A Case of Pediatric Guillain-Barré Syndrome After Respiratory Syncytial Virus Infection.

We report a two-year-old girl whose progressive lower extremity weakness was masked by a respiratory presentation, only to be identified as having Guillain-Barré syndrome in the context of respiratory syncytial virus bronchiolitis. This case adds to the expanding literature of postinfectious demyelinating disorders in very young children, which seem to be unrelated to particular antigenic triggers.

Case report: An EEG captured case of migralepsy/migraine aura-triggered seizures.

Introduction: Migraine and epilepsy are common chronic neurological disorders presenting with paroxysmal attacks of transient cerebral dysfunction, followed by subsequent return to baseline between episodes. The term "migralepsy" has been proposed to define migraine-triggered epileptic seizures classified by the ICHD-III as a complication of migraine with an aura. Case: A 55-year-old man with a 30-year history of migraine without aura presented with a new onset left parietal pain accompanied by visual disturbances occurring up to 20 times per day. His visual distortions included kaleidoscopic vision, flashes of shadows, and a right superior quadrantanopia lasting 20 min. He described discrete 2-min episodes of scintillating scotomas in his right visual field. Ictal EEG demonstrated a left occipital onset focal aware seizure with his clinical symptoms. The patient was started on valproic Acid and has remained asymptomatic. Discussion: The diagnostic criteria as set out by the ICHD-III for migralepsy and other syndromes with migrainous and ictal features remain confusing for practitioners as there is much overlap in clinical manifestations of these entities. EEG should be obtained when ictal features are noted among patients presenting with headache.

Medical Students' Knowledge and Perception of Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) is a well-established neurosurgical procedure commonly used in movement and psychiatric disorders. Its widespread clinical implementation, however, may not be commensurate with medical education. No current assessment of medical student's understanding of DBS as a treatment option for indicated conditions is available, potentially threatening the availability of DBS to future patients. The aim of the present study is to explore the current knowledge and attitudes of medical students toward DBS as a treatment modality. METHODS: A total of 65 medical students at Virginia Tech Carilion School of Medicine were surveyed regarding their knowledge of DBS. The survey consisted of a 25-item questionnaire including a demographic section and 3 separate inventories designed to assess bias, knowledge, and self-assessment of knowledge specific to DBS therapy. Students in pre-clinical and clinical years were analyzed separately to describe changes in knowledge or attitude associated with clinical exposure to DBS. Comparisons were analyzed using t tests, ANOVA, and Pearson correlations. RESULTS: Of surveyed students, 36% were unsure of the FDA approval status of DBS treatment; 65% of students believed they had not been adequately educated about DBS and its utility; and 10.6% of students believed that DBS is likely associated with severe adverse effects and/or brain damage. The overall baseline attitudes of students toward DBS were positive. There was no observed difference between surveyed pre-clinical and clinical students, highlighting a lack of exposure throughout the clinical years of medical school education. CONCLUSION: Although DBS is an effective treatment modality for various conditions, current education is non-commensurate with its application, which can negatively impact awareness and understanding for its implications by medical professionals. In order to better serve patients who may benefit from DBS, medical curricula must change to educate future physicians on the benefit of this intervention.

Systematic content analysis of patient evaluations of START NOW psychotherapy reveals practical strategies for improving the treatment of opioid use disorder.

BACKGROUND: Clinical trials provide consistent evidence for buprenorphine's efficacy in treating opioid use disorder (OUD). While the Drug Addiction Treatment Act of 2000 requires physicians to combine medication-assisted treatment (MAT) with behavioral intervention, there is no clear evidence for what form or elements of psychotherapy are most effective when coupled with MAT to treat OUD. This investigation involves focus groups designed to collect patient opinions about a specific psychotherapy, called START NOW, as well as general beliefs about various elements of psychotherapy for treating OUD. Our analysis reveals trends about patient preferences and strategies for improving OUD treatment. METHODS: Subjects included patients enrolled in buprenorphine/naloxone MAT at our institution's office-based opioid treatment program. All subjects participated in a single START NOW group session, which was led by a provider (physician or nurse practitioner trained and standardized in delivering START NOW). Consented subjects participated in satisfaction surveys and audio-recorded focus groups assessing individual beliefs about various elements of psychotherapy for treating OUD. RESULTS: Overall, 38 different focus groups, 92 participation events, and 44 unique subjects participated in 1-to-6 different START NOW session/audio-recorded focus group sessions led by a certified moderator. Demographic data from 36/44 subjects was collected. Seventy-five percent (33/44) completed the START NOW Assessment Protocol, which revealed self-reported behavioral trends. Analysis of all 92 START NOW Satisfaction Questionnaire results suggests that subjects' opinions about START NOW improved with increased participation. Our analysis of audio-recorded focus groups is divided into three subsections: content strategies for new psychotherapies, implementation strategies, and other observations. For example, participants request psychotherapies to target impulsivity and to teach future planning and build positive relationships. CONCLUSIONS: The results of this study may guide implementation of psychotherapy and improve the treatment of OUD, especially as it relates to improving the modified START NOW program for treating OUD. Our study also reveals a favorable outlook of START NOW with increased participation, suggesting that any initial reticence to this program can be overcome to allow for effective implementation.

