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Article: Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.

De Marchi, Fabiola / Munitic, Ivana / Vidatic, Lea / Papić, Eliša / Rački, Valentino / Nimac, Jerneja / Jurak, Igor / Novotni, Gabriela / Rogelj, Boris / Vuletic, Vladimira / Liscic, Rajka M / Cannon, Jason R / Buratti, Emanuele / Mazzini, Letizia / Hecimovic, Silva

Biomedicines

2023 Volume 11, Issue 10

Abstract: Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in ... ...

Abstract	Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors. In this review, we compare these neurodegenerative diseases from a clinical point of view and highlight common pathways and mechanisms of protein aggregation, neurodegeneration, and/or neuroinflammation that could potentially lead to shared treatment strategies for overlapping immune dysfunctions in these diseases. These approaches include but are not limited to immunisation, complement cascade blockade, microbiome regulation, inhibition of signal transduction, Treg boosting, and stem cell transplantation.
Language	English
Publishing date	2023-10-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11102793
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Article: Functional organisation of the facial motor system in man.

Liscić, R M / Zidar, J

Collegium antropologicum

1998 Volume 22, Issue 2, Page(s) 545–550

Abstract: To investigate human corticobulbar projections, electromyographic responses from orbicularis oculi and orbicularis oris muscles were recorded in 11 healthy subjects after transcranial magnetic stimulation. Selective activation of lower facial ... ...

Abstract	To investigate human corticobulbar projections, electromyographic responses from orbicularis oculi and orbicularis oris muscles were recorded in 11 healthy subjects after transcranial magnetic stimulation. Selective activation of lower facial motoneurones of one hemisphere was reached with the round coil 4 cm lateral to the vertex on a line to the external auditory meatus with stimulus intensities from 45 to 55% (100% = 1.5 T). The mean latency of the OR muscle was 11.5 +/- 1.77 ms contralaterally. Ipsilateral cortical responses were observed in 5 subjects (45%) at a mean latency of 13.88 +/- 2.17 ms. Corticobulbar innervation may have affected bilateral responses in the lower facial muscles as those persisted even after lidocaine blockade of both supraorbital nerves. The functional importance of ipsilateral projections to the lower facial muscles in man is lower than that of the contralateral projections, as evidenced by the fact that they cannot be observed in all subjects or in all motor units. The influence of the trigeminal sensory afferents was excluded from the study after blockade of both supraorbital nerves.
MeSH term(s)	Adult ; Electric Stimulation ; Electromyography ; Facial Muscles/innervation ; Female ; Humans ; Magnetics ; Male ; Motor Cortex/physiology ; Nerve Block ; Neural Pathways ; Skin/innervation
Language	English
Publishing date	1998-12
Publishing country	Croatia
Document type	Journal Article
ZDB-ID	233430-6
ISSN	0350-6134 ; 0353-3735
ISSN	0350-6134 ; 0353-3735
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Article: Intramedullar stimulation of the facial and hypoglossal nerves: estimation of the stimulated site.

Liscić, R M / Morota, N / Deletis, V

Croatian medical journal

2000 Volume 41, Issue 4, Page(s) 384–388

Abstract: Aim: To determine the stimulation site of both facial and hypoglossal nerves after transcranial magnetic stimulation.: Methods: After surgical exposure of the brainstem in 22 patients with intrinsic pontine (n=9) or medullary (n=13) tumors, the ... ...

