The feasibility of assessing cognitive and motor function in multiple sclerosis patients using robotics.

BACKGROUND: Multiple sclerosis (MS) causes pervasive motor, sensory and cognitive dysfunction. The Expanded Disability Status Scale (EDSS) is the gold standard for assessing MS disability. The EDSS is biased towards mobility and may not accurately measure MS-related disabilities in the upper limb or in cognitive functions (e.g. executive function). OBJECTIVE: Our objectives were to determine the feasibility of using the Kinarm robotic system to quantify neurological deficits related to arm function and cognition in MS patients, and examine relationships between traditional clinical assessments and Kinarm variables. METHODS: Individuals with MS performed 8 robotic tasks assessing motor, cognitive, and sensory ability. We additionally collected traditional clinical assessments and compared these to the results of the robotic assessment. RESULTS: Forty-three people with MS were assessed. Most participants could complete the robotic assessment. Twenty-six (60%) were impaired on at least one cognitive task and twenty-six (60%) were impaired on at least one upper-limb motor task. Cognitive domain task performance correlated most strongly with the EDSS. CONCLUSIONS: Kinarm robotic assessment of people with MS is feasible, can identify a broad range of upper-limb motor and sensory, as well as cognitive, impairments, and complements current clinical rating scales in the assessment of MS-related disability.

Perceptions and barriers to competency-based education in Canadian postgraduate medical education.

RATIONALE: Competency-based education (CBE) is currently being implemented across Canadian postgraduate medical education programmes through Competence by Design (CBD).1 Queen's University received permission to initiate CBE in all programmes simultaneously starting in 2017; an institutional initiative termed Competency-based medical education (CBME).2 We describe our initial experiences to highlight perceptions and barriers and facilitate implementation at other centers. METHODS: Anonymous online surveys were administered to faculty and residents transitioning to CBE (138 respondents) including (a) Queen's programme leaders (Programme Directors and CBME Leads) [n = 27], (b) Queen's residents [n = 102], and (c) Canadian neurology programme directors [n = 9] and were analysed using descriptive and inferential statistical techniques. RESULTS: Perceptions were favourable (x = 3.55/5, SD = 0.71) and 81.6% perceived CBE enhanced training; however, perceptions were more favourable among faculty. Queen's programme leaders indicated that CBE did not improve their ability to provide negative feedback. Queen's residents did not perceive improved quality of feedback. National Canadian neurology programme directors did not perceive that their institutions had adequately prepared them. There was variability in barriers perceived across groups. Queen's programme leaders were concerned about resident initiative. Queen's residents felt that assessment selection and faculty responsiveness to feedback were barriers. Canadian neurology programme directors were concerned about access to information technology. RECOMMENDATIONS: Our results indicate that faculty were concerned about the reluctance of residents to actively participate in CBE, while residents were hesitant to assume such a role because of lack of familiarity and perceived benefit. This discrepancy indicates attention should be devoted to (a) institutional administrative/educational supports, (b) faculty development around feedback/assessment, and (c) resident development to foster ownership of their learning and familiarity with CBE.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

INTRODUCTION: Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. OBJECTIVES: To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. METHODS: Patients with simultaneous copper deficiency (<0.78 µg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. RESULTS: 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 µg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. CONCLUSIONS: An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance.

Epidermal nerve fibers: confidence intervals and continuous measures with nerve conduction.

