Bacterial Lipopolysaccharides Exacerbate Neurogenic Heterotopic Ossification Development.

Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer concomitant infections. However, it is unclear whether these infections directly contribute to NHO development or reflect the immunodepression observed in patients with CNS injury. Using our mouse model of NHO induced by spinal cord injury (SCI) between vertebrae T11 to T13 , we demonstrate that lipopolysaccharides (LPS) from gram-negative bacteria exacerbate NHO development in a toll-like receptor-4 (TLR4)-dependent manner, signaling through the TIR-domain-containing adapter-inducing interferon-ß (TRIF/TICAM1) adaptor rather than the myeloid differentiation primary response-88 (MYD88) adaptor. We find that T11 to T13 SCI did not significantly alter intestinal integrity nor cause intestinal bacteria translocation or endotoxemia, suggesting that NHO development is not driven by endotoxins from the gut in this model of SCI-induced NHO. Relevant to the human pathology, LPS increased expression of osteoblast markers in cultures of human fibro-adipogenic progenitors isolated from muscles surrounding NHO biopsies. In a case-control retrospective study in patients with traumatic brain injuries, infections with gram-negative Pseudomonas species were significantly associated with NHO development. Together these data suggest a functional association between gram-negative bacterial infections and NHO development and highlights infection management as a key consideration to avoid NHO development in patients. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients.

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off-label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually. The noncompartmental pharmacokinetic study of atropine performed in 1 patient highlighted that systemic absorption of sublingual atropine was effective (Cmax [1 h] = 2.2 ng mL-1 ; approximately) after a single dose of 1 mg.

Early diagnosis of heterotopic ossification among patients admitted to a neurological Post-Intensive Care Rehabilitation Unit.

BACKGROUND: Heterotopic ossification (HO) is defined as the formation of endochondral bone within soft tissue. Non-genetic forms, mainly corresponding to a consequence of bone, brain or spinal cord injury, are the most common. HO leads to important functional limitations and alteration of quality of life. To our knowledge, the time between brain, bone, or spinal cord injury and clinical suspicion of HO has never been studied. By admitting patients with severe neurological disorders, we hypothesized that the prevalence of HO in neurological post-intensive care rehabilitation units (PICRU) might be significant as these patients have recognized risk factors for HO. AIM: This study aimed to investigate HO among patients admitted to a neurological PICRU with two objectives: 1) to describe the prevalence of HO in PICRU; 2) to assess the time between neurological disorder, clinical suspicion of HO and radiological diagnosis. DESIGN: A monocentric retrospective cohort study. SETTING: PICRU in our public university teaching hospital. This inpatient referral department is specifically dedicated to the early discharge from Intensive Care Units (ICU) of patients with severe neurological impairment who need rehabilitation. POPULATION: We study all patients admitted between April 2016 and January 2019. One hundred twenty-five subjects were admitted for a rehabilitation program after neuro-trauma or stroke. We included all first-time stays in PICRU lasting 7 days or longer. METHODS: Retrospective data extraction using administrative data from an electronic patient management program was done to select eligible subjects. Included subjects were then identified by a retrospective review of electronic inpatient medical records after patient discharge. Data of interest were collected from these same medical records. RESULTS: Forty-four HO were diagnosed in 24 subjects (24/125; 19%), with a median number of 2 [1; 2] HO per subject. Neurological trauma was the main reason for admission to ICU (89/125; 71%) and half of patients had a traumatic brain injury (TBI) (67/125; 54%). The diagnosis of HO was made in PICRU in 75% of cases. Clinical suspicion of HO (autonomic dysfunction, local inflammatory signs, pain, or reduced joint range of motion) was made 6 [5; 7] weeks after admission to ICU. Radiological confirmation of clinical suspicion or fortuitous diagnosis by imaging (50% of the cases) occurred 8 [7; 12] weeks after admission to ICU. The median time of clinical suspicion or radiological diagnosis was 1 week after admission to PICRU. CONCLUSIONS: HO is a sub-acute complication which develops in patients admitted to ICU for severe central nervous system disorders as clinical suspicion or radiological confirmation of diagnosis was made within the first week after admission in neurological PICRU (i.e. 6 to 8 weeks after ICU admission). CLINICAL REHABILITATION IMPACT: As treatment for HO may at least partially improves rehabilitation and quality of life, we recommend a systematic screening in PICRU patients for HO by clinical examination supplemented by imaging in case of suspicion.

Unexpected good outcome in severe cerebral fat embolism syndrome.

In this case study, we report the longitudinal and multimodal follow-up of a catastrophic initial presentation of cerebral fat embolism syndrome. We show that despite the initial severity, the cognitive outcome was ultimately very good but with a highly nonlinear time-course and prolonged loss of consciousness (more than 2 months). Repeated clinical assessments and brain-imaging techniques (electroencephalography, event-related potential, 18-Fluoro-Deoxy-Glucose-PET and magnetic resonance imaging) allowed us to monitor and anticipate this dynamic, providing relevant information to guide decision making in front of withdrawal of life-sustaining therapy discussions. This case illustrates the value of multimodal functional imaging in devastating brain injuries.

Subjective complaints after acquired brain injury: presentation of the Brain Injury Complaint Questionnaire (BICoQ).

