Validation of the fatigue severity scale in Croatian population of patients with multiple sclerosis disease: Factor structure, internal consistency, and correlates.

BACKGROUND: Fatigue is a common symptom in people with multiple sclerosis (MS) and is evaluated and monitored with self-report questionnaires. The objective of this study was to determine the psychometric properties of the Croatian version of the Fatigue Severity Scale (FSS) in people with MS. MATERIAL AND METHODS: This is a retrospective cohort study conducted as an online survey from December 16, 2020, until January 13, 2021. A total of 179 people with MS and 999 control subjects completed FSS and self-administered questionnaires capturing information of demographic, education level, disease-related variables (duration of the disease, MS type, the expanded disability status scale (EDSS), and Multiple Sclerosis Impact Scale-29 (MSIS-29). Psychometric properties were examined by estimating the validity, reliability, and factor structure of the FSS scale in people with MS. RESULTS: The Croatian version of the FSS had excellent internal consistency (Cronbach's α value 0.93). Factor analysis demonstrated a unidimensional structure. The concurrent validity of the FSS appeared to be satisfactory due to the significant differences between people with MS and control subjects (p < .05). The correlations between FSS and MSIS-29 physical (r = 0.60) and psychological (r = 0.50) subscale results confirmed the convergent validity of the FSS scale. Results also indicated that the best cut-off score is between 4 and 5 with a relatively high sensitivity and specificity. CONCLUSIONS: The Croatian version of FSS was shown to have excellent psychometric properties in people with MS and can be used in the research and clinical settings evaluating fatigue in people with MS in Croatia.

DEPRESSION AND FATIGUE ARE DUE TO OBSTRUCTIVE SLEEP APNEA IN MULTIPLE SCLEROSIS.

To our knowledge, there is no study investigating whether fatigue and depression as the most commonly reported symptoms in multiple sclerosis (MS) and obstructive sleep apnea (OSA) patients have arisen from primary mechanisms of MS or from secondary associated conditions such as OSA in MS patients. The aim of our survey study was to determine whether depression and fatigue in MS patients were associated with clinical features of OSA or with MS. We conducted a self-administered survey using four validated questionnaires (STOP-BANG, Epworth Sleepiness Scale, Fatigue Severity Scale and The Center for Epidemiologic Studies Depression Scale-Revised) in 28 consecutive outpatients with proven MS. The prevalence of MS patients at an increased risk of OSA was 29% and age was positively correlated with this risk (p=0.019). None of the clinical features of MS patients (subtype, disability status, disease duration, modifying therapy, other medication) was correlated with depression and fatigue. On the contrary, excessive daytime sleepiness as a hallmark of OSA was significantly and positively associated with the level of depressive symptoms (p=0.004) and level of fatigue (p=0.015). Also, depression was significantly and positively correlated with the increased risk of OSA (p=0.015) and age of MS patients (p=0.016). Finally, a significant positive correlation was found between fatigue severity and level of depressive symptoms (p=0.003). OSA is a common disorder in MS patients. The clinical features and risk factors for OSA in MS patients are associated with the two most commonly reported symptoms of depression and fatigue, thus supporting the hypothesis that both symptoms are due to a secondary condition in MS.

Obstructive Sleep Apnea Syndrome: A Preliminary Navigated Transcranial Magnetic Stimulation Study.

PURPOSE: An increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS. SUBJECTS AND METHODS: After acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18-28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed. RESULTS: The study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (ρ=-0.47) with MEP amplitude percentage deviation in OSAS patients. CONCLUSION: The nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.

Using Cutaneous Receptor Vibration to Uncover the Effect of Transcranial Magnetic Stimulation (TMS) on Motor Cortical Excitability.

