MRI differential diagnosis of suspected multiple sclerosis.

Diagnosing multiple sclerosis (MS) can be very challenging owing to its variable clinical features and lack of a definitive test. Magnetic resonance imaging (MRI) is a core diagnostic tool in the detection of MS lesions and demonstration of spatial and temporal distribution of disease. Moreover, MRI plays a crucial role in the exclusion of alternative diagnoses of MS. The aim of this review is to describe the typical MRI features of MS and to present a series of common mimics of MS with emphasis on their distinguishing features from MS.

A de novo frameshift in HNRNPK causing a Kabuki-like syndrome with nodular heterotopia.

Kabuki syndrome is a heterogeneous condition characterized by distinctive facial features, intellectual disability, growth retardation, skeletal abnormalities and a range of organ malformations. Although at least two major causative genes have been identified, these do not explain all cases. Here we describe a patient with a complex Kabuki-like syndrome that included nodular heterotopia, in whom testing for several single-gene disorders had proved negative. Exome sequencing uncovered a de novo c.931_932insTT variant in HNRNPK (heterogeneous nuclear ribonucleoprotein K). Although this variant was identified in March 2012, its clinical relevance could only be confirmed following the August 2015 publication of two cases with HNRNPK mutations and an overlapping phenotype that included intellectual disability, distinctive facial dysmorphism and skeletal/connective tissue abnormalities. Whilst we had attempted (unsuccessfully) to identify additional cases through existing collaborators, the two published cases were 'matched' using GeneMatcher, a web-based tool for connecting researchers and clinicians working on identical genes. Our report therefore exemplifies the importance of such online tools in clinical genetics research and the benefits of periodically reviewing cases with variants of unproven significance. Our study also suggests that loss of function variants in HNRNPK should be considered as a molecular basis for patients with Kabuki-like syndrome.

Role of radiology in central nervous system stimulation.

Central nervous system (CNS) stimulation is becoming increasingly prevalent. Deep brain stimulation (DBS) has been proven to be an invaluable treatment for movement disorders and is also useful in many other neurological conditions refractory to medical treatment, such as chronic pain and epilepsy. Neuroimaging plays an important role in operative planning, target localization and post-operative follow-up. The use of imaging in determining the underlying mechanisms of DBS is increasing, and the dependence on imaging is likely to expand as deep brain targeting becomes more refined. This article will address the expanding role of radiology and highlight issues, including MRI safety concerns, that radiologists may encounter when confronted with a patient with CNS stimulation equipment in situ.

CNS effects following the treatment of malignancy.

Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes.

Magnetic resonance imaging of acute intramedullary myelopathy: radiological differential diagnosis for the on-call radiologist.

Spinal cord disease is often viewed as having a poor outcome. Although in certain conditions this is true, non-traumatic myelopathy encompasses a vast array of diseases some of which are exquisitely responsive to treatment. Accurate diagnosis becomes important as damage is often progressive and long-term disability and morbidity is related to the degree of neurological impairment when the diagnosis is reached. Out-of-hours magnetic resonance imaging (MRI) is generally requested and performed to ascertain whether there is spinal cord compression; however, there are other causes of a cord syndrome, which are more subtle. This review aims to provide a summary of the imaging features of non-traumatic intramedullary spinal cord emergencies, many of which may appear radiologically similar.

White matter changes in Leber's hereditary optic neuropathy: MRI findings.

Leber's hereditary optic neuropathy is a mitochondrial disorder causing bilateral optic nerve degeneration. It is sometimes associated with clinical signs of multiple sclerosis. We report MRI findings in two patients with LHON-MS and comment on possible distinguishing features of this disease entity.

Calvarial masses of infants and children. A radiological approach.

Children frequently present with asymptomatic head lumps that have been discovered by their parents or by their hairdressers. Other children present with painful lumps or symptoms of intra-cranial masses with calvarial involvement. Imaging plays an important role in the diagnosis of such masses and in subsequent surgical planning. We present a review of the types of lesion that may present in these ways.

The role of MRI in the diagnosis of MS.