The objective of the present study was to present a new complaint questionnaire designed to assess a wide range of difficulties commonly reported by patients with acquired brain injury. Patients (n = 619) had been referred to a community re-entry service at a chronic stage after brain injury, mainly traumatic brain injury (TBI). The Brain Injury Complaint Questionnaire (BICoQ) includes 25 questions in the following domains: cognition, behavior, fatigue and sleep, mood, and somatic problems. A self and a proxy questionnaire were given. An additional question was given to the relative, about the patient's awareness of his difficulties. The questionnaires had a good internal coherence, as measured with Cronbach's alpha. The most frequent complaints were, in decreasing order, mental slowness, memory troubles, fatigue, concentration difficulties, anxiety, and dual tasking problems. Principal component analysis with varimax rotation yielded six underlying factors explaining 50.5% of total variance: somatic concerns, cognition, and lack of drive, lack of control, psycholinguistic disorders, mood, and mental fatigue/slowness. About 52% of patients reported fewer complaints than their proxy, suggesting lack of awareness. The total complaint scores were not significantly correlated with any injury severity measure, but were significantly correlated with disability and poorer quality of life (Note: only factor 2 [cognition/lack of drive] was significantly related to disability.) The BICoQ is a simple scale that can be used in addition to traditional clinical and cognitive assessment measures, and to assess awareness of everyday life problems.

Ceftolozane/tazobactam for febrile UTI due to multidrug-resistant Pseudomonas aeruginosa in a patient with neurogenic bladder.

INTRODUCTION: Urinary tract infections (UTI) are a major public health problem among spinal cord injury (SCI) patients. They frequently involve multidrug-resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic combination approved for complicated intra-abdominal and UTI caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for complicated febrile UTI occurring among SCI patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). CASE PRESENTATION: We describe the case of a 35-year-old man with SCI due to multiple sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and double J catheter, who developed a febrile UTI due to a MDR PSA, which was susceptible only to amikacin and colistin. Because of this MDR phenotype and the underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin. Thanks to this treatment, the patient had a favorable outcome with no clinical signs of UTI or positive urine culture up to 1 month after diagnosis. DISCUSSION: C/T seems to be an effective and safe therapeutic option for febrile UTI due to MDR PSA in SCI patients with neurogenic bladder, even when administered in monotherapy for 10 days.

Construction and pilot assessment of the Lower Limb Function Assessment Scale.

BACKGROUND: Stroke often leads to upright standing and walking impairments. Clinical assessments do not sufficiently address ecological aspects and the patient's subjective evaluation of function. OBJECTIVE: To perform a pilot assessment of the psychometric properties of the Lower Limb-Function Assessment Scale (LL-FAS). METHODS: The LL-FAS includes 30 items assessing the patient's perception (in a questionnaire) and the examiner's perception (in a practical test) of upright standing and walking impairments and their impact on activities of daily living. We analyzed the LL-FAS's reliability, construct validity, internal consistency, predictive validity and feasibility. RESULTS: Thirty-five stroke patients were included. The scale's mean ± SD completion time was 25 ± 6 min. Intra-observer reliability was good to excellent (intraclass correlation coefficients (ICC >0.82). Interobserver reliability was moderate (0.67 < ICC < 0.9). The questionnaire and test items showed excellent construct validity for neuromotor disabilities (p < 0.05), postural ability (Postural Assessment Scale for Stroke; p < 10-5), severity of gait disorders (Gait Assessment and Intervention Tool; p < 10-3), walking ability (New Functional Ambulation Categories, 10 m walk test, Rivermead Mobility Index; p < 10-3) and functional level (Barthel Index; p < 10-3). Internal consistency (Cronbach-α >0.9) and predictive validity were excellent. CONCLUSIONS: The LL-FAS showed fair psychometric properties in this pilot study and may be of value for evaluating post-stroke lower limb impairment.

The long-term nutritional status in stroke patients and its predictive factors.

BACKGROUND: Malnutrition is common in the first few months after stroke and contributes to a poor overall outcome. We analyzed long-term weight changes and their predictive factors. METHODS: A total of 71 first-ever stroke patients were included in the study and examined (1) their weight on admission to the acute stroke unit (usual weight [UW]), on admission to the rehabilitation unit, on discharge from the rehabilitation unit, and then 1 year or more after the stroke (median time: 2.5 years), (2) the presence of malnutrition after stroke, and (3) possible predictive factors, namely, sociodemographic factors, clinical characteristics (concerning the stroke, the patient's current neurologic status and the presence of diabetes mellitus and depression), and the present nutritional state (including eating difficulties, anorexia, and changes in food intake and food preferences). RESULTS: Body weight fell (4.0 kg) during the patients' stay in the stroke unit, increased moderately in the rehabilitation unit (2.0 kg), and returned to the UW by the long-term measurement. However, at the last observation, 40.1% of the patients weighed markedly less than their UW, 38.0% weighed markedly more, and 21.1% were relatively stable. Predictors of weight change were a change in preferences for sweet food products and a change in food intake. Malnutrition was frequent (47.9%) and associated with reduced food intake, residence in an institution, and diabetes mellitus. CONCLUSIONS: Malnutrition was highly prevalent, with an important role of change in food intake and food preferences, which could result from brain lesions and specific regimens. Living in an institution needs consideration, as its negative effects can be prevented.