BACKGROUND Little is known about how vibrational stimuli applied to hand digits affect motor cortical excitability. The present transcranial magnetic stimulation (TMS) study investigated motor evoked potentials (MEPs) in the upper extremity muscle following high-frequency vibratory digit stimulation. MATERIAL AND METHODS High-frequency vibration was applied to the upper extremity digit II utilizing a miniature electromagnetic solenoid-type stimulator-tactor in 11 healthy study participants. The conditioning stimulation (C) preceded the test magnetic stimulation (T) by inter-stimulus intervals (ISIs) of 5-500 ms in 2 experimental sessions. The TMS was applied over the primary motor cortex for the hand abductor pollicis-brevis (APB) muscle. RESULTS Dunnett's multiple comparisons test indicated significant suppression of MEP amplitudes at ISIs of 200 ms (P=0.001), 300 ms (P=0.023), and 400 ms (P=0.029) compared to control. CONCLUSIONS MEP amplitude suppression was observed in the APB muscle at ISIs of 200-400 ms, applying afferent signaling that originates in skin receptors following the vibratory stimuli. The study provides novel insight on the time course and MEP modulation following cutaneous receptor vibration of the hand digit. The results of the study may have implications in neurology in the neurorehabilitation of patients with increased amplitude of MEPs.

Diagnosis and Management of Acquired von Willebrand Disease in Heart Disease: A Review of the Literature.

The incidence of acquired von Willebrand syndrome (AvWS) in patients with heart disease is commonly perceived as rare. However, its occurrence is underestimated and underdiagnosed, potentially leading to inadequate treatment resulting in increased morbidity and mortality.In patients with cardiac disease, AvWS frequently occurs in patients with structural heart disease and in those undergoing mechanical circulatory support (MCS).The clinical manifestation of an AvWS is usually characterized by apparent or occult gastrointestinal (GI) or mucocutaneous hemorrhage frequently accompanied by signs of anemia and/or increased bleeding during surgical procedures. The primary change is loss of high-molecular weight von Willebrand factor multimers (HMWM). Whereas the loss of HMWM in patients with structural heart disease is caused by increased HMWM cleavage by von Willebrand factor (vWF)-cleaving protease, ADAMTS13, AvWS in MCS patients is predominantly a result of a high shear stress coupled with mechanical destruction of vWF itself.This manuscript provides a comprehensive review of the evidence regarding both diagnosis and contemporary management of AVWS in patients with heart disease.

MIPO of proximal humerus fractures through an anterolateral acromial approach. Is the axillary nerve at risk?

PURPOSE: It is known that shoulder surgery may cause iatrogenic injury to the axillary nerve as a serious complication, but there is little evidence to indicate whether the axillary nerve is at risk of injury during an anterolateral acromial approach for minimally-invasive plate osteosynthesis (MIPO) of proximal humerus fractures. We hypothesised that this surgical method is safe for the axillary nerve and would preserve it from iatrogenic injury. MATERIALS AND METHODS: We conducted a prospective follow-up cohort study on 49 consecutive patients with proximal humerus fractures who were managed with MIPO through an anterolateral approach. All patients underwent standardised electroneurographic testing, with assessment of amplitudes of evoked compound muscle action potentials (CMAP) and distal motor latencies (DML) of the axillary nerves, pre- and post-operatively. Six weeks after injury, all patients underwent needle electromyographic (EMG) testing of anterior, middle, posterior deltoid, teres minor and paraspinal muscles for detecting abnormal muscle activity as a sign of acute denervation. After six months of physical rehabilitation, patients with axillary nerve injury underwent control electroneurographic testing to check the recovery of neurographic features (CMAP, DML). All nerve measurements were compared to reference values, and between right and left side. RESULTS: Five patients had a mild-to-moderate traumatic axillary nerve injury before surgery. There were no significant differences between amplitudes of CMAP (p = 0.575) and DML (p = 0.857) pre- and post-surgical procedure. CONCLUSIONS: These results confirmed safety of this surgical method in the preservation of axillary nerve from iatrogenic injury, but the course of the axillary nerve must be kept in mind.

CSF tap test - Obsolete or appropriate test for predicting shunt responsiveness? A systemic review.