OBJECTIVES: Our first objective was to explore the value of estimating 95% confidence intervals (CIs) of epidermal nerve fibers (ENFs)/mm for number of sections to be evaluated and for confidently judging normality or abnormality. Our second objective was to introduce a new continuous measure combining nerve conduction and ENFs/mm. METHODS: The 95% CI studies were performed on 1, 1-2, 1-3 - - - 1-10 serial skip sections of 3-mm punch biopsies of leg and thigh of 67 healthy subjects and 23 patients with diabetes mellitus. RESULTS: Variability of differences of ENFs/mm counts (and 95% CIs) from evaluation of 1, 1-2, 1-3 - - - 1-9 compared with 1-10 serial skip sections decreased progressively without a break point with increasing numbers of sections evaluated. Estimating 95% CIs as sections are evaluated can be used to judge how many sections are needed for adequate evaluation, i.e., only a few when counts and 95% CIs are well within the range of normality or abnormality and more when values are borderline. Also provided is a methodology to combine results of nerve conduction and ENFs/mm as continuous measures of normality or abnormality. CONCLUSION: Estimating 95% CIs of ENFs/mm is useful to judge how many sections should be evaluated to confidently declare counts to be normal or abnormal. Also introduced is a continuous measure of both large-fiber (nerve conduction) and small-fiber (ENFs/mm) normal structures/functions spanning the range of normality and abnormality for use in therapeutic trials.

A case of sensory ataxia as the presenting manifestation of neurosarcoidosis.

Sarcoidosis rarely selectively affects the cauda equina with characteristic motor and sensory impairments.Using imaging, we report a case of cauda equina polyradiculopathy presenting with progressive sensory ataxia without clinical or electrophysiological evidence of motor involvement. Neurosarcoidosis was diagnosed pathologically by proximal dorsal root biopsy after systemic investigations for inflammatory, infectious, and neoplastic etiologies were found to be negative. There was clinical and radiographic improvement with corticosteroids. In addition, we review previously reported cases of cauda equina sarcoidosis.

Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2.

Charcot-Marie-Tooth (CMT) disease is among the most common inherited neurological disorders. Mutations in the gene mitofusin 2 (MFN2) cause the axonal subtype CMT2A, which has also been shown to be associated with optic atrophy, clinical signs of first motor neuron involvement, and early onset stroke. Mutations in MFN2 account for up to 20-30% of all axonal CMT type 2 cases. To further investigate the prevalence of MFN2 mutations and to add to the genotypic spectrum, we sequenced all exons of MFN2 in a cohort of 39 CMT2 patients. We identified seven variants, four of which are novel. One previously described change was co-inherited with a PMP22 duplication, which itself causes the demyelinating form CMT1A. Another mutation was a novel in frame deletion, which is a rare occurrence in the genotypic spectrum of MFN2 characterized mainly by missense mutations. Our results confirm a MFN2 mutation rate of ~15-20% in CMT2.

Herpes simplex encephalitis presenting with exclusively frontal lobe involvement.

The authors report a patient with herpes simplex encephalitis who presented with magnetic resonance imaging (MRI) lesions exclusively in the frontal lobes, including the bilateral anterior cingulate gyri. She is making a good recovery after therapy with intravenous acyclovir. A similar presentation with a fatal outcome was previously reported by Rose et al (Neurology 42: 1809-1812, 1992). MRI shows temporal lesions in most patients with herpes simplex encephalitis, whereas occasional patients have normal imaging. A high index of suspicion for the diagnosis of herpes simplex encephalitis should be maintained when a patient presents with fever and brain lesions involving extratemporal limbic system structures.

FOS and FOSB expression in the medial preoptic nucleus pars compacta of maternally active C57BL/6J and DBA/2J mice.

C57BL/6J and DBA/2J inbred mice differ in aspects of maternal behavior and in the morphology of the medial preoptic nucleus (MPO), suggesting a possible association. DBA/2J mice have a compact subnucleus in the MPO, the MPOpc, that is sexually dimorphic and absent in C57BL/6J mice. To determine whether MPOpc cells are activated by maternal behavior, FOS and FOSB immunohistochemistry was performed on brain sections of C57BL/6J and DBA/2J mothers following the return of their pups after a separation of 2 days. In both light and dark phases of the daily cycle, stimulation of DBA/2J mothers evoked an increase in FOS- and FOSB-immunoreactivity in the MPOpc. Stimulated C57BL/6J mice, which lack the MPOpc, did not show an increase in cellular activity in the corresponding MPO region. Cells immediately lateral to the MPOpc were activated by pup stimulation, in both strains. These results suggest that MPOpc cells are active during maternal behavior, and that strain differences in maternal behavior are related to anatomical differences in the MPO.