Clinical correlates of fear of falling in progressive supranuclear palsy and multiple system atrophy.

BACKGROUND AND PURPOSE: Clinical correlates of fear of falling (FoF) are scarcely studied in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). This study was undertaken to evaluate the clinical correlates of FoF in PSP and MSA. METHODS: This cross-sectional study features motor, cognitive, and psychiatric assessment and longitudinal evaluation of falls and FoF at 6-month follow-up. RESULTS: Twenty-one patients with PSP-parkinsonism, 22 patients with MSA (13 parkinsonian type and nine cerebellar type), and 22 healthy controls were evaluated; 76.2% of patients with PSP and 86.4% of patients with MSA had FoF regardless of falls. Berg Balance Scale (p < 0.001), Tinetti Mobility Test (p < 0.01), Beck Anxiety Inventory (p = 0.001), and Beck Depression Inventory-II (p = 0.01) correlated with FoF in patients with PSP and MSA, whereas Timed Up and Go test (p = 0.01) and Starkstein Apathy Scale correlated only in MSA (p = 0.04). CONCLUSIONS: Mobility, balance, and gait performance as well as anxiety and depression in PSP and MSA, and apathy in MSA, were determinants of FoF. These findings underline the importance of a multidisciplinary approach to FoF in neurodegenerative atypical parkinsonism.

Motor assessment of patients with multiple system atrophy: underuse of the Unified Multiple System Atrophy Rating Scale (UMSARS).

PURPOSE: Despite the availability of the Unified Multiple System Atrophy (MSA) Rating Scale (UMSARS) for almost two decades, studies still use scales developed for Parkinson's disease (PD) or ataxia (ATX). Our aim was to evaluate the use of UMSARS (part II, motor) compared to other motor rating scales in patients with MSA. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was conducted concerning studies of patients with MSA, reporting motor assessment with clinical rating scales, and focusing on the frequency of UMSARS use. RESULTS: We included 261 articles, of which 42.9% did not use UMSARS, but rather scales for PD (59.8%), ATX (24.1%), or both (14.3%). Although UMSARS use increased with time, misuse of PD and ATX scales persists, with no evidence of a decremental trend. CONCLUSIONS: Although higher in observational studies, the misuse of PD and ATX-related scales in MSA patients persists in prospective (planned) trials. Reasons for that must be addressed.

"Los libros y la noche", perspectiva neurológica de la ceguera de Jorge Luis Borges.

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

La obra del erudito argentino Jorge Luis Borges (1899-1986) ha cautivado a los médicos. Asiduo lector con magnífica ironía, le fueron dados "los libros y la noche". Borges padeció una ceguera crónica e irreversible que impulsó gran parte de su obra y ha sido objeto de distintos análisis literarios y diagnósticos desde el punto de vista oftalmológico. Sin embargo, las características de su ceguera han escapado al abordaje neurológico, por lo cual revisamos su obra en busca de datos que sugieran una lesión cerebral concomitante. En su autobiografía relata cómo durante un episodio de septicemia padeció alucinaciones y pérdida del habla; además, en algunos poemas y ensayos describe datos que sugieren "cromatopsia fantasma", lesión de origen cortical. Tras dicho accidente, Borges sobrevivió con un cambio radical en su estilo literario. Aunque un diagnóstico preciso es imposible, su obra literaria nos permite reconocer algunos elementos que sugieren involucramiento cerebral concomitante.

"The books and the night", neurological perspective on Jorge Luis Borges' blindness.

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

Perspectives of People At-Risk on Parkinson's Prevention Research.

 The movement toward prevention trials in people at-risk for Parkinson's disease (PD) is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019 S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with PD. These authors participated as speakers, panelists, and moderators in the "Planning for Prevention of Parkinson's: A Trial Design Forum" hosted by Massachusetts General Hospital in 2021 and 2022. Other authors include a young onset person with Parkinson's (PwP) and retired family physician, an expert in patient engagement in Parkinson's, and early career and veteran movement disorders clinician researchers. Several themes emerged from the at-risk participant voice concerning the importance of early intervention, the legitimacy of their input in decision-making, and the desire for transparent communication and feedback throughout the entire research study process. Challenges and opportunities in the current environment include lack of awareness among primary care physicians and general neurologists about PD risk, legal and psychological implications of risk disclosure, limited return of individual research study results, and undefined engagement and integration of individuals at-risk into the broader Parkinson's community. Incorporating the perspectives of individuals at-risk as well as those living with PD at this early stage of prevention trial development is crucial to success.

