A Diverse Specialty: What Students Teach Us About Neurology and "Neurophobia".

OBJECTIVE: To explore what elective students learn about the specialty of Neurology. METHODS: A prospective qualitative study using pre- and post-elective written questionnaires. RESULTS: Analysis concentrated on three main themes: What did students learn about the specialty of Neurology? What would they change about their experience? Did their opinions change? Major findings were (i) pre- and post-elective the most frequent response for "what is the best thing about Neurology?" was the "process of localization" and (ii) post-elective students were less likely to cite the challenge or problem-solving aspect of Neurology as the best thing while more emphasized the importance of the physical exam and the variety of cases. (iii) Students were most surprised by the scope of neurological practice. (iv) They would diversify the setting of their elective to include less time spent in the emergency room and more time in clinic. (v) The perception of Neurology as a specialty in which patients have a poor prognosis was the opinion that changed the most. CONCLUSIONS: Showcasing the diversity of cases and careers in Neurology may be a useful strategy to increase interest in the specialty and reduce neurophobia. Lectures or small groups early in medical school should concentrate on clear examples of common neurological conditions and emphasize the role of general neurologists and subspecialists involved in patient care. Whenever possible students should rotate through different clinics and not concentrate exclusively on emergency room and in-patient cases.

Lenalidomide treatment and prognostic markers in relapsed or refractory chronic lymphocytic leukemia: data from the prospective, multicenter phase-II CLL-009 trial.

Efficacy of lenalidomide was investigated in 103 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated on the prospective, multicenter randomized phase-II CLL-009 trial. Interphase cytogenetic and mutational analyses identified TP53 mutations, unmutated IGHV, or del(17p) in 36/96 (37.5%), 68/88 (77.3%) or 22/92 (23.9%) patients. The overall response rate (ORR) was 40.4% (42/104). ORRs were similar irrespective of TP53 mutation (36.1% (13/36) vs 43.3% (26/60) for patients with vs without mutation) or IGHV mutation status (45.0% (9/20) vs 39.1% (27/68)); however, patients with del(17p) had lower ORRs than those without del(17p) (21.7% (5/22) vs 47.1% (33/70); P=0.049). No significant differences in progression-free survival and overall survival (OS) were observed when comparing subgroups defined by the presence or absence of high-risk genetic characteristics. In multivariate analyses, only multiple prior therapies (⩾3 lines) significantly impacted outcomes (median OS: 21.2 months vs not reached; P=0.019). This analysis indicates that lenalidomide is active in patients with relapsed/refractory CLL with unfavorable genetic profiles, including TP53 inactivation or unmutated IGHV. (ClinicalTrials.gov identifier: NCT00963105).

The usefulness of gadolinium-enhanced images on a follow-up magnetic resonance image in suspected multiple sclerosis.

PURPOSE: Multiple sclerosis diagnostic criteria include the presence of gadolinium-enhancing lesions when determining dissemination in space and time. Gadolinium is expensive, increases scan time and patient discomfort, and can, rarely, cause serious adverse effects. Our objective was to determine the usefulness of including gadolinium-enhanced images as part of a follow-up brain magnetic resonance imaging (MRI) in patients with a clinically isolated syndrome. METHODS: Consecutive patients seen between 2008 and 2010 with a clinically isolated syndrome suggestive of multiple sclerosis were prospectively enrolled, had a non-gadolinium-enhanced brain MRI, and consented to a follow-up gadolinium-enhanced brain MRI. The primary outcome was a comparison of the number of patients diagnosed with multiple sclerosis compared with the number who would have been diagnosed without the gadolinium-enhanced images. RESULTS: Twenty-one patients enrolled, and 2 withdrew. Follow-up MRIs were performed a median of 241 days after the initial MRI. Eleven patients met the primary outcome and were diagnosed with multiple sclerosis: 6 as a result of a second clinical attack and 5 by using imaging criteria for dissemination in space and time. If the gadolinium-enhanced images had not been obtained, then there would have been no change in the primary outcome. CONCLUSIONS: In Canadian centers with similar MRI waiting times to those in our study, the routine use of gadolinium as part of a follow-up MRI in patients with suspected multiple sclerosis may not be clinically useful. Gadolinium-enhanced images could still be obtained on an as-needed basis for specific clinical indications.

Improving the neurological exam skills of medical students.

OBJECTIVE: Determine if distributed practice of of neurological exam (NE) skills in first year medical school produces sustained improvements in the skills of second year students. METHODS: A prospective, controlled, non-blinded study conducted at McGill University (class size = 180 students). Expanded teaching of muscle stretch reflexes was provided to first year medical students. A structured examination of muscle stretch reflexes (max score = 100) was administered in second year medical school after a required two week rotation in Neurology. Results for class A (received the intervention in first year) were compared to the results for the preceding class B (had not received the intervention). RESULTS: 77 of 177 (44%) eligible in class A and 69 of 166 (42%) eligible students in class B participated. Results were analyzed separately for each of the two examiners. Mean (SD) scores were 95.2 (5.6) for class A (intervention) and 81.7 (11.1) for class B (control) for the first examiner and 90.4 (8.2) for class A and 83.8 (11.7) for class B for the second examiner. Results were statistically significant (Mann-Whitney test z = 5.27, p<0.0001 first examiner and z = 2.67, p<0.0038 second examiner). CONCLUSIONS: Distributed practice of muscle stretch reflexes during first year medical school results in improved performance by second year medical students after their mandatory clinical rotation in neurology, even when examined up to 14 months after the intervention. This finding has implications for the teaching of the NE.

