Post-COVID-19 Syndrome in Neurology Patients: A Single Center Experience.

Our aim was to determine the frequency and characteristics of neurological post-COVID-19 syndrome and the diagnostic and therapeutic measures that were used for the treatment of these patients. Data were collected for 243 patients examined during the period of 11 May 2021 to 22 June 2022. The inclusion criteria were COVID-19 illness and neurological symptoms associated with COVID-19. The exclusion criteria were non-neurological symptoms, patients who did not suffer from COVID-19, and symptoms that occurred after vaccination against the SARS-CoV-2 virus. Data for 227 patients with neurological post-COVID-19 symptoms were analyzed. Most patients presented with multiple symptoms, most often headache, cognitive impairment, loss of smell, paresthesia, fatigue, dizziness, and insomnia. Patients were most often referred for consultative examinations, neuroradiological imaging, and EEG. The therapy was mostly symptomatic. Most patients had no change in their symptoms on follow-up visits (53.21%), while positive outcome was found in 44.95% of patients. This study found that neurological post-COVID-19 syndrome appears to be more common in women, and generally, the most common symptoms are headache and cognitive impairment. The gender distribution of symptoms was clearly visible and should be further investigated. There is a need for longitudinal follow-up studies to better understand the disease dynamic.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and interferon-ß treatment response in multiple sclerosis patients: a preliminary report.

We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-ß (IFN-ß) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-ß treated MS patients [162 responders (Rs) and 113 nonresponders (NRs)] were genotyped by PCR. The ACE I/D genotype distribution and allele frequencies did not differ between female Rs and NRs. However, male NRs tended to have a greater prevalence of the DD genotype (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91-7.60) and a significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95% confidence interval: 1.13-5.20) than male Rs. Multiple forward stepwise regression analysis indicated that the negative response to IFN-ß therapy was associated with the ACE-DD genotype in men (ß=0.371; multiple R change: 0.132; P=0.009) and a higher pretreatment relapse rate in both men (ß=-0.438; multiple R change: 0.135; P=0.015) and women (ß=-0.208; multiple R change: 0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted for ∼26.7% of the IFN-ß response variability among the men in the sample. Further studies of a larger number of MS patients from different populations are necessary to evaluate these preliminary findings.

A patient with myasthenia gravis and a large arachnoid cyst - report of a case.

Myasthenia gravis is a chronic autoimmune disease characterized by weakening of voluntary muscles during the day and a marked restitution of function during the night and after rest. The symptoms may worsen over days or weeks, sometimes even in a few hours, and are usually well controlled by appropriate therapy. Arachnoid cysts are congenital or acquired deformities of the arachnoid membrane and are usually too small to cause distinct clinical symptomatology. We describe a case of a 76-year-old myasthenia gravis patient with an arachnoid cyst. To the best of our knowledge this is the first reported case of these two comorbidities together.

MMP-2 -1575G/A polymorphism modifies the onset of optic neuritis as a first presenting symptom in MS?

Previous studies show altered activities of matrix metalloproteinase (MMP)-2 and MMP-9 in serum and cerebrospinal fluid of multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. Optic neuritis (ON) is a common symptom of both disorders. Here we investigated the impacts of MMP-2 -1575G/A and MMP-9 -1562 C/T gene polymorphisms on disease phenotype in 100 MS patients with ON as a first symptom and 376 MS patients with other initial symptomatology. The MMP-2 -1575G/A polymorphism led to a 5-year-earlier age of disease onset in MS patients with ON as a first symptom (p=0.009).

The role of TPA I/D and PAI-1 4G/5G polymorphisms in multiple sclerosis.

BACKGROUND: Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). METHODS: The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. RESULTS: TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63-0.99, P = 0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01-1.66, P = 0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06-1.82, P = 0.017). CONCLUSIONS: We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS.

Susac's syndrome during pregnancy - the first Croatian case.

