Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

PURPOSE: Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. METHODS: All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. RESULTS: Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). CONCLUSION: Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

Risk factors associated with colonic diverticulosis among patients from a defined geographic area.

BACKGROUND: Only a few data regarding colonic diverticulosis are available in Italy. We examined the frequency of colonic diverticulosis and its associations with risk factors in a homogeneous Northern Sardinian population undergoing colonoscopy for any reason in the last decades. METHODS: This was a retrospective single-center study. Medical records of patients undergoing colonoscopy for any indication between 1995 and 2013 were reviewed. Demographic information including age, gender, geographic area (urban, rural), marital status, smoking habit, occupation, body mass index, and comorbidities were collected. Presence, number, and extension of diverticula were assessed by colonoscopy. The diagnosis of diverticulosis was defined by the presence of more than five diverticula. RESULTS: A total of 4458 records were collected (39.8 % males). Analysis by birth cohorts showed a significant progressive age-related increase in the prevalence of diverticulosis. The average prevalence was 18.9 % without significant variation across the 19-year observation period. In 101 (12.1 %) subjects diverticula were single or few. Seventy-one percent of diverticula were located predominantly in the left side, 2 % in the right side, and 14.3 % were spread throughout the colon. There was a significant association with obesity but not with smoking habits, marital status, or urban versus rural environment. A strong association was observed between the presence of diverticulosis and cardiovascular and other gastrointestinal and lung disease (p < 0.0001). These associations were also confirmed by the logistic regression analysis. CONCLUSIONS: In this endoscopic study, colonic diverticulosis in Northern Sardinia showed prevalence similar to other series in Western countries, and it was predominantly left sided and age related.

The autonomic balance predicts cardiac responses after the first dose of fingolimod.

BACKGROUND: Predictive markers of cardiac side effects would be helpful for the stratification and individualized monitoring of multiple sclerosis (MS) patients prescribed with fingolimod. OBJECTIVE: To test whether the autonomic balance predicts a cardiac response after the first dose of fingolimod. METHODS: A total of 55 consecutive relapsing-remitting MS (RRMS) patients underwent 'head-up tilt', Valsalva maneuver, deep breathing and handgrip tests before their first dose of fingolimod. The normalized unit of the high frequency (HF) component (HF normalized units; HFnu), reflecting mostly vagal activity; and the low frequency (LF) component (LF normalized units; LFnu) reflecting mostly sympathetic activity, were considered for the analysis of heart rate (HR) variability. The patients' HR and electrocardiographic parameters ((the interval between P wave and ventricular depolarization (PR); the interval between Q and T waves (QT)) were recorded during 6-hour post-dose monitoring. RESULTS: We found significant correlations between measures of parasympathetic function and fingolimod-induced bradycardia. Subjects with higher Valsalva ratio and HR variation during deep breathing had, in fact, nadir HR ≤ 50 beats/minute (bpm) after the first fingolimod dose. Conversely, significant negative correlations were found between measures of sympathetic function and fingolimod-induced PR interval increase. Subjects with lower LFnu at rest and less increase of blood pressure on the handgrip test showed a PR interval increase > 20 ms after fingolimod. CONCLUSIONS: Assessing autonomic control of cardiovascular functions can be useful to predict cardiac effects after the first fingolimod dose.

Interleukin-8 is associated with acute and persistent dysfunction after optic neuritis.

BACKGROUND: Acute optic neuritis is often in association with multiple sclerosis (MS). Proinflammatory cytokines trigger neuronal damage in neuroinflammatory disorders but their role in optic neuritis is poorly investigated. OBJECTIVE: The objective of this work is to investigate the associations of intrathecal contents of proinflammatory cytokines with transient and persistent dysfunctions after optic neuritis. METHODS: In 50 MS patients followed for up to six months, cerebrospinal fluid (CSF) levels of IL-1ß, TNF and IL-8 were determined, along with clinical, neurophysiological and morphological measures of optic neuritis severity. RESULTS: Visual impairment, measured by high- and low-contrast visual acuity, and delayed visual-evoked potential (VEP) latencies were significantly correlated to IL-8 levels during optic neuritis. IL-8 at the time of optic neuritis was also associated with persistent demyelination and final axonal loss, inferred by VEP and optical coherence tomography measures, respectively. Contents of IL-8 were correlated to functional visual outcomes, being higher among patients with incomplete recovery. Multivariate analysis confirmed that IL-8 significantly predicted final visual acuity, at equal values of demographics and baseline visual scores. CONCLUSION: Our study points to IL-8 as the main inflammatory cytokine associated with demyelination and secondary neurodegeneration in the optic nerve after optic neuritis.