OBJECTIVES: There is no accurate test for diagnosing normal pressure hydrocephalus or for screening for patients who will benefit from shunt surgery. Additional tests, such as cerebrospinal fluid tap test (CSF-TT), are often used in practice to provide further predictive value in detecting suitable patients for shunting. We performed a systematic review of the literature to evaluate the CSF-TT's effect on the outcome of main symptoms and on validity parameters in screening patients suitable for shunting. METHODS: In February 2015 we searched electronic databases from their inception to the current date, using the following key words: normal pressure hydrocephalus, idiopathic normotensive hydrocephalus, shunt operation, CSF tap test, predictive value, validity. The search retrieved 8 articles explicitly addressing the topic. RESULTS: There was a very high positive predictive value of CSF-TT: 92% (range from 73% to 100%) but a low negative predictive value: 37% (18%-50%). Also, the CSF-TT has high specificity: 75% (33%-100%) but average sensitivity: 58% (26%-87%). The overall accuracy of the test was 62% (45%-83%). CONCLUSIONS: This systematic review did not provide unambiguous validity of the CSF-TT in the screening of patients for shunting. The validity of the CSF-TT is good for patient inclusion for shunting due to the fact that the positive response to the test is very reliable. Unfortunately, the negative response to the test does not reliably make these patients ineligible for shunting. Further studies are needed to improve and standardize the methodology in order to optimize the detection power of the test.

Reduced evoked motor and sensory potential amplitudes in obstructive sleep apnea patients.

It is unknown to what extent chronic intermittent hypoxaemia in obstructive sleep apnea causes damage to the motor and sensory peripheral nerves. It was hypothesized that patients with obstructive sleep apnea would have bilaterally significantly impaired amplitudes of both motor and sensory peripheral nerve-evoked potentials of both lower and upper limbs. An observational study was conducted on 43 patients with obstructive sleep apnea confirmed by the whole-night polysomnography, and 40 controls to assess the relationship between obstructive sleep apnea and peripheral neuropathy. All obstructive sleep apnea subjects underwent standardized electroneurographic testing, with full assessment of amplitudes of evoked compound muscle action potentials, sensory neural action potentials, motor and sensory nerve conduction velocities, and distal motor and sensory latencies of the median, ulnar, peroneal and sural nerves, bilaterally. All nerve measurements were compared with reference values, as well as between the untreated patients with obstructive sleep apnea and control subjects. Averaged compound muscle action potential and sensory nerve action potential amplitudes were significantly reduced in the nerves of both upper and lower limbs in patients with obstructive sleep apnea compared with controls (P < 0.001). These results confirmed that patients with obstructive sleep apnea had significantly lower amplitudes of evoked action potentials of both motor and sensory peripheral nerves. Clinical/subclinical axonal damage exists in patients with obstructive sleep apnea to a greater extent than previously thought.

MULTIPLE INTRACRANIAL SCHWANNOMAS: CASE REPORT.

Schwannomas are benign encapsulated tumors arising from the sheaths of peripheral nerves. They present as slowly enlarging solitary lumps, which may cause neurological defects. Multiple schwannomas in non-neurofi bromatosis type 2 patients are extremely rare. We report a case of a 60-year-old female patient, without any family history of neurofibromatosis or schwannomatosis, presented with trigeminal neuralgia and progressive facial nerve palsy. Magnetic resonance imaging revealed the presence of acoustic schwannoma involving facial nerve and trigeminal schwannoma of the cisternal part of the nerve involving gasserian ganglion (Meckel's cave). After gamma knife radiosurgery, trigeminal neuralgia was relieved completely with improvement of facial nerve palsy.

Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery.

