Comorbidities in Patients with Multiple Sclerosis in Croatia.

BACKGROUND: Comorbidities in multiple sclerosis (MS) have a big role in management of this chronic demyelinating neurodegenerative disorder. The aim of this study was to evaluate comorbidities in patients with MS in Croatia. SUBJECTS AND METHODS: This was a prospective cross-sectional study carried out in an out-patient setting at a tertiary healthcare centre over 10 months, which included 101 consecutive patients with MS (mean age 42.09 (range 19-77) years, 75 female, 26 male, EDSS score 3.1 (range 0.0-7.0)). The average duration of the disease was 13.5±7.487 (range 1-42) years. Thirty-six patients were treated with disease modifying therapies (DMTs). Information on comorbidities was obtained during the medical interview. Data was analysed using software package IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. RESULTS: 33% (n=34) patients did not have any comorbidities, and there is an equal number of patients (n=34, 33%) that just had one comorbidity. 17.6% (n=18) of patients had two comorbidities, and 15.7% (n=16) three or more comorbidities. The most frequent comorbidity was depression found in 25 (24.75%) patients (19 (18.8%) women, 6 (5.9%) men), followed by the hypertension in 12.87% (n=13). Hyperlipidemia and migraine were each found in 6.93% (n=7), and hypothyreosis and arrhythmia each in 3.96% (n=4). The number of the comorbidities was found to significantly increase with the duration of MS (r=0.232, p=0.037). Women were found to have significantly bigger numbers of comorbidities than men (t=-2.59, df=74, p<0.05). Older patients with MS were found to have significantly more comorbidities (r=0.335, p<0.01). CONCLUSIONS: This study gives insight into the presence of comorbidities in Croatian patients with MS. Connection with comorbidities must be considered when managing patients with MS. Any other comorbidity in MS may also affect the condition of the patient in general, and also their quality of life, and requires a tailored approach in management.

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study.

RATIONALE: Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates. OBJECTIVES: To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy. METHODS: Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling. RESULTS: Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77). CONCLUSION: Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

Choline and N-acetyl aspartate levels in the dorsolateral prefrontal cortex at the beginning of the recovery phase as markers of increased risk for depressive episode recurrence under different duration of maintenance therapy and after it: a retrospective cohort study.

AIM: To evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression. METHODS: This retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model. RESULTS: NAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery. CONCLUSION: Patients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients.

Clinical trials in developing countries - ethical considerations.

When designing clinical trial or considering decision to take part in particular clinical trial as investigators, even before submission to responsible Central Ethic Committee, we always make certain private assessment about ethical justification of this clinical trial. When making assessment if any clinical trial is ethically justifiable, there should make no difference in which country this clinical trial will be executed. Physicians coming from developing countries must ensure that patient population of developing countries is not misused in any ethically questionable clinical trial. There must be careful assessment of clinical protocols by various independent local advisory committees (e.g. hospital review boards, hospital drug committees, hospital administration and whatever is applicable) to exclude the possibility that only one person or one group of people has concentrated power to make decisions for entire country. Many times physicians/clinical researchers from developing countries are faced with the criticisms that they are not of the same quality as physicians from developed countries and that they can be easily bribed by sponsors, which are based on the prejudice that any clinical trial can be executed in developing countries, no matter of quality or risks for patients. Physicians coming from developing countries must ensure that patient population of developing countries is not misused in any ethically questionable clinical trial.

Many Faces of Déjà Vu: a Narrative Review.

French expression standing for the phrase "already seen" is a déjà vu. It is thought that as much as 97% of the population have experienced déjà vu at least once in their lifetime and 67% experience it regularly. The explanations of this phenomenon in novels and poems include reincarnation, dreams, organic factors, and unconscious memories. In this narrative review connection between déjà vu and various other conditions has been mentioned: false memories, temporal lobe epilepsy and other neurological conditions. In psychiatric patients déjà vu phenomenon is more often seen in patients with anxiety and people with derealisation/ depersonalization. It seems that temporal region is the origin of déjà vu phenomena in both healthy individuals and in individuals with neurological and psychiatric conditions, but the exact mechanism of this phenomenon is however still unknown. More attention should also be given to déjà vu from philosophical and religious perspectives as well. Déjà vu is still an enigma which could only be revealed with multidisciplinary approach through cooperation between neurologists, brain scientists, psychiatrists and experimental psychologists.

Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy. METHODS: 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later. RESULTS: Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio. CONCLUSION: Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.

Trigeminal neuralgia--case and treatment analysis at the Department of Oral Surgery of the University Hospital Dubrava.