[Current status of French oculoplastics in France and in Europe]. / État des lieux de l'oculoplastie française en France et en Europe.

INTRODUCTION: In 2023, oculoplastics in France is experiencing a paradox with an imbalance between demand and supply of trainees. The goal of this study is to establish a factual overview of oculoplastics in France, with its limitations, and make proposals to optimize this sector. METHODS: An observational study was conducted by compiling epidemiological data related to oculoplastics. This included full-time hospital practitioners (HPs) in French university hospitals (FUH), data from the distributed computerized system for health assessment (SIDES), the specialized cross-disciplinary training (FST) in oculoplastics, the interuniversity diploma (DIU) in oculoplastics, the French University Ophthalmologists College (COUF), and the French Society of Reconstructive and Aesthetic Ophthalmology (SOPREF). RESULTS: Of the 32 FUH, only 11 full-time HPs (among them 5 academic) are specialized in oculoplastics. Several "priority" regions are underrepresented in oculoplastic surgeons. The number of ophthalmology residency coordinators and residents participating in the oculoplastics FST are decreasing over time and favoring other subspecialties. On the SIDES platform dedicated to residents, 26 (11.5%) of the 226 courses are devoted to oculoplastics. The role of women in oculoplastics is also discussed. CONCLUSION: Despite offering quality theoretical training, the future of French oculoplastics is clouded by a lack of practical training. Corrective measures include increasing oculoplastic surgeons in the FUH, developing private practice fellowships, prioritizing residents from "priority" regions for the oculoplastics DIU, optimizing the inter-CHU network, creating innovative teaching resources, and organizing specific congresses for the residents.

COVID-19: identifying the main outcome predictors. A retrospective cohort study in Northern Italy.

OBJECTIVE: The need for efficient drugs and early treatment of patients with SARS-CoV-2 infection developing COVID-19 symptoms is of primary importance in daily clinical practice and it is certainly among the most difficult medical challenges in the current century. Recognizing those patients who will need stronger clinical efforts could effectively help doctors anticipate the eventual need for intensification of care (IoC) and choose the best treatment in order to avoid worse outcomes. PATIENTS AND METHODS: We enrolled 501 patients, consecutively admitted to our two COVID hospitals, and collected their clinical, anamnestic and laboratory data on admission. The aim of this retrospective study was to identify those data that are strictly associated with COVID-19 outcomes (IoC and in-hospital death) and that could somehow be intended as predictors of these outcomes. This allowed us to provide a "sketch" of the patient who undergoes, more often than others, an intensification of care and/or in-hospital death. RESULTS: Males were found to have a double risk of needing an IoC (OR=2.11) and a significant role was played by both the PaO2/FiO2 ratio on admission (OR=0.99) and serum LDH (OR=1.01). The main predictors of in-hospital death were age (OR=1.08) and the PaO2/FiO2 ratio on admission (OR=0.99). CONCLUSIONS: Male patients with high serum LDH on admission are those who undergo more often an intensification of care among COVID-19 inpatients. Both age and respiratory performances on admission modify the prognosis within the hospitalization period.

Is there a correlation between urological and cardiovascular dysfunction in Parkinson's disease?

It is well established that non-motor symptoms are a core feature of Parkinson's disease (PD). A dysregulation of the autonomic nervous system seems to be present in PD, supporting the coexistence of urological and cardiovascular non-motor features. We evaluated whether bladder dysfunctions in patients with PD are linked to blood pressure dysregulation. Twenty-eight mild PD patients, previously submitted to a urodynamic evaluation, underwent 24-hour ambulatory blood pressure and heart rate monitoring to allow assessment of their circadian blood pressure profile; the occurrence of postprandial hypotension and orthostatic hypotension was also investigated. No significant differences in blood pressure control were detected between bladder hyperreflexic and normoreflexic subjects. Our findings support different origins of urological and cardiovascular impairments in PD.

Upper motor neuron involvement in X-linked recessive bulbospinal muscular atrophy.