Abstract	Aim: To determine the stimulation site of both facial and hypoglossal nerves after transcranial magnetic stimulation. Methods: After surgical exposure of the brainstem in 22 patients with intrinsic pontine (n=9) or medullary (n=13) tumors, the facial colliculus and the hypoglossal triangle were electrically stimulated. The EMG responses were recorded with flexible wire electrodes from the orbicularis oculi/orbicularis oris muscles, and genioglossal muscles. Patients had no preoperative deficit of the nerves. Results: The EMG mean latencies of the unaffected facial nerve were 5.2+/-0.6 ms for the orbicularis oculi, and 5.2+/-0.5 ms for the orbicularis oris muscle. After the stimulation of 18 possibly affected facial nerves, the EMG mean latencies were 5.3+/-0.3 ms for the orbicularis oculi (p=0.539, unpaired Student's t-test), and 5.4+/-0.2 ms for the orbicularis oris (p=0.122). The EMG mean latency of the unaffected hypoglossal nerve was 4.1+/-0.6 ms for the genioglossal muscle. After the stimulation of 26 possibly affected hypoglossal nerves, the EMG mean latency for the genioglossal muscle was 5.3+/-0.3 ms. There was a significant difference (p<0.001) in latency for genioglossal EMG responses between the patients with pontine and those with medullary tumors. Conclusion: Shorter EMG mean latencies of unaffected facial nerves obtained after direct stimulation of the facial colliculi confirm that magnetic stimulation is most likely to occur closer to the nerve's exit from the brainstem than to its entrance into the internal auditory meatus. The hypoglossal nerve seems to have the site of excitation at the axon hillock of the hypoglossal motor neurons.
MeSH term(s)	Adolescent ; Adult ; Brain Stem Neoplasms/surgery ; Child ; Child, Preschool ; Electric Stimulation ; Electromyography ; Evoked Potentials ; Facial Nerve/physiology ; Female ; Humans ; Hypoglossal Nerve/physiology ; Magnetics ; Male ; Middle Aged ; Monitoring, Intraoperative ; Muscle, Skeletal/innervation ; Reaction Time
Language	English
Publishing date	2000-12
Publishing country	Croatia
Document type	Journal Article
ZDB-ID	1157623-6
ISSN	1332-8166 ; 0353-9504
ISSN (online)	1332-8166
ISSN	0353-9504
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Article ; Online: Differentiation of progressive supranuclear palsy: clinical, imaging and laboratory tools.

Liscic, R M / Srulijes, K / Gröger, A / Maetzler, W / Berg, D

Acta neurologica Scandinavica

2013 Volume 127, Issue 5, Page(s) 362–370

Abstract: Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian syndrome comprising two main clinical subtypes: Richardson's syndrome (RS), characterized by prominent postural instability, supranuclear vertical gaze palsy and frontal ... ...

Abstract	Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian syndrome comprising two main clinical subtypes: Richardson's syndrome (RS), characterized by prominent postural instability, supranuclear vertical gaze palsy and frontal dysfunction; and PSP-parkinsonism (PSP-P) which is characterized by an asymmetric onset, tremor and moderate initial therapeutic response to levodopa. The early clinical features of PSP-P are often difficult to discern from idiopathic Parkinson's disease (PD), and other atypical parkinsonian disorders, including multiple system atrophy (MSA) and corticobasal syndrome (CBS). In addition, rare PSP subtypes may be overlooked or misdiagnosed if there are atypical features present. The differentiation between atypical parkinsonian disorders and PD is important because the prognoses are different, and there are different responses to therapy. Structural and functional imaging, although currently of limited diagnostic value for individual use in early disease, may contribute valuable information in the differential diagnosis of PSP. A growing body of evidence shows the importance of CSF biomarkers in distinguishing between atypical parkinsonian disorders particularly early in their course when disease-modifying therapies are becoming available. However, specific diagnostic CSF biomarkers have yet to be identified. In the absence of reliable disease-specific markers, we provide an update of the recent literature on the assessment of clinical symptoms, pathology, neuroimaging and biofluid markers that might help to distinguish between these overlapping conditions early in the course of the disease.
MeSH term(s)	Age of Onset ; Biomarkers ; Brain/pathology ; Gait Disorders, Neurologic/diagnosis ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Multiple System Atrophy/diagnosis ; Neuroimaging/methods ; Parkinsonian Disorders/classification ; Parkinsonian Disorders/diagnosis ; Positron-Emission Tomography ; Prognosis ; Supranuclear Palsy, Progressive/classification ; Supranuclear Palsy, Progressive/diagnosis ; Supranuclear Palsy, Progressive/metabolism ; Supranuclear Palsy, Progressive/pathology ; Symptom Assessment ; Ultrasonography, Doppler, Transcranial ; alpha-Synuclein/cerebrospinal fluid ; tau Proteins/analysis
Chemical Substances	Biomarkers ; MAPT protein, human ; alpha-Synuclein ; tau Proteins
Language	English
Publishing date	2013-05
Publishing country	Denmark
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	90-5
ISSN	1600-0404 ; 0001-6314
ISSN (online)	1600-0404
ISSN	0001-6314
DOI	10.1111/ane.12067
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Article: Epidemiological characteristics of sarcoidosis patients hospitalized in the Uuniversity Hospital for Lung Diseases "Jordanovac" (Zagreb, Croatia) in the 1997-2002 period.

