'Insulin neuritis' to 'treatment-induced neuropathy of diabetes': new name, same mystery.

Insulin neuritis is a historical term for an acute neuropathy affecting patients with diabetes who achieve rapid re-establishment of previously poor glycaemic control. It presents with neuropathic pain, symptoms of autonomic dysfunction or a combination of both. Recently, it has been proposed that 'treatment-induced neuropathy of diabetes' would be a more accurate name for this entity. The management focuses on controlling the symptoms while they gradually improve with time.

Anti-N-methyl-D-aspartate receptor antibodies: a potentially treatable cause of encephalitis in the intensive care unit.

OBJECTIVE: To report the occurrence of an unusual neurologic disorder requiring admission to the intensive care unit. DESIGN: Analysis of an observational cohort study of 31 patients with encephalitis admitted over a 4-yr period. SETTING: Neurologic intensive care unit in a tertiary referral center. PATIENTS: We identified N-methyl-D-aspartate receptor antibodies in six patients (two male and four female). All seropositive patients presented with a psychiatric prodrome, before developing seizures and obtundation requiring intensive care unit admission. They exhibited limb and truncal stereotypies and orofacial dyskinesias upon weaning sedation. Two patients had ovarian tumors. INTERVENTIONS: Patients were treated with sedation, antiepileptic drugs, and immunotherapy. One patient received a magnesium infusion and ketamine. MEASUREMENTS AND MAIN RESULTS: N-methyl-D-aspartate receptor antibodies were identified in serum samples by an immunofluorescent cell-based assay. Three patients made a good but slow recovery; two were left with severe neurologic deficits; and one died after return to the referring hospital. These patients accounted for approximately 20% of all patients admitted with encephalitis to this referral center. CONCLUSIONS: N-methyl-D-aspartate receptor antibodies should be tested in patients with hyperkinetic encephalitis and neuropsychiatric prodrome admitted to the intensive care unit. The disorder is probably not rare and is potentially treatable.

TI-relaxation time changes over five years in relapsing-remitting multiple sclerosis.

The pathological effects of multiple sclerosis are not confined to lesions; tissues that appear normal on conventional magnetic resonance imaging scans are also affected, albeit subtly. One imaging technique that has proven sensitive to such effects is T1-relaxation time measurement, with previous work demonstrating abnormalities in normal-appearing white matter and grey matter. In this work we investigated the evolution of T1-relaxation time changes in normal-appearing white matter and grey matter in relapsing-remitting multiple sclerosis. Three- and five-year follow-up data from 35 people with clinically early (a mean of 1.6 years from first clinical event) relapsing-remitting multiple sclerosis and 15 healthy controls were analysed. T1-relaxation time histograms were extracted from normal-appearing white matter and grey matter, and mean, peak height and peak location values were estimated. T1-relaxation time peak height declined in the multiple sclerosis normal-appearing white matter and grey matter, but not the control group (rate difference p = 0.024 in normal-appearing white matter, in normal-appearing grey matter p = 0.038); other T1-relaxation time changes were not significantly different between groups. Changes in T1-relaxation time measures did not correlate with increases in brain T2-weighted lesion loads or Expanded Disability Status Scale scores. These results suggest that the processes underlying changes in normal-appearing white matter and grey matter T1-relaxation times are not immediately linked to white matter lesion formation, and may represent more diffuse but progressive sub-clinical pathology in relapsing-remitting multiple sclerosis.

Longitudinal evaluation of clinically early relapsing-remitting multiple sclerosis with diffusion tensor imaging.

Diffusion tensor imaging (DTI) parameters such as mean diffusivity (MD) and fractional anisotropy (FA) assess aspects of structural integrity within tissue. In relapsing-remitting (RR) multiple sclerosis (MS), abnormalities in normal appearing brain tissue (NABT) have been shown cross-sectionally. The evolution of these abnormalities over time is unclear. We present a longitudinal study investigating early RR MS subjects. The aims were to determine DTI changes over two years and assess the potential of DTI as a longitudinal quantitative marker at this stage of MS. Fifteen controls and 28 patients with RR MS (median disease duration 1.9 years; median EDSS 1.5) had DTI yearly for two years. NABT and whole brain tissue (NABT plus lesions) FA and MD histograms analysed. At baseline, differences in FA were noted between patients and controls (mean [p = 0.042] and peak height [p = 0.008]), while at two years differences in MD were observed (mean [p = 0.008] and peak location [p = 0.024]). However there were no significant DTI differences in longitudinal rates of change between patients and cohorts. In conclusion, although subtle NABT abnormalities were detected in early RR MS, the absence of longitudinal change suggests a limited role for global DTI assessment of NABT in following the early disease course.