Intermittent Apomorphine Use for off Period Rescue in Parkinson's Disease: A Pragmatic Review of over Three Decades of Clinical Experience.

Background: Although proven very efficacious as treatment for Parkinson's disease by Schwab as far back as the 1950s, and later confirmed by Cotzias and colleagues in the early 1970s, use of intermittent subcutaneous injections of the dopamine agonist apomorphine remains limited worldwide. Objectives: To review evidence regarding use of intermittent, on-demand apomorphine as a treatment for off-period disability in Parkinson's disease. Methods: A PRISMA-compliant structured literature search was carried out with a focus on clinical effect (motor improvement, daily off time decrease; latency, duration), antiemetic prophylaxis, and adverse events. Results: Fifty-eight studies were evaluated. Apomorphine administration route was subcutaneous in 29 (50%), sublingual in 14 (24.1%), intranasal in 6 (10.3%), inhaled in 5 (8.6%), rectal in 3 (5.2%) and transdermal in 1 (1.7%). Irrespective of the route, motor disability improved 19% to 74% and daily off time decreased 3% to 68%, with subcutaneous having the fastest onset of action ranging from 6 to 24 minutes and lasting 28 to 96 minutes. Antiemetic prophylaxis was used in almost all studies. Systemic side effects like nausea and yawning were mild and well tolerated, but sedation led to discontinuation of subcutaneous apomorphine in 5.5%. Local side effects to subcutaneous administration did not result in discontinuation. Stomatitis with the early sublingual formulations led to discontinuation in nearly half of patients and was reduced to 16.7% with novel film strips. Conclusions: Intermittent subcutaneous injections remain the most reliable and safest route of apomorphine administration, with an efficacy for off period treatment supported by nearly four decades of clinical experience.

Non-tunneled catheter tip depth position in urgent hemodialysis: a randomized controlled trial.

BACKGROUND: The average accepted depth for non-tunneled catheters (NTC) insertion does not guarantee its correct position, so controversy exists. The aim of this study was to assess the effect of two NTC placement depths on the number of NTC complication episodes. METHODS: We designed a triple blind, parallel group, randomized controlled trial in a single Hemodialysis Center in Mexico (Registry: ACTRN12619000774123). We included patients in urgent need of hemodialysis via internal right jugular vein NTC. The length of the NTC tip placement depth was randomized to second intercostal space (2ICS) or fourth intercostal space (4ICS), using physical landmarks. The primary outcome was to compare the composite number of NTC dysfunction, repositioning, and relocation episodes for 48 hours post-procedure. RESULTS: One hundred and sixty-five patients were included, 86 and 79 patients to NTC placement in the 2ICS and 4ICS, respectively. All patients underwent intention-to-treat analysis. The incidence of the composite outcome was lower in the 2ICS group compared to the 4ICS group, 4 (4.6%) and 50 (63%) combined episodes, respectively (P<0.001). Compared to the 4ICS group, the 2ICS group presented a relative risk of 0.06 (CI: 0.02-0.21, P<0.001) and number needed to treat (NNT) of 2.1. No adverse events occurred, derived from the NTC placement. CONCLUSIONS: NTC tip placement in the 2ICS compared to 4ICS decreases the incidence of the combined number of dysfunctions, repositioning and relocation episodes, with a NNT of 2 for its prevention.

Early motor response to dopamine replacement therapy in Parkinson's disease patients carrying GBA variants.

