Longitudinal 16-year study of dominant intermediate CMT type C neuropathy.

BACKGROUND: Dominant-intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) is associated with mutations in the YARS gene. The aim of this study is to investigate the long-term natural history of the disease. METHODS: In a 5-generation DI-CMTC family, we compared data from 2016 to that of 2000 in 13 of 21 original participants. RESULTS: Five women and 8 men were examined. While most symptoms and signs progressed, only gait progression was statistically significant (P = .016). The median CMT Neuropathy Score was 6.08 in 2000 and 11 in 2016 (P = .001). Quality of life (QOL) deteriorated in mobility (P = .008), pain/discomfort (P = .011), and anxiety/depression (P = .014). Median and ulnar compound muscle action potential amplitudes decreased from 9.35 ± 2.90 mV to 6.0 ± 2.9 mV (P = .002), and from 9.24 ± 2.10 mV to 6.06 ± 1.81 mV (P = .004), respectively, whereas motor nerve conduction velocities remained unchanged. CONCLUSIONS: DI-CMTC in this family is a slowly progressive disease with axonal degeneration, deteriorating mobility and QOL.

Medical and neuropsychiatric phenomena depicted in two Spanish medieval texts of Marian miracles.

In the history of Christianity, veneration of the Virgin Mary reached its greatest intensity in the XIII century. Her perceived impact on daily life was tremendous and not surprisingly this extended to the spheres of disease and healing. The purpose of this study is to compare the medical and neuropsychiatric findings in two XIII century Spanish texts of Marian miracles, both examples of the popular Catholicism (vs. official catholic doctrine). We analyzed the medical and neuropsychiatric events in the Cantigas de Santa Maria (Canticles of St. Mary, CSM), composed at the court of Alfonso X and the Milagros de Nuestra Señora (The Miracles of Our Lady, MNS), written by Gonzalo de Berceo. Among the 25 miracles reported in the MNS, medically relevant facts were addressed in 19 miracles with a total of 23 recorded events (including resurrection or escape from death in five) and demonic possession in three (one with witchcraft/deicide). The most common medical subjects were ergotism, obstetric-gynecological, sudden death, intellectual disability/illiteracy, encephalopathy/alcohol intoxication, suicide (with self-mutilation/castration), infanticide, infections, and absence of body decomposition after death. The 427 canticles in the CSM contain 270 medically relevant facts. Neuropsychiatric conditions were alluded to in 98 songs. Blindness and dystonia/weakness/deformities were the most common phenomena. Illuminations detailed many of the medical facts in the CSM, but not in the MNS. Medically relevant facts were described in both texts, but with more details in the CSM. Neurological conditions were more often described in the CSM, psychiatric conditions in the MNS.

Chronic herpes simplex type-1 encephalitis with intractable epilepsy in an immunosuppressed patient.

BACKGROUND: Chronic herpes simplex virus type-1 encephalitis (HSE-1) is uncommon. Past reports focused on its association with prior documented acute infection. Here, we describe a patient with increasingly intractable epilepsy from chronic HSE-1 reactivation without history of acute central nervous system infection. CASE PRESENTATION: A 49-year-old liver transplant patient with 4-year history of epilepsy after initiation of cyclosporine developed increasingly frequent seizures over 3 months. Serial brain magnetic resonance imaging showed left temporoparietal cortical edema that gradually improved despite clinical decline. Herpes simplex virus type-1 (HSV-1) DNA was detected in cerebrospinal fluid by polymerase chain reaction. Cerebrospinal fluid HSV-1&2 IgM was negative. Seizures were controlled after acyclovir treatment, and the patient remained seizure free at 1-year follow-up. CONCLUSION: Chronic HSE is a cause of intractable epilepsy, can occur without a recognized preceding acute phase, and the clinical course of infection may not directly correlate with neuroimaging changes.

Pathological laughter and crying: A case series and proposal for a new classification.