Alilović, Marija / Peros-Golubicić, Tatjana / Tekavec-Trkanjec, Jasna / Smojver-Jezek, Silvana / Liscić, Rajka

Collegium antropologicum

2006 Volume 30, Issue 3, Page(s) 513–517

Abstract: The aim of our study was to explore the characteristics of hospitalized patients with sarcoidosis concerning age, gender, clinical forms and staging, seasonality, geographical distribution, smoking habit and profession, familial clustering and mortality. ...

Abstract	The aim of our study was to explore the characteristics of hospitalized patients with sarcoidosis concerning age, gender, clinical forms and staging, seasonality, geographical distribution, smoking habit and profession, familial clustering and mortality. We included 476 biopsy-proven sarcoidosis patients who were diagnosed at the University Hospital for Lung Diseases "Jordanovac" in the period from 1997-2002. Most of the patients (44%) were in the group of age between 20 and 40 years. The ratio of women to men was 1.4:1. The onset of the disease usually appeared in spring and summer, especially in the patients presenting with erythema nodosum, with majority of patients hospitalized in the period from May to August (51%). More patients came from urban, than from rural areas (1.5:1), and they were mostly nonsmokers (3.3:1). In 2% of sarcoidosis patients we found familial clustering. Although these data are biased regarding the selection of patients they give new insights into characteristics of sarcoidosis patients in Croatia.
MeSH term(s)	Adult ; Age Distribution ; Aged ; Croatia/epidemiology ; Erythema Nodosum/epidemiology ; Female ; Hospitalization/statistics & numerical data ; Hospitals, University ; Humans ; Life Style ; Male ; Middle Aged ; Registries ; Sarcoidosis/epidemiology ; Sarcoidosis/mortality ; Sarcoidosis/physiopathology ; Seasons ; Sex Distribution ; Urban Population
Language	English
Publishing date	2006-09
Publishing country	Croatia
Document type	Journal Article
ZDB-ID	233430-6
ISSN	0350-6134 ; 0353-3735
ISSN	0350-6134 ; 0353-3735
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Article: A custom designed system to measure corticospinal tract jitter.

Mihelin, M / Liscic, R M

Electroencephalography and clinical neurophysiology

1998 Volume 109, Issue 2, Page(s) 194–197

Abstract: Typical latency of an individual limb muscle response to magnetic or electric stimulation of the human cortex is in the range of 10-50 ms. For the latency variability, i.e., jitter studies, a resolution of at least 20 micros is needed. Commercially ... ...

Abstract	Typical latency of an individual limb muscle response to magnetic or electric stimulation of the human cortex is in the range of 10-50 ms. For the latency variability, i.e., jitter studies, a resolution of at least 20 micros is needed. Commercially available EMG equipment needs custom-designed upgrading to allow for such studies. Two solutions were designed: (i) a hardware unit allowing an adjustable delay of data acquisition after the delivered stimuli; and (ii) diverting of the amplified biological signal and the EMG equipment trigger to an external computer equipped with an analogue-to-digital conversion (ADC) module. Custom-designed software made fast ADC possible during the whole period of data acquisition. Both concepts were applied to a Vickers Medical Mystro electromyograph, and have been successfully used in the Ljubljana (Slovenia) Institute of Clinical Neurophysiology for the last 2 years.
MeSH term(s)	Brain Mapping/instrumentation ; Electric Stimulation ; Electromagnetic Fields ; Electromyography/instrumentation ; Humans ; Microcomputers ; Motor Cortex/physiology ; Muscle, Skeletal/innervation ; Muscle, Skeletal/physiology ; Pyramidal Tracts/physiology
Language	English
Publishing date	1998-04
Publishing country	Ireland
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial
ZDB-ID	216210-6
ISSN	0013-4694 ; 0168-5597 ; 0921-884X ; 0924-980X
ISSN	0013-4694 ; 0168-5597 ; 0921-884X ; 0924-980X
DOI	10.1016/s0924-980x(97)00079-9
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Article: Event-related potentials in medical workers with long-term exposure to xylene.