Magnetic resonance imaging (MRI) is the most widely used imaging technique in the investigation of multiple sclerosis (MS). Although MS remains a clinical diagnosis, MRI has become an invaluable tool in understanding and monitoring the disease, and is commonly used to confirm the clinical diagnosis. Various imaging techniques can be used but T2-weighted brain imaging remains the standard tool. The officially endorsed imaging criteria for MS places greater emphasis on the spatial and temporal distribution of lesions than on their individual appearance. This review focuses on the more typical findings in MS, and considers the current role of MRI in the diagnosis.

Intra-cranial manifestations of the neurocutaneous syndromes.

The neurocutaneous syndromes or phakomatoses are a heterogeneous group of congenital disorders primarily involving structures derived from the embryological neuroectoderm. All of the syndromes involve the central nervous system (CNS). Peripheral nerves, skin and other organ systems may also be involved. Twenty to 30 disorders are now classified as neurocutaneous syndromes. This article reviews the intra-cranial imaging features of some of the commonest.

Neuropsychological deficits in multiple sclerosis after acute relapse.

OBJECTIVES: To examine cognitive and neurological changes and their relation to brain pathology in patients with multiple sclerosis during acute relapse. METHODS: Thirteen patients with multiple sclerosis were examined with a battery of neuropsychological tests during acute relapse and six weeks later. Their performance was compared with the performance of 10 controls matched for age and premorbid IQ. Gadolinium (Gd) enhanced MRI was also performed in patients on both occasions. RESULTS: The patients with multiple sclerosis performed significantly worse than controls on most tests of attention and memory during acute relapse and in remission. At follow up there was a significant or trend of improvement in performance on some tests of attention for patients in whom the Gd enhanced lesion load had decreased. In this subgroup of patients, their improvement also correlated significantly with the reduction in acute lesion load. CONCLUSIONS: The findings suggest that certain neuropsychological deficits detected during an acute relapse may be reversible, particularly in patients who initially have mild cognitive impairment.

Radiologists and visual acuity.

Visual acuity (VA) and potential risks to the radiologist's eyesight have been relatively neglected subjects in the radiological literature. This study comprises two parts, the first consisting of a questionnaire on this subject sent to a random sample of 480 practising radiologists in the United Kingdom, and the second, a spot check of the VA of radiologists in our department. Of questionnaires, 73 %were returned. Of respondents, 76 % felt that ionising radiation could affect their vision, but only 13 % used lead glasses on a regular basis. A total of 71 % felt that regular monitoring of eyesight should be required. Of 25 tested radiologists, 5 had suboptimal VA and could benefit from further correction. The pertinent literature is reviewed, and a case for periodic eyesight testing is presented, including VA and grey-scale discrimination.

Executive function in multiple sclerosis. The role of frontal lobe pathology.

Deficits in executive function and the relationship to frontal lesion load as detected on MRI were investigated in 42 multiple sclerosis patients. A battery of neuropsychological test examining executive skills including computerized tests of planning and spatial working memory was administered to all subjects. Performance on these tests was impaired in the patient group when compared with a group of matched controls, but not all executive skills were affected to the same extent. Although a number of executive test scores correlated with the severity of frontal lesion load, it was difficult to disentangle the specific contribution of frontal lobe pathology to the impairment on executive tasks. This study highlights the difficulties in attempting to attribute specific cognitive abnormalities to focal brain pathology in the presence of widespread disease such as in multiple sclerosis.

MRI in children receiving total parenteral nutrition.

Cranial MRI was obtained in 13 of a group of 57 children receiving long-term parenteral nutrition, who were being investigated for hypermanganasaemia. Increased signal intensity on T1-weighted images has been reported in adult patients on long-term parenteral nutrition and with encephalopathy following chronic manganese exposure in are welding. It has been postulated that these changes are due to deposition of the paramagnetic trace element manganese. In excess manganese is hepato- and neurotoxic and we present the correlation of whole blood manganese levels with imaging findings. The age range of our patients was 6 months to 10 years, and the duration of therapy 3 months to 10 years. In 7 children we found characteristic increased signal intensity on T1-weighted images, with no abnormality on T2-weighted images. All patients had elevated whole blood manganese levels, suggesting that the basis for this abnormality is indeed deposition of manganese within the tissues.

Manganese toxicity in children receiving long-term parenteral nutrition.