Familial Alzheimer's Disease Mutations within the Amyloid Precursor Protein Alter the Aggregation and Conformation of the Amyloid-ß Peptide.

Most cases of Alzheimer's disease (AD) are sporadic, but a small percentage of AD cases, called familial AD (FAD), are associated with mutations in presenilin 1, presenilin 2, or the amyloid precursor protein. Amyloid precursor protein mutations falling within the amyloid-ß (Aß) sequence lead to a wide range of disease phenotypes. There is increasing evidence that distinct amyloid structures distinguished by amyloid conformation-dependent monoclonal antibodies have similarly distinct roles in pathology. It is possible that this phenotypic diversity of FAD associated with mutations within the Aß sequence is due to differences in the conformations adopted by mutant Aß peptides, but the effects of FAD mutations on aggregation kinetics and conformational and morphological changes of the Aß peptide are poorly defined. To gain more insight into this possibility, we therefore investigated the effects of 11 FAD mutations on the aggregation kinetics of Aß, as well as its ability to form distinct conformations recognized by a panel of amyloid conformation-specific monoclonal antibodies. We found that most FAD mutations increased the rate of aggregation of Aß. The FAD mutations also led to the adoption of alternative amyloid conformations distinguished by monoclonal antibodies and resulted in the formation of distinct aggregate morphologies as determined by transmission electron microscopy. In addition, several of the mutant peptides displayed a large reduction in thioflavin T fluorescence, despite forming abundant fibrils indicating that thioflavin T is a probe of conformational polymorphisms rather than a reliable indicator of fibrillization. Taken together, these results indicate that FAD mutations falling within the Aß sequence lead to dramatic changes in aggregation kinetics and influence the ability of Aß to form immunologically and morphologically distinct amyloid structures.

The Anti-Amyloid-ß Monoclonal Antibody 4G8 Recognizes a Generic Sequence-Independent Epitope Associated with α-Synuclein and Islet Amyloid Polypeptide Amyloid Fibrils.

Recently we reported that several monoclonal antibodies that recognize linear segments of amyloid-ß (Aß) also recognize amyloid fibrils, but not monomers of unrelated sequences, indicating that recognition of a linear sequence segment is not a reliable indicator of sequence specificity. We asked whether any of the commonly used commercially available Aß antibodies also recognize fibrils of unrelated sequence. Here we report that 4G8, which recognizes residues 18-23 of the Aß sequence and is widely believed to be sequence-specific, also recognizes fibrils formed from α-synuclein and islet amyloid polypeptide (IAPP). The recognition of amyloid fibrils is aggregation-dependent because 4G8 does not recognize α-synuclein or IAPP monomer. 4G8 also stains fibrillar α-synuclein aggregates in human multiple system atrophy brain where it colocalizes with anti-α-synuclein monoclonal antibody LB509 immunoreactivity. We also found that LB509 recognizes Aß fibrils, but not monomer, indicating that generic epitope-reactive antibodies are also produced in response to α-synuclein immunization. Taken together, our results indicate that generic fibril conformational epitope specificity may be a pervasive property among monoclonal antibodies raised against amyloid-forming antigens and that the specificity of their immunoreactivity should be rigorously established and otherwise interpreted with caution.

Monoclonal antibodies against Aß42 fibrils distinguish multiple aggregation state polymorphisms in vitro and in Alzheimer disease brain.

Amyloidogenic proteins generally form intermolecularly hydrogen-bonded ß-sheet aggregates, including parallel, in-register ß-sheets (recognized by antiserum OC) or antiparallel ß-sheets, ß-solenoids, ß-barrels, and ß-cylindrins (recognized by antiserum A11). Although these groups share many common properties, some amyloid sequences have been reported to form polymorphic structural variants or strains. We investigated the humoral immune response to Aß42 fibrils and produced 23 OC-type monoclonal antibodies recognizing distinct epitopes differentially associated with polymorphic structural variants. These mOC antibodies define at least 18 different immunological profiles represented in aggregates of amyloid-ß (Aß). All of the antibodies strongly prefer amyloid aggregates over monomer, indicating that they recognize conformational epitopes. Most of the antibodies react with N-terminal linear segments of Aß, although many recognize a discontinuous epitope consisting of an N-terminal domain and a central domain. Several of the antibodies that recognize linear Aß segments also react with fibrils formed from unrelated amyloid sequences, indicating that reactivity with linear segments of Aß does not mean the antibody is sequence-specific. The antibodies display strikingly different patterns of immunoreactivity in Alzheimer disease and transgenic mouse brain and identify spatially and temporally unique amyloid deposits. Our results indicate that the immune response to Aß42 fibrils is diverse and reflects the structural polymorphisms in fibrillar amyloid structures. These polymorphisms may contribute to differences in toxicity and consequent effects on pathological processes. Thus, a single therapeutic monoclonal antibody may not be able to target all of the pathological aggregates necessary to make an impact on the overall disease process.