EEG in suspected syncope: do EEGs ordered by neurologists give a higher yield?

BACKGROUND: Prior studies have shown that the electroencephalogram (EEG) is of low diagnostic yield in the evaluation of syncope but have not looked at the yield according to referring physician specialty. The goals of this study were to determine if the yield of the EEG is higher when ordered by neurologists and whether EEGs with abnormal findings resulted in any significant change in patient management. METHODS: We retrospectively reviewed the records of the EEGs requested for a clinical diagnosis of syncope, convulsive syncope, loss of consciousness, or falls from 2003 to 2007 at our institution. We obtained further information from the medical record of patients with an abnormal EEG. RESULTS: Of 517 EEGs meeting our inclusion criteria, only 57 (11.0%) were read as abnormal. No EEG was positive for epileptiform activity and only 9 (1.6%) showed potentially epileptic activity. EEGs ordered by neurologists did not have a higher yield compared to non-neurologists. Five abnormal EEGs resulted in further investigations being ordered. One patient was ultimately started on phenytoin. CONCLUSIONS: EEGs requested for the evaluation of patients with suspected syncope have an extremely low diagnostic yield and do not significantly alter the management of the patients, regardless of the specialty of the referring physician.

Radial neuropathies in wheelchair users.

This report presents two cases with a radial neuropathy caused by compression between the spiral groove of the humerus and a hard wheelchair surface. One case involved the arm rest and the second a hard, vertical support of the back of the wheelchair. Close attention to the placement of the upper arms in relation to the surfaces of the wheelchair is required to avoid this complication in wheelchair users.

The essential neurologic examination: what should medical students be taught?

BACKGROUND: Graduating medical students often identify the neurologic examination (NE) as one of the clinical skills with which they are least comfortable. We hypothesized that this is because they are unsure about which elements of the NE are important, and conducted a study 1) to identify whether neurologists agree about the essential elements of the NE and 2) to determine whether the views of medical students about what is essential differ from those of neurologists. METHODS: Using a Delphi process, we asked McGill University neurologists which elements of the NE they would perform at least 80% of the time in a common clinical scenario. We confirmed the results in a sample of Canadian neurologists, and then compared the results of the McGill neurologists to a sample of graduating McGill University medical students. RESULTS: The neurologists surveyed rated 22 items of the NE as essential, and there was a high degree of consensus about which items were essential. Medical student ratings of the importance of NE items were largely similar to those of the neurologists, although there were some noteworthy discrepancies. CONCLUSIONS: The anxiety felt by medical students regarding the neurologic examination (NE) seems unlikely to be solely due to uncertainty about which elements of the NE are important. Expert consensus about the essential elements of the NE and awareness of areas where neurologist and student views differ should be used to guide teaching of the NE.

How well does neurology residency mirror practice?

OBJECTIVE: To report the residency training experience of two neurologists, focusing on setting and diagnoses encountered. METHODS: Data from prospective patient logs kept by the authors during residencies completed a decade apart were compared with each other and the literature. RESULTS: The range of diagnoses was broadly similar between residencies, as were the proportions of common or uncommon disorders, and the proportion of cases without a neurological diagnosis. Although most patients were seen in in-patient settings, the rates at which common neurological conditions and functional disorders were seen was comparable to published experiences of community neurologists. CONCLUSIONS: The diagnostic profile of North American neurology residency appears to be relatively stable, regardless of location or date of training. In several respects, the content of current neurology residencies mirrors clinical practice well. Changes to residency training are doubtless needed, but they should be guided by a clear understanding of the experiences of contemporary trainees.

The p36 isoform of BAG-1 is translated by internal ribosome entry following heat shock.

BAG-1 (also known as RAP46/HAP46) was originally identified as a 46 kDa protein that bound to and enhanced the anti-apoptotic properties of Bcl-2. BAG-1 exists as three major isoforms (designated p50, p46 and p36 or BAG-1L, BAG-1M and BAG-1S respectively) and one minor isoform (p29), which are translated from a common transcript. The differing amino terminus determines both the intracellular location and the repertoire of binding partners of the isoforms which play different roles in a variety of cellular processes including signal transduction, heat shock, apoptosis and transcription. Although in vitro data suggest that the four BAG-1 isoforms are translated by leaky scanning, the patterns of isoform expression in vivo, especially in transformed cells, do not support this hypothesis. We have performed in vivo analysis of the BAG-1 5' untranslated region and shown that translation initiation of the most highly expressed isoform (p36/BAG-1S) can occur by both internal ribosome entry and cap-dependent scanning. Following heat shock, when there is a downregulation of cap-dependent translation, the expression of the p36 isoform of BAG-1 is maintained by internal ribosome entry.

Derivation of a structural model for the c-myc IRES.