BACKGROUND: Mutations in the glucocerebrosidase (GBA) gene represent the most common genetic risk factor for Parkinson's Disease (PD) and are associated with a more aggressive motor phenotype at late stages. However, the motor response at early stages of disease remains understudied. METHODS: Retrospective study of PD patients that underwent next-generation sequencing panel tests for PD-related genes. We extracted demographic data and the MDS-UPDRS III response to an acute levodopa challenge (LDC), the best ON score, and the levodopa equivalent daily dose (LEDD) during the first six months after the LDC and initiation of DRT. We compared the response of GBA-PD patients to that of patients without pathogenic variants or rearrangements in other PD related genes (sporadic PD). RESULTS: 13 GBA-PD and 48 sporadic PD patients were identified. Baseline MDS-UPDRS III score (24.6 ± 9.6 vs. 21.8 ± 9.3. p = 0.4), response to LDC (39.2% ± 7.9% vs. 32.7% ± 13.4%; p = 0.1), best ON score (36.9% ± 39.5% vs. 41.6% ± 20.8%; p = 0.6) and LEDD (188 mg ± 100 mg vs. 261.8 mg ± 164.8 mg; p = 0.2) during the first six months after initiation of DRT were not different between GBA-PD and sporadic PD patients. CONCLUSIONS: At early disease stages of GBA-PD, the motor response to acute levodopa challenge test and the initial response to DRT are similar to that of patients with sporadic PD. Although limited by small sample size, these preliminary findings should be confirmed by future prospective larger studies.

Eight-and-a-half syndrome: video evidence and updated literature review.

The eight-and-a-half syndrome (EHS)-defined by the combination of a seventh cranial nerve palsy and an ipsilateral one-and-a-half syndrome-is a rare brainstem syndrome, which localises to the caudal tegmental region of the pons. We present a case of the EHS secondary to an inflammatory lesion on a previously healthy 26-year-old woman, with a literature review emphasising the relevance of aetiological assessment.

Case of neuromyelitis optica: bilateral sensorineural hearing loss and transverse myelopathy following intrathecal chemotherapy.

Neurotoxicity from intrathecally administered chemotherapeutic drugs is frequent, particularly with some agents like methotrexate, which are more prone to developing adverse effects. Myelopathy ranks among the most frequently reported neurological entities; with the diagnosis being straightforward, after ruling out infectious, metabolic, autoimmune or paraneoplastic causes. Scarcity of cases precludes evidence-based recommendations for the management of these complications. The most common therapeutic approach consists of the suspension of chemotherapy, exclusion of infectious and neoplastic causes, with prompt administration of high-dose steroids. We report a 21-year-old patient with acute lymphoblastic leukaemia, who developed acute transverse myelitis and bilateral sensorineural hearing loss, after five rounds of intrathecal methotrexate and cytarabine. Although neurotoxicity from both agents has been documented, this combination has not been previously reported.

The poor insane Ophelia: reconsidering Ophelia syndrome.

INTRODUCTION: The association between memory loss and Hodgkin's lymphoma has been given the eponym of Ophelia syndrome, in memory of Shakespeare's character in The Tragedy of Hamlet, Prince of Denmark. Nevertheless, there are differences between the disease and the character. OBJECTIVE: To review the origins and uses of the eponym through an original article by pathologist Ian Carr, its relation to the character Ophelia, and the related autoantibodies. METHODS: Historical narrative review. RESULTS: Besides an eloquent description in the original article, Carr presaged the presence of autoantibodies, before they had been thoroughly researched. Since then, five different autoantibodies (mGluR5, Hu, NMDAR, SOX, PCA2) have been associated with Hodgkin's disease. It is interesting to note the divergent outcomes of Shakespeare's character and the patient in the original description by Carr, the latter recovering to lead a normal life, and the former deceased. CONCLUSIONS: Although there is little relationship between the fictional character and the syndrome, both imply the unintentional trigger of self-harm (suicide in one case, autoimmunity in the other), thus remaining associated.

Sir William Osler's 'Influences' for the Successful Physician, A Reappraisal After 126 Years.

BACKGROUND: The vertiginous pace with which modern medicine advances, can seem overwhelming to students and young doctors. AIM OF THE STUDY: To reappraise an oration by William Osler delivered to medical students at the point of their graduation. METHODS: Narrative review. RESULTS: Osler emphasised the Art of Detachment, the Virtue of Method, the Quality of Thoroughness and the Grace of Humility, which he considers the basic pillars on which a successful medical practice is achieved, Osler's words serve as a guiding light for physicians struggling with the demands of twenty first century medicine.