BACKGROUND: Disorders of laughter and crying (DLC) are seen in several neuropsychiatric conditions. Their nomenclature remains under debate. METHODS: We present the clinical and imaging findings of 17 patients with DLC and introduce a new classification based on phenomenology and pathogenesis. According to intensity and frequency of laughter and crying (observed behavioral output), patients were divided into hypoactive or hyperactive DLC and subdivided into 5 subtypes: sensory (positive and negative), motor (positive and negative), and mixed. The sensory subtype is represented by disorders of "feeling processing," whereas the motor subtype is represented by disorders of "emotion processing." "Positive" and "negative" describe elicitation by irritative vs destructive lesions, respectively. RESULTS: Among the patients studied, DLC resulted from ischemic stroke (n = 12), intracerebral hemorrhage (n = 2), gunshot wound (n = 1), amyotrophic lateral sclerosis (n = 1), or vestibular migraine (n = 1). Ten patients had lesions in the brainstem, 4 in the cerebral hemispheres, and 2 in sub-cortical-diencephalic structures. Six patients had negative motor DLC, 5 had positive sensory DLC, 4 had negative sensory DLC, and 2 had positive motor DLC. Phenomenology changed or progressed to mixed DLC in 7 patients. CONCLUSIONS: This novel phenomenological and pathomechanistic nomenclature explains all subtypes of DLC in neurologic, medical, and psychiatric conditions. Future studies are needed to validate it prospectively.

Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.

Charcot-Marie-Tooth (CMT) neuropathies are common disorders of the peripheral nervous system caused by demyelination or axonal degeneration, or a combination of both features. We previously assigned the locus for autosomal dominant intermediate CMT neuropathy type C (DI-CMTC) to chromosome 1p34-p35. Here we identify two heterozygous missense mutations (G41R and E196K) and one de novo deletion (153-156delVKQV) in tyrosyl-tRNA synthetase (YARS) in three unrelated families affected with DI-CMTC. Biochemical experiments and genetic complementation in yeast show partial loss of aminoacylation activity of the mutant proteins, and mutations in YARS, or in its yeast ortholog TYS1, reduce yeast growth. YARS localizes to axonal termini in differentiating primary motor neuron and neuroblastoma cultures. This specific distribution is significantly reduced in cells expressing mutant YARS proteins. YARS is the second aminoacyl-tRNA synthetase found to be involved in CMT, thereby linking protein-synthesizing complexes with neurodegeneration.

Relation of Demographics and Reported Symptoms and Medication Use in Persons with Multiple Sclerosis.

A study using a cross-sectional descriptive design examined symptoms, race, sex, and use of disease-modifying therapies (DMT) in persons with relapsing remitting multiple sclerosis. Significant differences in symptoms and DMT use were found among women, men, and African Americans.

Comparing multicomponent interventions to improve skin care behaviors and prevent recurrence in veterans hospitalized for severe pressure ulcers.

OBJECTIVE: To compare a multicomponent motivational interviewing (MI)/self-management (SM) intervention with a multicomponent education intervention to improve skin-protective behaviors and prevent skin worsening in veterans with spinal cord injury (SCI) hospitalized for severe pressure ulcers (PrUs). DESIGN: Single-blinded, prospective, randomized controlled trial. SETTING: Six Veterans Affairs SCI centers. PARTICIPANTS: Veterans admitted for a severe (stage III/IV) PrU were followed up to 6 months postdischarge. INTERVENTION: Telephone-based individual MI counseling plus SM skills group (SM+MI; n=71) versus an active control group of telephone-based individual educational counseling plus group education (n=72). MAIN OUTCOME MEASURES: Self-reported skin-protective behaviors, objective skin worsening. RESULTS: Intention-to-treat analyses found nonsignificant increases in skin behaviors in the SM+MI versus education control intervention arms at 3 and 6 months. The difference in behaviors used between SM+MI and education control intervention participants was 4.6% (95% confidence interval [CI], -11.3 to 2.7) (0-3mo) and 3.0% (95% CI, -8.7 to 3.9) (0-6mo). High rates of skin worsening were observed (n=74, 51.7%), usually within 3 months postdischarge and most frequently within the month postdischarge. Skin worsening, skin-related visits, and readmissions did not differ by study arm. Study limitations are presented. CONCLUSIONS: For persons with chronic SCI and severe PrUs, complicated by multiple comorbidities, a primary focus on improving patient behavior is likely insufficient to address the complex problem of PrUs in SCI. More health care systems-level changes such as collaborative care may be needed to reduce PrU recurrence, especially in this era in which many people are discharged from the hospital unhealed or with little sitting tolerance.

Custom order entry for Parkinson's medications in the hospital improves timely administration: an analysis of over 31,000 medication doses.