We have derived a secondary structure model for the c-myc internal ribosome entry segment (IRES) by using information from chemical probing of the c-myc IRES RNA to constrain structure prediction programs. Our data suggest that the IRES is modular in nature, and can be divided into two structural domains linked by a long unstructured region. Both domains are required for full IRES function. Domain 1 is a complex element that contains a GNNRA apical loop and an overlapping double pseudoknot motif that is topologically unique amongst published RNA structures. Domain 2, the smaller of the two, contains an apical AUUU loop. We have located the ribosome landing site and have shown that ribosomes enter in a 16 nt region downstream of the pseudoknots in a situation similar to that observed in several viral IRESs. To test the structure, several key regions of the IRES were mutated and, interestingly, it appears that some of the structural elements that we have identified function to repress c-myc IRES function. This has profound implications for de-regulation of c-myc expression by mutations occurring in the IRES.

Retinoic acid stimulates the synthesis of a novel heat shock protein in the regenerating forelimb of the newt.

Morphogenetic effects of retinoic acid (RA) on the urodele amphibian limb regenerate pattern have been well documented, but little is known regarding the mechanism of this action of RA at the molecular level. Since exogenous RA, at concentrations sufficient to cause proximalization, represents a significant stress to newts and has been shown previously to elicit increased synthesis of heat shock proteins (HSPs) in mouse embryo limb buds, we investigated the effects of this putative morphogen on the synthesis of members of the 70-kilodalton (70-kDa) stress protein family in amputated forelimbs of the newt Notophthalmus viridescens. Injection (i.p.) of RA in dimethyl sulfoxide (DMSO), at a dose sufficient to cause significant proximal-distal reduplication of the pattern in 50% of animals treated, resulted in increased synthesis and accumulation of a 73-kDa protein with a pI of approximately 6.75. The synthesis of this same protein is increased in limb tissues as a result of a brief 35 degrees C heat shock. This protein is electrophoretically distinct from the newt HSP 70 family members, displays a different partial peptide map, and shows no immunological cross-reactivity with an anti-human HSP 70 monoclonal antibody. It may be a member of a separate family of 70- to 73-kDa HSPs. Interestingly, the synthesis of this protein is increased and it is more abundant in control, proximal moderate-early bud stage regenerates at 6 days after i.p. injection of DMSO than in similarly treated distal regenerates. This protein is, in addition, increased in distal regenerates to proximal levels by a prior injection of RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Abuse histories in 102 cases of multiple personality disorder.

The authors interviewed 102 individuals with clinical diagnoses of multiple personality disorder at four centres using the Dissociative Disorders Interview Schedule. The patients reported high rates of childhood trauma: 90.2% had been sexually abused, 82.4% physically abused, and 95.1% subjected to one or both forms of child abuse. Over 50% of subjects reported initial physical and sexual abuse before age five. The average duration of both types of abuse was ten years, and numerous different perpetrators were identified. Subjects were equally likely to be physically abused by their mothers or fathers. Sexual abusers were more often male than female, but a substantial amount of sexual abuse was perpetrated by mothers, female relatives, and other females. Multiple personality disorder appears to be a response to chronic trauma originating during a vulnerable period in childhood.

Lumbar intervertebral disc prolapse in teenage twins. A case report and review of the literature.

We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect.

Structured interview data on 102 cases of multiple personality disorder from four centers.

Patients with multiple personality disorder (N = 102) at four different centers were interviewed with the Dissociative Disorders Interview Schedule. The presenting characteristics of the patients at all four centers were very similar. The clinical profile that emerged included a history of childhood physical and/or sexual abuse in 97 (95.1%) of the cases. The subjects reported an average of 15.2 somatic symptoms, 6.4 Schneiderian symptoms, 10.2 secondary features of the disorder, 5.2 borderline personality disorder criteria, and 5.6 extrasensory experiences; their average score on the Dissociative Experiences Scale was 41.4. The results indicate that multiple personality disorder has a stable, consistent set of features.

Schneiderian symptoms in multiple personality disorder and schizophrenia.

We report structured interview data from a series of 102 cases of multiple personality disorder (MPD) diagnosed in four centers. Schneiderian first-rank symptoms of schizophrenia were equally common in all four centers. The average MPD patient had experienced 6.4 Schneiderian symptoms. When these 102 cases are combined with two previously reported series of MPD cases, an average of 4.9 Schneiderian symptoms in 368 cases of MPD is noted. This compares with an average of 1.3 symptoms acknowledged by 1,739 schizophrenics in 10 published series. Schneiderian symptoms are more characteristic of MPD than of schizophrenia.

Revision of the Charnley low-friction arthroplasty for recurrent or irreducible dislocation.

Twenty-one cases of the Charnley low-friction arthroplasty were revised because of recurrent or irreducible dislocation. Three main reasons for this revision, usually in combination, were identified: loss of the abductor mechanism due to trochanteric detachment; shortening of the limb due to high placement of the socket or low section of the femoral neck; and malorientation of the components. Sixteen patients had no further problems after revision. One patient had a single dislocation, four had more than one dislocation although they managed to cope with them and did not require a further revision.