Susac's syndrome (SS) is an infrequent neurological disorder characterized by the clinical triad of encephalopathy, branch retinal artery occlusion and hearing loss due to an autoimmune endotheliopathy associated with anti-endothelial cell antibodies. At the onset of the disease SS rarely appears with the complete clinical triad. The most important diagnostic procedures involved in the diagnosis of SS are brain MRI, audiometric testing and retinal fluorescein angiography. Presence of at least two components of the SS clinical triad accompanied by specific brain MRI findings is highly suggestive of SS. We report a case of a young pregnant woman with a history of encephalopathy, hearing loss and walking impairment. Brain MRI revealed a spectrum of findings previously described in patients with SS. We induced labor at 37 weeks' gestation to start with immunosuppressive treatment and avoid possible fetal toxicity. To the best of our knowledge this is the first report of SS in Croatia.

Intravenous thrombolysis for acute ischemic stroke--our experiences.

Intravenous (i.v.) thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the only available pharmacological therapy to improve the outcome of acute ischemic stroke. We compared 71 patients presenting with ischaemic stroke and given intravenous rt-PA (0.9 mg/kg total dose) within 3 h with 71 patients who present to the hospital more than 3 hours after stroke symptom onset. The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable and unfavourable (score 2-6). Outcome measures were symptomatic intracerebral haemorrhage within 36 h (haemorrhage associated with National Institutes of Health Stroke Scale [NIHSS] > or = 4 points deterioration), and mortality at 3 months. More patients had favourable outcome with the rt-PA-treated group than with the control group (64.79% vs. 22.54%; p = 0.0001). The greater proportion of patients left with minimal or no deficit 90 days after rt-PA treatment, as compared with the control group. In the treated group symptomatic intracranial hemorrhage occurred in 1 patient who recovered to a level of functional independence, and asymptomatic intracranial hemorrhage was observed in 2 patients. Our experience of an acute stroke thrombolysis service shows that we are able to provide this treatment safely and in accordance with established treatment guidelines. We recommend thrombolytic treatment in acute ischemic stroke for selected population.

Drug-induced aseptic meningitis, sensorineural hearing loss and vestibulopaty.

We report clinically rare and serious adverse reactions that occurred after the co-administration of ranitidine, ibuprofen and ciprofloxacin: completely reversible aseptic meningitis and irreversible bilateral sensorineural hearing loss, tinnitus, and vestibulopathy. Recurrent urinary inflammations treated with antibacterials, classic familial migraine, and allergy to trimethoprim-sulfamethoxazole and chromium were favourable predisposing factors for the adverse event in this patient. A close chronological relation between administration of drugs (especially ibuprofen) and adverse reactions was noted. No evidence of infection and/or autoimmune disease was found. The mechanism of these serious events may be explained as a hypersensitive reaction affecting the meninges and, partially, cochlea.

The town of Cabar, Croatia, familiar pseudocluster for multiple sclerosis--descriptive epidemiological study.

Previous descriptive surveys in the town of Cabar, Croatia carried out by our own epidemiological research group, have established that this area is at high risk for MS. To confirm the above assumption and to update MS frequency in this area we conducted a community-based intensive prevalence and incidence study. On December 31st 2001, the average prevalence was 205.7 per 100,000 with prevailing age-specific prevalence in the group of patients between 30 and 49 years of age. The average incidence (1948-2004) was 5.52/100.000 population per year (95% CI = 3.27-8.72), average mortality in the year was 2.76/100 000 inhabitants (95% CI = 1.26-5.24). Sexual index stood at 1:11, starting time was 10:04 +/- 28.53 in the year, and the average duration of the disease to the prevalence 11:11 +/- 27.26 years.

The town of Cabar, Croatia, a high risk area for multiple sclerosis--analytic epidemiology of dietary factors.