Cerebral atrophy measurement in clinically isolated syndromes and relapsing remitting multiple sclerosis: a comparison of registration-based methods.

BACKGROUND AND PURPOSE: Brain atrophy is a proposed marker of disease progression in multiple sclerosis (MS). Many magnetic resonance imaging-based methods of atrophy quantification exist, but their relative sensitivity and precision is unclear. Our aim was to compare atrophy rates from the brain boundary shift integral (BBSI), structural image evaluation, using normalization of atrophy (SIENA) (both registration-based methods) and segmented brain volume difference, in patients with clinically isolated syndromes (CIS), relapsing remitting MS (RRMS), and controls. METHODS: Thirty-seven CIS patients, 30 with early RRMS and 16 controls had T1-weighted volumetric imaging at baseline and 1 year. Brain atrophy rates were determined using segmented brain volume difference, BBSI, and SIENA. RESULTS: BBSI and SIENA were more precise than subtraction of segmented brain volumes and were more sensitive distinguishing RRMS subjects from controls. A strong correlation was observed between BBSI and SIENA. Atrophy rates were greater in CIS and RRMS subjects than controls (RRMS P < .001). With all methods, significantly greater atrophy rates were observed in CIS patients who developed clinically definite MS relative to subjects who did not. CONCLUSION: Registration-based techniques are more precise and sensitive than segmentation-based methods in measuring brain atrophy, with BBSI and SIENA providing comparable results.

Localization of grey matter atrophy in early RRMS : A longitudinal study.

Previous MR studies have established that grey matter (GM) atrophy occurs in multiple sclerosis (MS) from clinical onset. However, it is uncertain whether early GM atrophy is global or has certain local predilections: using Voxel-Based Morphometry this study aimed to address this question.Twenty-one patients with early RRMS (mean age 36 years, mean disease duration from symptom onset 25.8 months) and 10 healthy control subjects (mean age 37 years) were studied. T(1)-weighted three-dimensional MRI images were acquired at baseline and two year follow-up, and analysed with statistical parametric mapping software (SPM2). Two-sample t-tests (p < 0.05 corrected for multiple comparisons at cluster level) were used to compare GM maps from all patients and controls on a voxel-by-voxel basis. At baseline, no GM region appears significantly atrophic in MS subjects compared with controls. However, during the follow-up period significantly greater atrophy occurred in both thalami and the right lateral prefrontal cortex of MS patients when compared with controls. By year two, cross-sectional group comparison revealed GM atrophy in the thalami of MS patients relative to controls. The rate of thalamic atrophy in MS subjects was correlated with changes in EDSS during the follow-up period. This study suggests that early in the clinical course of RRMS, the thalamic atrophy is more consistently apparent than regional cortical atrophy.

Principal component and linear discriminant analysis of T1 histograms of white and grey matter in multiple sclerosis.

Twenty-three relapsing remitting multiple sclerosis (RRMS) patients and 14 controls were imaged to produce normal-appearing white and grey matter T1 histograms. These were used to assess whether histogram measures from principal component analysis (PCA) and linear discriminant analysis (LDA) out-perform traditional histogram metrics in classification of T1 histograms into control and RRMS subject groups and in correlation with the expanded disability status score (EDSS). The histograms were classified into one of two groups using a leave-one-out analysis. In addition, the patients were scanned serially, and the calculated parameters correlated with the EDSS. The classification results showed that the more complex techniques were at least as good at classifying the subjects as histogram mean, peak height and peak location, with PCA/LDA having success rates of 76% for white matter and 68%/65% for grey matter. No significant correlations were found with EDSS for any histogram parameter. These results indicate that there is much information contained within the grey matter as well as the white matter histograms. Although in these histograms PCA and LDA did not add greatly to the discriminatory power of traditional histogram parameters, they provide marginally better performance, while relying only on data-driven feature selection.

Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis.

OBJECTIVES: The concentration in plasma of the brain-specific cholesterol metabolite cerebrosterol has been proposed as a biomarker of neurodegeneration in multiple sclerosis (MS) and other neurological diseases. It is unknown, however, which pathophysiological process in MS best accounts for variations in plasma cerebrosterol. PATIENTS AND METHODS: In this study, we related plasma cerebrosterol concentrations in 46 MS patients - 27 with a relapsing-remitting (RR) disease course and 19 with a primary progressive (PP) course - to three conventional magnetic resonance imaging measures: on T(1)-weighted brain scans, volume of gadolinium-enhanced lesions (a marker of active inflammation) and hypointense lesions (a marker of edema or axonal loss) and on T(2)-weighted scans, volume of hyperintense lesions (a marker of disease extent). RESULTS: By multiple-regression analysis, we uncovered negative correlations between the cerebrosterol-cholesterol ratio in plasma and both age at sampling (beta=-0.35 and p=0.079 in RRMS; beta=-0.76 and p=0.006 in PPMS) and volume of T(2)-weighted lesions (beta=-0.52 and p=0.078 in RRMS; beta=-0.50 and p=0.247 in PPMS). CONCLUSION: We hypothesize that decreases in plasma cerebrosterol may reflect the total spatiotemporal burden of MS-the cumulative effects of its dissemination in space and its duration in time.