Liscić, R M / Skender, L / Jakić-Razumović, J / Simić, D / Milković-Kraus, S

Collegium antropologicum

2001 Volume 25, Issue 1, Page(s) 357–362

Abstract: ... to xylene was confirmed through determination of m-methylhippuric acid, a reliable biological indicator ... of xylene exposure, in pre- and post-shift urine. A dose-effect relationship between log m-methylhippuric ...

Abstract	The effects of chronic exposure to xylene on cognitive ability were studied in a group of 35 medical workers occupationally exposed to low-level concentrations of xylene for at least five years by using event-related potentials (ERPs), and compared with a control group of 21 subjects. The exposure to xylene was confirmed through determination of m-methylhippuric acid, a reliable biological indicator of xylene exposure, in pre- and post-shift urine. A dose-effect relationship between log m-methylhippuric acid and ERP log latency (p = 0.032), and the ERP amplitude (p = 0.047) was statistically significant. The group of medical workers showed significantly longer ERP log latency (p < 0.001) than did the control group with respect to factors of exposure to smoking, education and age as covariates. For the ERP amplitude the difference was found not to be significant (p = 0.263), probably due to high between subject variability. The cognitive impairment may occur in workers chronically exposed to xylene.
MeSH term(s)	Adult ; Cognition Disorders/chemically induced ; Dose-Response Relationship, Drug ; Evoked Potentials ; Female ; Health Personnel ; Humans ; Inhalation Exposure ; Male ; Middle Aged ; Occupational Exposure ; Xylenes/adverse effects
Chemical Substances	Xylenes
Language	English
Publishing date	2001-06
Publishing country	Croatia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	233430-6
ISSN	0350-6134 ; 0353-3735
ISSN	0350-6134 ; 0353-3735
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Article: Rano prepoznavanje Churg-Straussova sindroma.

Bekić, Anto / Peros-Golubicić, Tatjana / Tekavec-Trkanjec, Jasna / Alilović, Marija / Gorecan, Marijan / Liscić, Rajka

Lijecnicki vjesnik

2002 Volume 124, Issue 6-7, Page(s) 195–198

Abstract: We present a patient with Churg-Strauss syndrome which appeared with asthma, chronic sinuitis, peripheral and tissue oeosinophilia, migratory pulmonary infiltrates and polyneuropathy but without histologically proven granuloma or vasculitis. The patient ... ...

Title translation	Early recognition of Churg-Strauss syndrome.
Abstract	We present a patient with Churg-Strauss syndrome which appeared with asthma, chronic sinuitis, peripheral and tissue oeosinophilia, migratory pulmonary infiltrates and polyneuropathy but without histologically proven granuloma or vasculitis. The patient successfully recovered under corticosteroid therapy. The aim of this presentation is early recognition of Churg-Strauss syndrome in order to timely diagnose and treat these patients.
MeSH term(s)	Churg-Strauss Syndrome/diagnosis ; Churg-Strauss Syndrome/drug therapy ; Female ; Humans ; Middle Aged
Language	Croatian
Publishing date	2002-06
Publishing country	Croatia
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	128938-x
ISSN	1849-2177 ; 0024-3477 ; 1330-4917
ISSN (online)	1849-2177
ISSN	0024-3477 ; 1330-4917
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Article ; Online: ALS and FTLD: two faces of TDP-43 proteinopathy.