OBJECTIVE: Clinicopathological findings of X-linked recessive bulbospinal muscular atrophy (SBMA) are indicative of lower motor neuron and primary sensory neuron involvement. The aim of our study was to investigate the presence of subclinical upper motor neuron (UMN) dysfunction in this disease. METHODS: Two siblings with clinical presentation, routine electrophysiological tests, histopathological features of muscle and nerve biopsies and genetic testing consistent with diagnosis of SBMA underwent transcranial magnetic stimulation (TMS). The analysed parameters were motor evoked potential (MEP) threshold, silent period (SP) and central motor conduction time. Intracortical inhibition with paired pulses from 1 to 6ms interstimulus intervals (ISIs) was evaluated in the older brother. RESULTS: MEP parameters were significantly altered in limb and cranial muscles and MEP suppression after paired stimulation significantly reduced in the older brother. MEP abnormalities were present in one lower limb, but SP abolished in all limbs, in the younger brother. CONCLUSIONS: Subclinical involvement of UMNs may be present in patients affected by SBMA. This finding suggests that the array of neuronal systems whose function may be affected by the pathogenic process of SBMA is larger than it was considered so far. SIGNIFICANCE: TMS is a sensitive diagnostic tool for the identification of UMN dysfunction and should be included in the diagnostic evaluation of patients with SBMA.

A comparative study of free amino acids in coma of different aetiologies.

A comparative study of the concentrations of free amino acids in the plasma and cerebrospinal fluid in cases of coma of different origins has been made. Hypotheses are put forward to explain the biochemical steps involved in cerebral metabolism of protein.

Free amino acids in plasma and erythrocytes during and after cardiopulmonary by-pass in open-heart surgery.

The concentrations in plasma and erythrocytes of free amino acids before, during and after cardiopulmonary by-pass have been determined. During by-pass and the early postoperative period the total alpha-amino nitrogen decreased, mainly because of changes in glucogenic amino acids; ketogenic amino acids, on the other hand, increased. The phenylalanine/tyrosine ratio was markedly increased in all cases.

Intravenous sodium lactate administration in respiratory alkalosis secondary to severe brain injuries.

In acute cerebrovascular accidents the uptake of lactate by the brain tissue is enhanced, possibly in an attempt to buffer the increased local lactic acidosis. In this paper the results obtained by the administration of the lactate in 78 cases of hyperventilatory syndromes secondary to acute brain injuries, and the biochemistry of the cerebrospinal fluid and blood, are reported.

Concentrations of plasma and cerebrospinal fluid-free amino acids in hypercapnic coma and acute respiratory failure.

A comparison between the concentrations of free amino acids in the plasma and cerebrospinal fluid (CSF) in cases of hypercapnic coma and acute respiratory failure has been made. Hypotheses are formulated to interpret the observed changes in the cerebral metabolism of amino acids in these pathological conditions.

Büschke-Lowenstein tumour in pregnancy.

During pregnancy a localised human papillomavirus (HPV) lesion may, in rare cases, develop into a Büschke-Lowenstein tumour. The choice of treatment is crucial as standard systemic treatment is teratogenic. We performed laser CO2 microsurgery because it has a low incidence of complications.

The management of nonpigmented gallstones in children.

BACKGROUND/PURPOSE: An increasing number of children are diagnosed with gallstones today. The best management of nonpigmented gallstones in children without hematologic disorders is not known. METHODS: The authors prospectively studied 74 children with cholelithiasis diagnosed with ultrasonography. Clinical presentation, natural history, complications, and indications for cholecystectomy were examined. The follow-up (mean, 21 months) consisted of routine clinic visits, chart reviews, and telephone questionnaires with the children or their parents. RESULTS: Of the 74 children, 33 required cholecystectomies, and 41 were followed. The average age was similar in the 2 groups (11.7 v 11.0 years). Children with risk factors for cholelithiasis required earlier surgical treatment (P < .001). In the operative group, 8 presented acutely and 25 electively. There were 2 complications, a wound infection and a retained common duct stone. In the group that underwent follow-up, 34 of 41 children remained asymptomatic or had symptoms improve with dietary manipulation. No complications developed during the follow-up period. CONCLUSIONS: Children with gallstones and typical symptoms of right upper quadrant or epigastric pain with food intolerance should undergo cholecystectomy. Eighty-two percent of children with cholelithiasis and atypical symptoms had improvement with dietary manipulation. Pediatric patients with gallstones that are asymptomatic or associated with atypical symptoms can be safely followed without complications.

Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4.

OBJECTIVE: To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. METHODS: Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. RESULTS: Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. CONCLUSIONS: This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.