Background: Patients with Parkinson's disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using "custom" ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital. Material and methods: We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed. Results: 14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group (p<.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p<0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time (p<0.001 for all comparisons). Conclusion: This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications.

Effectiveness of supported employment for veterans with spinal cord injuries: results from a randomized multisite study.

OBJECTIVE: To examine whether supported employment (SE) is more effective than treatment as usual (TAU) in returning veterans to competitive employment after spinal cord injury (SCI). DESIGN: Prospective, randomized, controlled, multisite trial of SE versus TAU for vocational issues with 12 months of follow-up data. SETTING: SCI centers in the Veterans Health Administration. PARTICIPANTS: Subjects (N=201) were enrolled and completed baseline interviews. In interventional sites, subjects were randomly assigned to the SE condition (n=81) or the TAU condition (treatment as usual-interventional site [TAU-IS], n=76). In observational sites where the SE program was not available, 44 subjects were enrolled in a nonrandomized TAU condition (treatment as usual-observational site [TAU-OS]). INTERVENTIONS: The intervention consisted of an SE vocational rehabilitation program called the Spinal Cord Injury Vocational Integration Program, which adhered as closely as possible to principles of SE as developed and described in the individual placement and support model of SE for persons with mental illness. MAIN OUTCOME MEASURES: The primary study outcome measurement was competitive employment in the community. RESULTS: Subjects in the SE group were 2.5 times more likely than the TAU-IS group and 11.4 times more likely than the TAU-OS group to obtain competitive employment. CONCLUSIONS: To the best of our knowledge, this is the first and only controlled study of a specific vocational rehabilitation program to report improved employment outcomes for persons with SCI. SE, a well-prescribed method of integrated vocational care, was superior to usual practices in improving employment outcomes for veterans with SCI.

Position-dependent arm dyskinesia due to severe craniocervical malformation.

CONTEXT: Spinal-generated movement disorders are a complex group of medical conditions, frequently misdiagnosed, originating in the spinal cord or from combined peripheral and central nervous system involvement. In this case report, we describe a novel form of position-dependent dyskinesia due to severe craniocervical malformation. FINDINGS: An 83-year-old woman with basilar invagination at the C2 vertebra above the line of Chamberlain, occipitocervical lordosis, platybasia with a short clivus, ankylosis of the C1-C2 complex and fusion of the C1 arch developed an unusual pattern of position-dependent left arm dyskinesia triggered by bending her neck forward with simultaneous contact of the flexed elbow with a flat surface. Symptoms did not improve with anticonvulsants and she progressed and died suddenly. CONCLUSION/CLINICAL RELEVANCE: A newly described form of position-dependent arm dyskinesia can be associated with severe craniocervical malformation.

Motor Cortex Response to Pleasant Odor Perception and Imagery: The Differential Role of Personality Dimensions and Imagery Ability.

Background: Neuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil (BEO) is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor (BEO) on motor cortex using Transcranial magnetic stimulation (TMS). Materials and Methods: We examined the primary motor cortex (M1) excitability during perception of a pleasant odor (BEO) or perception of odorless saline (experiment 1). Furthermore, we tested the effect of olfactory imagery (OI) of BEO on corticospinal excitability (experiment 2). The increase in motor evoked potential (MEP) amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability. Results: The results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor (BEO). The correlation analysis shows an association with neuroticism personality trait (experiment 1) and with general olfactory imagery ability (experiment 2). Conclusion: Both perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems.

Patient-Reported Symptom Burden of Charcot-Marie-Tooth Disease Type 1A: Findings From an Observational Digital Lifestyle Study.

OBJECTIVES: This study aims to explore the impact of Charcot-Marie-Tooth disease type 1A (CMT1A) and its treatment on patients in European (France, Germany, Italy, Spain, and the United Kingdom) and US real-world practice. METHODS: Adults with CMT1A (n = 937) were recruited to an ongoing observational study exploring the impact of CMT. Data were collected via CMT&Me, an app through which participants completed patient-reported outcome measures. RESULTS: Symptoms ranked with highest importance were weakness in the extremities, difficulty in walking, and fatigue. Almost half of participants experienced a worsening of symptom severity since diagnosis. Anxiety and depression were each reported by over one-third of participants. Use of rehabilitative interventions, medications, and orthotics/walking aids was high. CONCLUSIONS: Patient-reported burden of CMT1A is high, influenced by difficulties in using limbs, fatigue, pain, and impaired quality of life. Burden severity appears to differ across the population, possibly driven by differences in rehabilitative and prescription-based interventions, and country-specific health care variability.

Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease.

OBJECTIVE: To determine whether locally acting ACE-083 is safe, well tolerated, and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1. METHODS: This phase 2 study enrolled adults with CMT1 or CMTX (N=63). Part 1 was open-label and evaluated safety and tolerability of different dose levels of ACE-083 for use in Part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally in the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-meter walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests. RESULTS: In Part 1 (n=18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious AEs, TEAEs ≥Grade 3, or death reported. In Part 2 (n=45 enrolled, n=44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (LS mean difference: 13.5%; p = 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate-to-mild injection-site reactions were the most common TEAEs. CONCLUSIONS: Despite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that intramuscular ACE-083 is safe, well tolerated, and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.

Acute social and somatic stress alters cortical metaplasticity probed with non-invasive brain stimulation in humans.

Studying the neuronal mechanisms that govern the cortical adaptations to acute stress is critical for understanding the development of neuropsychiatric diseases. Homeostatic plasticity stabilizes the neural activity in which a previous synaptic event drives subsequent synaptic plasticity. In this study, we evaluated the effect of acute stress induced with the socially evaluated cold pressor test (SECPT) on cortical metaplasticity in humans using a non-invasive brain stimulation protocol. After being exposed to the SECPT and control stress conditions, 30 healthy participants were tested for cortical metaplasticity assessed with changes in the amplitude of the motor evoked potential (MEP) induced by a single-pulse transcranial magnetic stimulation (TMS). Cortical metaplasticity was induced by combining priming with cathodal tDCS (cTDCS) followed by a sub-threshold 1-Hz repetitive stimulation (rTMS) test session. Our results showed that SECPT induced cardiovascular adaptations (increase in systolic, diastolic blood pressure, and heart rate), indicating that SECPT effectively induced acute stress. Also, in our experiments stimulation of subjects with 1-Hz rTMS after they had undergone the SECPT condition induced inhibition of MEP whereas 1-Hz rTMS administered after the control condition induced a facilitatory (physiologic) response pattern. Here we observed that acute stress impairs homeostatic metaplasticity. The dysfunctional regulation of cortical plastic changes after stress could play a pivotal role in the pathogenesis of neurological and psychiatric diseases.

Improving Sleep among Adults with Multiple Sclerosis using Mindfulness plus Sleep Education.

We explored the feasibility of a mindfulness plus sleep education intervention, SleepWell!, delivered via videoconference compared to onsite among adults with MS. A non-randomized wait-list control design was used. Participants wore actigraphy watches and kept sleep diaries for seven days pre- and post intervention. Questionnaires were completed pre-intervention, post-intervention, and three months post-intervention. One group was conducted onsite. Three groups participated via videoconference. Attrition among videoconference groups was 23% compared to 57% in the onsite group. Within group analysis showed moderate-to-large effect sizes on sleep efficiency (d=0.78) and total sleep time (d=0.54) in the videoconference groups. One-way repeated measures ANOVA post-hoc analysis suggested small-to-medium effect over three months on sleep quality (ηp2 =0.28), physical health quality of life (ηp2 =0.42), mental health quality of life (ηp2 =0.13), and mindfulness (ηp2 =0.29). Results indicate feasibility of providing our intervention via videoconferencing. Preliminary analysis suggests that SleepWell! improves sleep and mindfulness among adults with MS.