The aim of the study was to explore certain risk factors for trigeminal neuralgia (TN), assess the prevalence of misdiagnoses of TN made by primary care dentists, compare the treatment practice for TN at the Department of Oral Surgery with the guidelines, and the importance of interdisciplinary approach in TN treatment. The study included 237 patient records (70 men and 167 women, aged 5-91 years) referred to the Department under the diagnosis of TN. From their medical records, demographic data, referral diagnose, clinical diagnose, additional diagnostic procedures and treatment were analysed. Neuralgia of the trigeminal nerve affects predominantly elderly female population, while the impact of the season on the incidence of the disease has not been determined. The most common therapy used at the Department were blockades, carbamazepine or their combination. 63.3% patients were referred for further diagnostic tests following the first examination. The number of misdiagnosed cases referred by primary care dentists (33.6%) points that better training in diagnosing TN is needed for the dental practitioners. The treatment methods at the Department need to be harmonized with the latest guidelines on neuralgia treatment. Due to the complexity of etiological factors, an interdisciplinary approach is necessary.

Primary total hip arthroplasty: health related quality of life outcomes.

PURPOSE: The health related quality of life (HRQoL) outcomes of total hip arthroplasty (THA) present a pertinent and clinically important problem in modern orthopaedics. Our goal was to report and compare the health-related outcomes after THA in respect to type of fixation in patients with hip osteoarthritis (H-OA) one year after operation. METHODS: A total of 145 patients with H-OA who received THA were evaluated. Uncemented and cemented subjects were evaluated using generic measures, i.e. the EQ-5D questionnaire, and the disease-specific measures designed by the authors, i.e. the Total Hip Arthroplasty Questionnaire (THAQ). Obtained data was statistically processed at the level of pain, functionality and general health perception. Patient-reported outcomes were measured differences between pre-operative measures and those at one-year follow-up visit. RESULTS: Significant improvement in health outcomes was reached in both groups regardless of the type of fixation (p < 0.001). Uncemented fixation exhibited better results for EQ-5DINDEX, pain (p = 0.004) and self-care on EQ-5D (p = 0.043), as well as increased magnitude of change for functionality on THAQ (p = 0.002). However, additional analysis of the subset did not reveal a significant difference between cemented vs. uncemented groups with regard to function on THAQ, but the significant difference on self-care and pain dimensions of EQ-5D remained. CONCLUSIONS: Uncemented endoprosthesis generally achieved better short-term outcomes in some dimensions. However, painless mobility has been restored in most of the patients, regardless of the fixation type. Both methods reached good clinical outcomes in their respective domains; therefore, we would emphasise prevention of osteoarthritis and the quality of care as the more important predictors of good clinical outcomes.

Signal hyperintensities on brain magnetic resonance imaging in patients with primary Sjögren syndrome and frequent episodic tension-type headache: relation to platelet serotonin level and disease activity.

OBJECTIVE: To examine differences in number and size of signal hyperintensities (SH) on magnetic resonance imaging (MRI) between patients with primary Sjögren syndrome (pSS) and controls who all had frequent episodic tension-type headache (FETH), and to investigate their relation to platelet serotonin level (PSL), patient age, disease duration, and activity. METHODS: SH in 22 pSS patients with FETH were compared to 20 aged-matched controls with FETH, using the modified semiquantitative rating scale. Spectrofluorimetry was used for determination of PSL, and the European League Against Rheumatism SS Disease Activity Index (ESSDAI) for disease activity assessment. RESULTS: Statistically significant differences in the total number of SH were noted infratentorially (p = 0.025) and in the basal ganglia for lesions of diameter > 5 mm (p = 0.048). Significant correlations were found between disease duration and number of overall lesions > 5 mm (p = 0.04) and subcortical lesions of diameter 2-5 mm (p = 0.035). Number of periventricular SH inversely correlated to PSL (p = 0.019) and to patient age (p = 0.004), without association with markers of immunoinflammation and ESSDAI. CONCLUSION: Our study showed that SH on brain MRI are more common in specific regions of the brain in pSS patients with FETH than in controls with FETH, signifying a more widespread cerebral vasculopathy in SS patients with FETH. Periventricular SH seem to be associated to increased platelet serotonin release in pSS patients with FETH and correlated with disease duration, without correlation to the actual ESSDAI and markers of immunoinflammation, and might be linked with chronic immunoinflammation of low-grade intensity and vasculitis in pSS.

Platelet serotonin in primary Sjögren's syndrome: level and relation with disease activity.

Primary Sjögren's syndrome (pSS) is chronic autoimmune disorder of unknown ethiopathogenesis. In line with the concept of neuroimmunohormonal dysregulation in inflammatory rheumatic diseases, the aim of this study was to investigate platelet serotonin level (PSL) in patients with pSS and its relation with the activity and duration of the disease. Significantly lower PSL in pSS patients (N=61) was shown as compared to healthy controls (N=103). No correlation was found between PSL and the actual disease activity assessed by the recently developed EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results suggest involvement of the serotonin system in the pathogenesis of pSS.

Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB).

Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection, other neurologic complications may occur, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panicc attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome. We describe here a patient with a triad of unusual symptoms in chronic LNB including tremor, seizures and psychosis. Standardized medical interview, neurologic examination, neuroimaging, serum and CSF serology as well as EEG and EMNG evaluation were performed. The patient was treated with intravenous ceftriaxone and doxycycline and responded with rapid clinical and functional improvement.Newertheless, he suffered from multiple systemic and neurologic sequelas that influenced his daily activities in post treatment period. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating diagnosis, early treatment and the uncertainties concerning the sequelae after treatment. In patients with non-specific long lasting symptoms in the absence of overt clinical signs suggesting CNS involvement, routine treatment with i.v. ceftriaxone is not to be encouraged.

Coexistence of intradural spinal arteriovenous malformation and associated developmental anomalies - report of two cases.

Spinal arteriovenous malformations (AVM) have been devided into dural (Type I), intramedullary glomus (Type II), juvenile (Type III), and perimedullary direct arteriovenous fistulae (Type IV). AVMs are usually associated with subacute myelopathy in what has been known as Foix-Alajouanine syndrome. We presented two patients with two intradural spinal arteriovenous malformations associated in what we call Foix-Alajouanine syndrome. The both patient developed acute back pain and paresthesias, followed by paraplegia and incontinence. The clinical status of one patient has been improved after particle embolization for a 17 years when he deteriorated up to paraplegia after spinal angiography for follow up. Clinical status in another patient deteriorated, because particle emoblisation cannot be performed due to very descrete presentation of the feeding artery. Extensive neuroradiological examination in both patients revealed coexistence of numerous associated developmental anomalies in both patients. We conclude that arteriovenous malformations occasionally are associated with other vascular and nonvascular developmental anomalies elsewhere in the body. These findings rise attention about keep in mind the suspicion of mutual etiopathogenesis and congenital origin of these anomalies. Early timing of the diagnostic and therapeutic interventiosn are stressed to prevent or delay irreversible ishaemic myellopathy or haemorrhage. For the definitive diagnosis of spinal arteriovenous malformations and evaluation of its occlusion grade after the therapy spinal angiography is needed

Fragile X-premutation tremor/ataxia syndrome (FXTAS) in a young woman: clinical, genetics, MRI and 1H-MR spectroscopy correlates.

It is generally thought that fragile X-associated tremor/ataxia syndrome (FXTAS) represents a late-onset neurodegenerative disorder occuring in male carriers of a premutation expansion (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR 1) gene. However, several female patients with FXTAS have also been reported recently. Here, we describe a 23-year old woman with positive family history of mental retardation and autism who presented clinically with action tremor, ataxia, emotional disturbances and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain showed diffuse cortical atrophy, while 1H-MR spectroscopy (MRS) revealed decreased levels of N-acetylaspartate (NAA) in the cerebellum, basal ganglia, and pons. Genetic testing confirmed heterozygous FMR 1 gene premutation of 100 CGG repeats in the abnormal allele and 29 CGG repeats in the normal allele. We concluded that FXTAS may be an under-recognized disorder, particularly in women.

Symptomatic capillary telangiectasia of the pons and intracerebral developmental venous anomaly - A rare association.

Various combinations of vascular malformations of the brain in one lesion have been reported, while others seem to be very rare. In this report, the authors discuss the case of a coexistence of an capillary telangiectasia of the pons and intracerebral venous anomaly. To our knowledge, this is the first report of coexistence of a capillary telangiectasia of the pons and intracerebral venous anomaly apparted from each other. These discrete vascular malformations of the brain raise attention on possible interrelations in the pathogenesis of these entities. We report a case of pontine capillary telangiectasia and intracerebral venous anomaly in a 42-year-old woman with a right side facial palsy. Hight field magnetic resonance imaging suggested presence of a capillary telangiectasia of the pons. Another lesion in the left frontal gyrus was attributable to the venous anomaly. Along with neuroradiological findings, results of the somatosensor evoked potentials, brain stem auditory potentials, laboratory analysis including blood, cerebrospinal fluid and urine investigation are demonstrated. Awareness of the magnetic resonance imaging finding of the capillary telangiectasias and of the venous anomalies may help in defining clinical correlates of this vascular malformations, while the follow up of these malformations might help to asses risk of vascular rupture. We and others previously selects capillary telangiectasia and venous anomaly in two discrete entities. Coexistence of these malformations in the brain apparted from each other appear to be very rare and raise attention on possible interactions in their natural history and pathogenesis.