Liscic, R M / Grinberg, L T / Zidar, J / Gitcho, M A / Cairns, N J

European journal of neurology

2008 Volume 15, Issue 8, Page(s) 772–780

Abstract: Major discoveries have been made in the recent past in the genetics, biochemistry and neuropathology of frontotemporal lobar degeneration (FTLD). TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the major ... ...

Abstract	Major discoveries have been made in the recent past in the genetics, biochemistry and neuropathology of frontotemporal lobar degeneration (FTLD). TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the major pathological protein of FTLD with ubiquitin-immunoreactive (ub-ir) inclusions (FTLD-U) with or without amyotrophic lateral sclerosis (ALS) and sporadic ALS. Recently, mutations in the TARDBP gene in familial and sporadic ALS have been reported which demonstrate that abnormal TDP-43 alone is sufficient to cause neurodegeneration. Several familial cases of FTLD-U, however, are now known to have mutations in the progranulin (GRN) gene, but granulin is not a component of the TDP-43- and ub-ir inclusions. Further, TDP-43 is found to be a component of the inclusions of an increasing number of neurodegenerative diseases. Other FTLD-U entities with TDP-43 proteinopathy include: FTLD-U with valosin-containing protein (VCP) gene mutation and FTLD with ALS linked to chromosome 9p. In contrast, chromosome 3-linked dementia, FTLD-U with chromatin modifying protein 2B (CHMP2B) mutation, has ub-ir, TDP-43-negative inclusions. In summary, recent discoveries have generated new insights into the pathogenesis of a spectrum of disorders called TDP-43 proteinopathies including: FTLD-U, FTLD-U with ALS, ALS, and a broadening spectrum of other disorders. It is anticipated that these discoveries and a revised nosology of FTLD will contribute toward an accurate diagnosis, and facilitate the development of new diagnostic tests and therapeutics.
MeSH term(s)	Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Dementia/genetics ; Dementia/metabolism ; Dementia/pathology ; Humans
Chemical Substances	DNA-Binding Proteins
Language	English
Publishing date	2008-08-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/j.1468-1331.2008.02195.x
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Article: Creutzfeldt-Jakob disease in a patient with a lyophilized dura mater graft.

Liscić, R M / Brinar, V / Miklić, P / Barsić, B / Himbele, J

Acta medica Croatica : casopis Hravatske akademije medicinskih znanosti

1999 Volume 53, Issue 2, Page(s) 93–96

Abstract: A 37-year-old patient with Creutzfeldt-Jakob disease (CJD) is presented, who had received a cadaveric dura matter graft 12 year before the onset of neurologic symptoms. Initial clinical presentation included cerebellar symptoms, with dementia and ... ...

Abstract	A 37-year-old patient with Creutzfeldt-Jakob disease (CJD) is presented, who had received a cadaveric dura matter graft 12 year before the onset of neurologic symptoms. Initial clinical presentation included cerebellar symptoms, with dementia and myoclonus developing in later stages of the disease. EEG showed diffuse slowing with sporadic triphasic periodic activity. CT was normal in the early stage but pronounced cerebral and cerebellar atrophy with widened sulci were seen on MRI in the late stage of the disease. The prion protein (PrP) gene was homozygous for valin at the polymorphic codon 129. Cerebrospinal fluid analysis for 14-3-3 protein was positive. We believe that this patient is the first Croatian to acquire CJD by dural implant. Based on this case and a review of 66 cases from the literature, it is manifest that the awareness of iatrogenic transmission of CJD and adoption of preventive measures are the only effective way to stop the spread of CJD among surgically treated patients.
MeSH term(s)	Adult ; Cadaver ; Creutzfeldt-Jakob Syndrome/diagnosis ; Creutzfeldt-Jakob Syndrome/etiology ; Dura Mater/transplantation ; Freeze Drying ; Humans ; Male ; Tissue Preservation ; Transplantation, Homologous/adverse effects
Language	English
Publishing date	1999
Publishing country	Croatia
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	1108025-5
ISSN	1330-0164 ; 0375-8338
ISSN	1330-0164 ; 0375-8338
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