A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is a rare, orphan, hereditary neuromuscular disorder with no cure and for which only symptomatic treatment is currently available. A previous phase 2 trial has shown preliminary evidence of efficacy for PXT3003 in treating CMT1A. This phase 3, international, randomized, double-blind, placebo-controlled study further investigated the efficacy and safety of high- or low-dose PXT3003 (baclofen/naltrexone/D-sorbitol [mg]: 6/0.70/210 or 3/0.35/105) in treating subjects with mild to moderate CMT1A. METHODS: In this study, 323 subjects with mild-to-moderate CMT1A were randomly assigned in a 1:1:1 ratio to receive 5 mL of high- or low-dose PXT3003, or placebo, orally twice daily for up to 15 months. Efficacy was assessed using the change in Overall Neuropathy Limitations Scale total score from baseline to months 12 and 15 (primary endpoint). Secondary endpoints included the 10-m walk test and other assessments. The high-dose group was discontinued early due to unexpected crystal formation in the high-dose formulation, which resulted in an unanticipated high discontinuation rate, overall and especially in the high-dose group. The statistical analysis plan was adapted to account for the large amount of missing data before database lock, and a modified full analysis set was used in the main analyses. Two sensitivity analyses were performed to check the interpretation based on the use of the modified full analysis set. RESULTS: High-dose PXT3003 demonstrated significant improvement in the Overall Neuropathy Limitations Scale total score vs placebo (mean difference: - 0.37 points; 97.5% CI [- 0.68 to - 0.06]; p = 0.008), and consistent treatment effects were shown in the sensitivity analyses. Both PXT3003 doses were safe and well-tolerated. CONCLUSION: The high-dose group demonstrated a statistically significant improvement in the primary endpoint and a good safety profile. Overall, high-dose PXT3003 is a promising treatment option for patients with Charcot-Marie-Tooth disease type 1A.

Patient-reported impact of Charcot-Marie-Tooth disease: protocol for a real-world digital lifestyle study.

Charcot-Marie-Tooth disease (CMT) is a rare, chronic, progressive motor and sensory neuropathy affecting the peripheral nervous system. This study will explore the real-world impact of CMT. The trial is a digital study of approximately 2000 people in 6 countries with CMT ≥18 years. Participants will use a smartphone application to check eligibility, provide consent and contribute data. The dataset will include a personal profile, covering demographics, lifestyle, diagnosis and treatment and a selection of validated generic and disease-specific instruments. Participants will provide data for up to 2 years. Data analysis will be conducted upon registration of the 1000th participant and at 12-month intervals from launch. This study is designed to help researchers and clinicians understand the real-world impact of CMT and the unmet needs of patients. ClinicalTrials.gov identifier: NCT03782883.

Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis.

Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease of the lower and upper motor neurons with sporadic or hereditary occurrence. Age of onset, pattern of motor neuron degeneration and disease progression vary widely among individuals with ALS. Various cellular processes may drive ALS pathomechanisms, but a monogenic direct metabolic disturbance has not been causally linked to ALS. Here we show SPTLC1 variants that result in unrestrained sphingoid base synthesis cause a monogenic form of ALS. We identified four specific, dominantly acting SPTLC1 variants in seven families manifesting as childhood-onset ALS. These variants disrupt the normal homeostatic regulation of serine palmitoyltransferase (SPT) by ORMDL proteins, resulting in unregulated SPT activity and elevated levels of canonical SPT products. Notably, this is in contrast with SPTLC1 variants that shift SPT amino acid usage from serine to alanine, result in elevated levels of deoxysphingolipids and manifest with the alternate phenotype of hereditary sensory and autonomic neuropathy. We custom designed small interfering RNAs that selectively target the SPTLC1 ALS allele for degradation, leave the normal allele intact and normalize sphingolipid levels in vitro. The role of primary metabolic disturbances in ALS has been elusive; this study defines excess sphingolipid biosynthesis as a fundamental metabolic mechanism for motor neuron disease.

Associations Between Self-Reported Symptoms and Gait Parameters Using In-Home Sensors in Persons With Multiple Sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a progressive neurological disorder, characterized by exacerbations and remissions, often resulting in disability affecting multiple neurological functions. The purpose of this article was (1) to describe the frequencies of self-reported symptoms in a natural environment and (2) to determine characteristics and associations between self-reported symptoms and home gait parameters (speed, stride time, and stride length) at baseline and at 3 months in patients with MS. METHODS: Participants completed the self-report MS-Related Symptom Scale to measure symptoms. A three-dimensional depth imaging system (Foresite Healthcare) was used to measure gait parameters in the home environment. RESULTS: These data show significant correlations between the following symptoms: knee locking or collapsing, difficulty sleeping, depression, and anxiety with decreased number of average walks per day; however, the symptoms including trouble-making toilet: day and difficulty in starting urine were positively correlated with average walks per day. The symptom numbness was significantly correlated with decreased speed and decreased stride length. DISCUSSION AND CONCLUSIONS: Our findings suggest that certain groups of symptoms were more frequently reported with certain gait parameters (stride time/speed) in persons with MS. Rehabilitation nurses can provide optimal care to prevent future decline in symptoms and gait.