In patients undergoing coronary artery surgery, improvements in clinical outcomes currently rely on continued refinements of the surgical technique and modulation of adjuvant pharmacotherapy. Despite medical and technological advances, negligible rate of bleeding and ischemic events still persist necessitating further improvements in patient management. Platelet function testing (PFT) might play an important role in meticulous balancing between the risk of bleeding and thrombotic events. A suitable balance can be achieved by implementing a personalized, PFT based approach in antiplatelet therapy (APT) administration/discontinuation management. Despite emerging evidence on the widespread variability in platelet inhibitory response to APT, numerous PFT devices and heterogeneity in reporting study results hamper pooling of the evidence which in turn results with a lack of consensus in "on treatment" platelet reactivity associated with ischemic and bleeding events in perioperative phase. The literature on multiple electrode aggregometry (Multiplate(®); Roche Diagnostics, Mannheim, Germany) in coronary artery disease patients was reviewed systematically. Based on the evidence evaluating the relationship between "drug specific" PFT and bleeding or adverse ischemic events, we sought to define therapeutic window for the most commonly administered antiplatelet drugs such as aspirin (ASPI test) and adenosine-diphosphate receptor blockers (ADP test). Preoperatively, APT administration was primarily focused to avoid bleeding complications. ASPI test value of 20 AUC and ADP test value of <73 AUC were set as cut-off values that delineate bleeding tendency. Postoperatively, "therapeutic window" was set to avoid both bleeding and adverse ischemic events. Therapeutic ranges were as follows: 20 AUC < ASPItest ≤ 30 AUC and 19AUC < ADP ≤ 46AUC, respectively. This is the first attempt to define PFT based "therapeutic window" according to, perioperative APT administration/discontinuation management would be targeted. It seems that the "one-size-fits-all" concept of perioperative APT administration management is outdated and further development of PFT based, personalized APT administration/discontinuation management is desirable. This concept therefore presents a possible step forward in patient care and provides a platform for further interventional trials whereby the impact of its application on clinical outcomes would be validated.

The Event-related Potential P300 in Patients with Migraine.

OBJECTIVE: Recording of event-related potentials by using oddball paradigm of auditory P300 has yielded conflicting results in migraine. The aim of this study was to demonstrate that migraine patients have reduced P300 amplitude and prolonged P300 latency, suggesting alterations of the cognitive-evaluative component. METHODS: We recruited 29 migraine patients (24 females; median age 40 years) and 29 healthy age- and gender-matched participants. Participants were subjected to the same testing procedures of auditory P300 by discrimination the target auditory stimulus from the frequent stimulus, and analyzing P300 target/frequent stimulus amplitudes, and P300 target/frequent stimulus latencies. RESULTS: Patients with migraine don't have prolonged P300 target stimulus latency, but have a longer P300 frequent stimulus latency for 17.5ms. Out of 29 participants with migraine 8 had pathological P300 target stimulus amplitude, and 19 had pathological P300 frequent stimulus amplitude. CONCLUSION: People with migraine have altered the P300 which indicates the presence of cognitive dysfunction in these patients and importance of early diagnosis and intervention to preventing any deterioration in cognitive functions.

How severe is depression in low back pain patients?

The aim of the present study was to determine the prevalence of depression among low back pain (LBP) patients and to investigate the sociodemographic characteristics of pa- tients with LBP and relationship between depression and pain intensity in LBP patients. The study was conducted on 99 patients treated at Clinical Department of Neurology, Split University Hospital Center. There were 36 (36%) men and 63 (64%) women. Some degree of depression was present in 73 (74%) study patients, including all patients with severe LBP. In the group of patients with severe LBP, the rate of moderate, severe and very severe depression was 1.36-fold that recorded in the gro- up of patients with moderate LBP and 2.58-fold that found in the group of patients with mild LBP (χ2 = 16.2; p = 0.003). The most common symptoms were general physical symptoms 70 (71%), psychic anxiety 69 (70%) and depressed mood 66 (67%). It is concluded that depression was more severe in LBP patients with severe disease compared to patients with mild or moderate LBP.

Sensomotor axonal peripheral neuropathy as a first complication of polycythemia rubra vera: A report of 3 cases.

PATIENT: Female, 64 FINAL DIAGNOSIS: Polycythemia rubra vera Symptoms: Burning pain • cramps • hypesthesia • itching • paresthesia MEDICATION: - Clinical Procedure: - Specialty: Neurology. OBJECTIVE: Unusual clinical course. BACKGROUND: The association between polycythemia vera and peripheral neuropathy has been described previously but only as a late complication and only with sensory axonal polyneuropathy. We presume the cause of polyneuropathy was hypoxia due to higher blood viscosity and dysfunction of platelet aggregation. CASES REPORT: We report the cases of 3 female patients with symptoms and signs of slowly progressive sensorimotor axonal polyneuropathy confirmed with clinical and neurographic examination as first complication of polycythemia vera, which progressed to a major complication. Axonal damage was irreversible despite venipuncture. CONCLUSIONS: Polycythemia vera is rarely manifested with symptoms of sensomotor polyneuropathy as the first signs of the disease, and should therefore be recognized by physicians to prevent further axonal damage and major complications of disease by venipuncture or cytostatic therapy.