Multiple sclerosis (MS) is demyelization disease of central nervous system of unidentified causes. Analytic epidemiological research of 19 patients, clinically approved cases of MS and 25 controls, autochthonic inhabitants of town of Cabar, Croatia, the high-risk zone for the disease, was made. The research plan included case-control investigation--the "door to door" questionnaire--about nutrition habits. An odds ratio (OR) was calculated for all the factors which were more frequently found in the patients than in the controls, and vice versa. The variables that were connected with significant risk for MS in the town of Cabar included: alcohol consumption (p = 0.05), animal fats/dried meat products consumption (p = 0.007), nitrate salting (p = 0.03), strong spices (p = 0.007), mixed bread (p = 0.002), oat and oat products consumption (p = 0.0075). No connection was found with regular consumption of vegetables and fruit (p = 0.009), blue fresh fish (p = 0.028), other fresh fish (p = 0.03), freshwater fish (p = 0.002), canned fish (p = 0.004), dormouse meat (p = 0.007), air-dried meat products (p = 0.004) and using the water from water supply (p = 0.011). In the town of Cabar nutritional customs, primarily food rich in animal fats, alcohol-abuse, and oat consumption could have an influence on MS pathogenesis in genetically inclined individuals.

[Adverse effects and interactions of fluoroquinolones]. / Nuspojave i interakcije fluorokinolona.

Floroquinolones are derivatives of nalidixic acid that act as a large-spectrum antibiotics. Adverse effects and interactions of the particular fluoroquinolone depend on its chemical structure and, often, on predisposing factors in patients, including the age, hidden or previous neurological diseases, metabolic disturbances, and allergies. The adverse effects do not significantly differ among different fluoroquinolones. They can be considered as mild, moderate and severe, and their incidence is irrespective of the gender. They can occur even after the short-term administration of these antibiotics, and usually vanish after diminishing the dose or cessation of the therapy in 24-48 hours. The adverse effects can affect nervous, digestive, urinary, cutaneous, musculo-skeletal, cardiovascular, and immune system. Rarely, fluoroquinolones can harm the spermatogenesis. Their use is not advised during pregnancy due to their possible teratogenic effects. Fluoroquinolones can interact with a variety of drugs: antacides, non-steroid antirheumatics, xantines, warfarin, and others. These drug combinations often occur during the therapeutic process in the clinical practice. The incidence of adverse effects and interactions of fluoroquinolones are low; however they can result in serious complications. The post-marketing control of these antibacterial drugs is therefore highly recommended.

[Zvonimir Susic--doyen of Croatian neuropsychiatry in the 20th century]. / Zvonimir Susic--velikan hrvatske neuropsihijatrije 20. stoljeca.

There are three distinct phases in the life of Zvonimir Susic--neurologist, psychiatrist, forensic expert, educator, teacher, translator, and erudite of general and professional knowledge--Zagreb, Rijeka and Zadar phase. In Zagreb (1926-1946) he was promoted to physician (1932), there he was a student tutor, then the assistant at the Physiology Institute of the Medical Faculty; volunteer, hospital doctor (he got the specialization in 1938), assistant and head doctor of the Hospital for Mental Diseases in Vrapce, and the assistant professor (1941) at the Neuropsychiatric Department of the Zagreb University. In Rijeka (1947-1959) he reorganized Psychiatric and established the Neurology Department of the General Hospital "Brothers Dr. Sobol" and, at first, he was the honorary professor, then assistant professor and associate professor of neurology and psychiatry at the Medical Faculty of Rijeka. In Zadar (1960-1968) he was the manager of the Ugljan Hospital. He published approximately 100 works in the field of clinical neurology, neuropathology, psychiatry, and forensic psychiatry, His works on cortical presentation of the body scheme, hallucinations, tuberous sclerosis, pregnancy and multiple sclerosis, pathohistology of demyelisation, toxic neuritis, epilepsies, nervous manifestations of Malta fever, herpetic infections, pathogenesis of convulsive syndromes, psychiatric terminology, therapies of Parkinson disease and schizophrenia, ability of making will, organization of the psychiatric service, were published in national and prestigious European journals, and often cited. He wrote chapters in psychiatric handbooks and special notes in encyclopedic editions. Together with Stanislav Zupic he was the author of the first and only psychodrama in Croatia. He was one of the pioneers of neuropathology in Croatia because he founded the Neuropathology Laboratory in Vrapce Hospital in 1936. He had a remarkable preciseness in examining the patient. He was frequent and imaginative lecturer in various sections in Croatian Medical Association and other public institutions. As a gifted polyglot he was occupied by the translation work when retired. In our, till then Middle-European culture-oriented medical area, he introduced values and patterns of French neurological and German neuropathological schools.