Upper cervical cord area in early relapsing-remitting multiple sclerosis: cross-sectional study of factors influencing cord size.

PURPOSE: To determine whether the upper cervical cord area (UCCA) is influenced by disease effect in early relapsing-remitting multiple sclerosis (MS), using statistical modeling to account for potential covariates. MATERIALS AND METHODS: A cohort of 39 patients were studied cross-sectionally within three years of first symptom onset (median disease duration = 1.6 years) and compared with 26 healthy controls. The UCCA was measured from axial reconstructions of three-dimensional T1-weighted scans with automated detection of the edge of the cord. Statistical analysis adjusted for factors such as total intracranial volume (TICV) and gender. Clinical correlations, in particular those thought likely to be related to cord pathology, were also investigated. RESULTS: No significant disease effect was noted on UCCA (P = 0.685), although there was borderline evidence of a lower UCCA in patients with symptoms of bowel or bladder disturbance (P = 0.043). A strong association was noted between UCCA and TICV (r = 0.558; P < or = 0.001), and there was a trend for females to have a smaller UCCA (P = 0.062). The latter finding appeared to reflect a gender-related difference in TICV (P < or = 0.001). CONCLUSION: Atrophy of the upper cervical cord is not readily apparent in most patients early in the course of relapsing-remitting MS. In evaluations of disease-related changes in the UCCA in cross-sectional studies, TICV and gender should be considered as potentially confounding covariates.

The clinical significance of an intrathecal monoclonal immunoglobulin band: a follow-up study.

BACKGROUND: Intrathecal oligoclonal band synthesis occurs in 95% of patients with clinically definite MS but may also occur in the context of CNS infection and other inflammatory conditions. By contrast, the significance of an intrathecal synthesis of a monoclonal band remains uncertain. Previously, an association between a single intrathecal band and CNS lymphoma has been reported but a relationship has also been shown with diagnoses more usually associated with an oligoclonal pattern. At present, it is not known whether a single band will convert to an oligoclonal response with time. METHODS: Data were obtained from patients who had CSF and serum analyzed by isoelectric focusing (IEF) at the authors' institutions over a 6-year period. Clinical details were acquired for those who underwent repeat lumbar puncture after an initial CSF examination revealed an intrathecal monoclonal immunoglobulin G band. RESULTS: Of the 31 patients identified as having an initial intrathecal monoclonal band, clinical details were available for 27. Of those, 9 were found on subsequent lumbar puncture to have developed an intrathecal oligoclonal response. CONCLUSIONS: Among those subjects who developed oligoclonal bands, there was a propensity for either a diagnosis of MS or clinically isolated syndromes due to demyelination. In the 18 subjects who either reverted to having normal CSF IEF or continued to exhibit only the monoclonal band, no cases of MS were encountered. Importantly, one of these had cerebral lymphoma.

Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes.

While brain atrophy occurs early in the clinical course of multiple sclerosis, exactly how early, which tissues are affected and the rate at which early atrophy occurs are unclear. Regional brain atrophy was investigated in 58 patients recruited within 3 months of onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis, who were followed-up for 3 years. At 3 years, 31 subjects had developed multiple sclerosis as defined by the McDonald criteria, while 27 had not (13 had MRI-visible brain lesions and 14 did not). In those who developed multiple sclerosis, the mean decrease in grey matter fractional volume (GMF, as a fraction of total intracranial volume) was -0.017 (-3.3%) and was significantly larger than in the combined lesion-positive and lesion-negative CIS subjects [-0.005 (-1.1%), P = 0.001]. No decrease in white matter fractional volumes (WMF) was seen. Change in GMF correlated only modestly with the change in T2 lesion volume from baseline to year 3 (r = -0.428, P = 0.004). These results suggest that progressive grey matter, but not white matter, atrophy is seen in the earliest clinically observable stages of relapse onset multiple sclerosis, and this is only moderately related to lesion accumulation. Longer-term follow-up is required to determine whether early grey matter atrophy is associated with subsequent disability or cognitive impairment.