right and left hand movement. Resultant activation maps were used to aid pre-surgical planning. Data was used in conjunction with an intraoperative navigation system in 13 cases. Activation was attributed to primary motor, primary somatosensory or supplementary motor cortex in 17 of 19 subjects. No permanent changes in motor deficit were detected post surgery. The additional information provided by fMRI, particularly when incorporated into a neuronavigation guided craniotomy, was deemed highly valuable to the neurosurgeon as it enabled safe resection of tumour in anatomical locations previously deemed to be too high risk for safe resection using conventional (non-fMRI-guided) technique. This observation is reinforced by the fact that no patients suffered permanent neurological deficit after radical tumour debulking (surgical estimates >90% tumour resection).

Subcortical hypoperfusion following surgery for aneurysmal subarachnoid haemorrhage: implications for cognitive performance?

The incidence and severity of cognitive deficits after surgery for aneurysmal subarachnoid haemorrhage and their relationship to aneurysm site remains controversial. The aim of this study was to investigate the pattern of regional cerebral blood flow which exists in patients one year post-surgery and to identify whether different patterns exist which may be related to the type of cognitive deficit or the location of the aneurysm. 62 patients underwent cognitive assessment and HMPAO SPECT imaging at a mean time of 12 months following surgery. Results were compared to those from healthy control subjects (n = 55 for neuropsychological testing; n = 14 for SPECT imaging). In the patient group, significant stable cognitive deficits occurred in all cognitive domains but no cognitive measure differentiated aneurysm site. On SPECT images, statistical parametric mapping identified a large common area of subcortical hypoperfusion in the patient group as a whole. The findings of this study suggest a possible link between reduced subcortical function and the extent and severity of cognitive deficits.

Spontaneous intracranial hypotension--lessons to be learned for the investigation of post dural puncture headache.

We describe a case of spontaneous intracranial hypotension in a 36-year-old woman. This condition shares many of the features of post dural puncture headache, but without a dural puncture having been performed. The aetiology and management of this rare condition are discussed. We believe from experience within our own unit that most anaesthetists are unaware of spontaneous intracranial hypotension. Highlighting this condition is important, as anaesthetists are often involved in its management. In our case, radiological investigation involved the use of spiral computerised tomography to identify the site of the hole in the dura. Spiral computerised tomography is a relatively recent innovation, which may also be useful in the investigation of post dural puncture headache when the level of the puncture is unknown.

Neurofibromatosis types I and II: radiological appearance.

The neurocutaneous disorders frequently involve the central nervous system. This, the first in a pair of articles which describe and illustrate the radiological appearances of the central nervous system manifestations of the most common neurocutaneous disorders, looks at neurofibromatosis types I and II.

Tuberous sclerosis, von Hippel-Lindau disease, Sturge-Weber syndrome.

The neurocutaneous disorders frequently involve the central nervous system. This is the second in a pair of articles describing and illustrating the radiological appearances of the central nervous system manifestations of these disorders, this article looking at tuberous sclerosis, von Hippel-Lindau disease and Sturge-Weber syndrome.

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.