BACKGROUND: In patients receiving long-term parenteral nutrition (PN), cholestatic disease and nervous system disorders have been associated with high blood concentrations of manganese. In such patients, the normal homoeostatic mechanisms of the liver and gut are bypassed and the requirement for this trace element is not known; nor has it been certain whether hypermanganesaemia causes the cholestasis or vice versa. We explored the direction of effect by serial tests of liver function after withdrawal of manganese supplements from children receiving long-term PN. We also examined the relation between blood manganese concentrations and brain lesions, as indicated by clinical examination and magnetic resonance imaging (MRI). METHODS: From a combined group of 57 children receiving PN we identified 11 with the combination of hypermanganesaemia and cholestasis; one also had a movement disorder. Manganese supplements were reduced in the first three and withdrawn in the remainder. MRI was done in two of these children. We also looked at manganese concentrations and MRI scans in six children who had received PN for more than 2 years without developing liver disease. FINDINGS: In the hypermanganesaemia/cholestasis group, four of the 11 patients died. In the seven survivors baseline whole-blood manganese was 615-1840 nmol/L, and after 4 months it had declined by a median of 643 nmol/L (p < 0.01). Over the same interval total bilirubin declined by a median of 70 mumol/L (p < 0.05). Two of these children had movement disorders, one of whom survived to have an MRI scan; this showed, with T1 weighted images, bilateral symmetrically increased signal intensity in the globus pallidus and subthalamic nuclei. Such changes were also seen in five other children--one from the hypermanganesaemia/cholestasis group and four of six in the long-term PN group without liver disease (in all of whom blood manganese was above normal). INTERPRETATION: The cholestasis complicating PN is multifactorial, but these results add to the evidence that manganese contributes. In view of the additional hazard of basal ganglia damage from high manganese levels in children receiving long-term PN, we recommend a low dose regimen of not more than 0.018 mumol/kg per 24 h together with regular examination of the nervous system.

The incidence and relevance of bone sclerosis in orbital pseudotumour.

We reviewed the CT studies of 176 patients with biopsy-proven inflammatory pseudotumour of the orbit, in an attempt to establish the incidence of bone sclerosis in this condition. We found 20 patients (11.5%) to show definite bone sclerosis and/or hyperostosis, and in a further 10 (6%) there was probable sclerosis, giving a total of 30 patients (17%) with some evidence of bony change. Bone-window films were available for a minority of patients, and the frequency of sclerosis was therefore probably underestimated. This feature, which presumably represents a low-grade, chronic sterile osteitis, has not previously been emphasised.

The upper airway and sleep apnoea in the Prader-Willi syndrome.

Obesity, short stature, hypotonia and excessive daytime sleepiness are characteristic features of the Prader-Willi syndrome. Excessive daytime sleepiness has been attributed to obstructive sleep apnoea (OSA). To investigate the role of anatomical factors in OSA in the Prader-Willi syndrome, clinical and ENT assessment, radiology of the upper airway and polysomnography including sleep oximetry were done in 14 subjects. Excessive daytime sleepiness was present in eight of 14 subjects as determined by a mean sleep latency to non-rapid eye movement stage I-II of < 5 min and/or self-rating sleepiness score > 9 (Epworth Sleepiness scale). Seven subjects were snorers or mouth breathers and dental abnormalities were present in 11. Sleep apnoea, as determined by a combined apnoea-hypopnoea index of more than 10 respiratory events per hour was present in 12 of 14 subjects. On clinical assessment, the nasopharynx, oropharynx and hypopharynx were small in one subject. No subject had redundant pharyngeal mucosa or an enlarged tongue. However, radiological studies performed in the awake supine posture showed a slight reduction in the cross-sectional area in nine subjects at the oropharyngeal level and in four subjects at the nasopharyngeal level as compared with normal control subjects. Sleep apnoea and minor radiological evidence of narrowing of the upper airway are common in the Prader-Willi syndrome, although clinical otolaryngological examination is often unremarkable. Excessive daytime sleepiness occurs in approximately 50% of all patients with Prader-Willi syndrome. Although obstructive sleep apnoea is one important factor related to sleepiness, an additional central disturbance of sleep mechanisms is present.