Platelet adhesion onto immobilized fibrinogen under arterial and venous in-vitro flow conditions does not significantly differ between men and women.

BACKGROUND: Gender-related differences in incidence of arterial thrombosis have been a focus of interest for years. The platelet integrin alphaIIbbeta3 is primarily responsible for the interaction between platelets and fibrinogen and consecutive thrombus growth. In this study, we evaluated platelet adhesion onto immobilized fibrinogen under venous and arterial flow conditions in men and women. METHODS: Platelets in whole anticoagulated blood were labelled with the fluorescence dye Mepacrine and perfused through the rectangular flow chamber over glass cover slips coated with fibrinogen (shear rates of 50 s-1, 500 s-1 and 1500 s-1). A fluorescence laser-scan microscope was used for visualisation and quantification of platelet adhesion at 15 seconds, 1 and 5 minutes after the start of perfusion. RESULTS: During perfusion, the platelet adhesion linearly increased in regard to exposition time and shear rate. After five minutes of perfusion the platelet adhesion onto immobilized fibrinogen showed no significant gender related difference, neither at 50 s-1 nor at 500 s-1 and 1500 s-1 (p > 0.05), respectively. No significant difference in platelet adhesion onto immobilized fibrinogen, in regard to the menopausal status, was either observed (p > 0.05). CONCLUSION: In our in vitro experimental system, hormonal differences between men and women did not influence platelet adhesion onto immobilized fibrinogen, neither under venous nor under arterial rheological conditions.

HPA-1 polymorphism of alphaIIbbeta3 modulates platelet adhesion onto immobilized fibrinogen in an in-vitro flow system.

BACKGROUND: Platelet adhesion and subsequent thrombus formation on a subendothelial matrix at the site of vascular damage play a crucial role in the arrest of posttraumatic bleeding but also in different pathological thrombotic events, such as acute coronary syndrome and stroke. Recently published studies have clearly demonstrated that platelet integri alphaIIbbeta3 is intimately involved in the occlusive thrombus formation at the site of endothelial damage. Therefore, any genetic variation in the expression of this receptor may lead to an excessive bleeding or excessive thrombus formation. In this study, we evaluated the influence of HPA-1 polymorphism of integrin alphaIIbbeta3 on platelet adhesion onto immobilized fibrinogen using an in vitro system simulating blood flow. METHODS: Platelets in anticoagulated whole blood [49 healthy previously genotyped blood donors) were labelled with fluorescence dye and perfused through a rectangular flow chamber (shear rates of 50 s(-1), 500 s(-1) and 1500 s(-1)). A fluorescence laser-scan microscope was used for visualisation and quantification of platelet adhesion at 15 sec, 1 and 5 minutes after start of perfusion. RESULTS: During perfusion, the platelet adhesion linearly increased with regard to exposition time and shear rate. Perfusion of blood preincubated with Abciximab over fibrinogen-coated cover-slips showed reduced platelet adherence (absolute fluorescence: 168 +/- 35 U vs. 53000 +/- 19000 at control experiments, p < 0.05), as well as by perfusion over BSA-coated glass coverslips. Platelet with HPA-1a/1a genotype exhibited initial better adhesion but they also exhibited higher detachment under arterial flow conditions compared to the HPA-1b/1b platelets. Analysis of stable adhesion rate indicate that the platelets carrying the HPA-1b/1b genotype have a higher reactivity threshold for initial interaction with fibrinogen but under the higher shear rate (in regard to time of perfusion) also realize more stable bonds with fibrinogen than platelets with the HPA-1a/1a genotype. CONCLUSION: Our data support the contention that genetically determined variants of platelet integrins alphaIIbbeta3 could play a role in arterial thrombogenesis and thus confirm the hypothesis derived from epidemiological studies.