Clinical Neuroscience

[Efficacy of anticoagulation with vitamin K antagonists in acut stroke patients with atrial fibrillation - Hungarian results]

SAS Attila, CSONTOS Krisztina, LOVÁSZ Rita, VALIKOVICS Attila

JANUARY 30, 2015

Clinical Neuroscience - 2015;68(01-02)

[Background and objective - An estimated 20% of ischemic strokes are of cardiogenic origin, half of which is associated with atrial fibrillation (AF). Anticoagulation treatment of patients with this arrhythmia reduces their risk of stroke. Effectiveness and safety of oral anticoagulant therapy with vitamin K antagonists (VKA) is limited, however, by their well-known narrow therapeutic window and the substantial inter- and intraindividual variability of INR values depending on genetic and dietary factors as well as drug interactions. Our objective was to evaluate the prevalence of adequate anticoagulation and the level of anticoagulant effect actually achieved among patients with AF hospitalized for acute stroke. Methods - Patients with AF admitted to our hospital ward in 2012 for acute stroke (n=226) were included in the analysis. Using descriptive statistics, relevant clinical and therapeutic characteristics of the patients were assessed, with special reference to the INR values on admission (among patients with known AF), and the clinical outcomes. Results - Of the study cohort, 170 patients had a diagnosis of AF before the admission for stroke, but 47% of them did not take anticoagulants. Patients who suffered stroke while on anticoagulants (83 on VKA, 7 on low-molecular-weight heparins), were in most cases (75%) out of the therapeutic INR range, typically undertreated (INR<2). Overall, inadequate or completely absent anticoagulation was documented in 81% of the stroke cases occurring in patients with known AF. Of the entire study cohort, 41% was discharged home, 34% required continued institutional care, and 25% died. Conclusions - The inadequacy or lack of anticoagulation was observed in the vast majority of acute strokes in patients with known AF. These cases are often related to the well-documented limitations of VKA therapy in terms of its safety, tolerability and/or practical aspects. To prevent them, important changes are warranted in the anticoagulation practice, including the closer control of VKA therapy and the broader use of new oral anticoagulants.]

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Clinical Neuroscience

[Greetings]

RAJNA Péter, TAJTI János

Clinical Neuroscience

[Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate]

MATOLCSI Judit, RÓZSA Csilla

[Dimethyl fumarate (DMF) is a novel oral therapy that has recently been approved for the treatment of relapsing- remitting multiple sclerosis (RRMS). Dimethyl fumarate shows anti-inflammatory and cytoprotective properties that are thought to be mediated primarily via activation of the nuclear factor (erythroid-derived 2)-like 2 - Nrf2 transcriptional pathway, which up-regulates the genes involved in the cellular response to oxidative stress. The drug was evaluated in 2 large, randomized, double-blind, multicentric, multinational, 2-year, phase III clinical trials. The DEFINE and CONFIRM trials, conducted with over 2600 adult patients suffering from RRMS, unequivocally confirmed the efficacy of DMF (2×240 mg daily) in reducing the annualized relapse rate (ARR) and reducing the proportion of patients with MS relapse at 2 years. Significantly reduced sustained disability progression was observed with the drug versus placebo in DEFINE, while the same tendency was seen in CONFIRM. The MRI results of the studies were also convincing: DMF significantly reduced the number of new/enlarging T2-hyperintense lesions and the number of Gd-enhancing lesions compared to placebo. Dimethyl fumarate was generally well tolerated and no safety concern has been raised. Adverse events that occurred most frequently included flushing and gastrointestinal events. The long- term efficacy and tolerability of dimethyl fumarate is currently being investigated in the ENDORSE trial, with interim results demonstrating the same results as the two previous studies. In conclusion, although further, mostly comparative data are needed to fully establish the relative efficacy and tolerability of dimethyl fumarate compared with other therapies, dimethyl-fumarate is a valuable addition to the therapeutic options available for RRMS.]

Clinical Neuroscience

[Role of modified open-door laminoplasty in the treatment of multilevel cervical spinal stenosis: a retrospective analysis of 43 cases]

VITANOVICS Dusan, BÁRÁNY László, PAPP Zoltán, PADÁNYI Csaba, BALOGH Attila, BANCZEROWSKI Péter

[Background and purpose - Symptomatic degenerative multilevel cervical spinal stenosis - beside other methods - is often treated using the open-door laminoplasty. This procedure aims to decompress the spinal cord and preserve the stability of the cervical spine. The efficiency and safety of the method was proved by numerous Japanese and American studies, also the technique related complications are well known. We treated 43 patients with symptomatic multilevel cervical spine stenosis using the open-door laminoplasty as a surgical procedure of choice in the National Institute of Clinical Neurosciences between 2009 and 2012. In this article we analyse our results and the related literature is discussed. Methods - Symptomatic patients with a minimum of three-segment cervical spine stenosis and radiologically proved myelopathy or with electrophisiologically verified subclinical myelopathy were selected for laminoplasty. Patients in whom cervical kyphosis was present were operated on using laminectomy and posterior fusion. Postoperative control CT, MRI and/or X-ray images were made after the surgery and at six weeks, three, six and 12 months after the operation and in the same time neurological evaluation was performed. The modified Japanase Orthopaedic Association (mJOA) scale value was assigned to patients preoperatively, six weeks, three, six and 12 months after the operation. The statistical difference between the groups of data was tested by chi square test. Results - The average follow-up time was 27 months (minimum seven, maximum 42). According to the mJOA scale, 26 patient’s condition (61%) improved, in 13 cases (30%) remained unchanged, and in one case (2%) we detected neurological deterioration. We lost three patients during the follow up period. The median of mJOA preoperatively was 12 (minimum eight, maximum 18), while six week postoperative mJOA was 14 (minimum 10, maximum 17). Three, six and 12 months mean value of mJOA was 14 which shows that the improvement in patients’ condition remained stable at one year after surgery. The difference was statistically significant (p<0.05). The canal’s average anteroposterior diameter on CT was 8.29±0.92 mm at the level of C III, while after the operation we measured 15.16±1.02 mm; 7.54±0.62 mm at the level of C IV before, and 15.29±0.2 mm after; 9.05±0.48 mm at the level of C V before and 17.23±0.4 mm after the surgery. The differences proved to be significant (p=0.0001). Conclusion - According to our experiences the modified open-door laminoplasty is an efficient and safe method for the treatment of symptomatic multilevel cervical spinal stenosis.]

Clinical Neuroscience

[The efficacy of lacosamide in relation to antiepileptic drug history. Clinical experiences in adult partial epilepsy]

BARCS Gábor, SZŰCS Anna, HORVÁTH András, KAMONDI Anita

[Objective - A retrospective study in adult partial epilepsy on the efficacy of lacosamide in relation to previous antiepileptic drug experiences. Method - We analysed 3-65 months’ data on epilepsy-care of 43 pharmacoresistant partial epilepsy patients treated with lacosamide. Further analysis of antiepileptic drug history was carried out in strictly selected subgroups of patients with good and poor therapeutic response to lacosamide (10 and 9 patients, respectively) for 2-10 years long retrospective follow up. Patients - Adult patients with partial-onset seizures had been treated previously with three or more lifetime antiepileptic drugs without permanent success. Results - Six patients (14%) were seizure free, eleven patients (25%) have experienced important improvement (their seizure-frequency decreased by at least 50%) for more than 12 months. Fourteen patients (32%) improved for less than 6 months and then have relapsed; and add-on lacosamide proved ineffective in 12 patients (28%). Those selected 10 patients successfully treated with lacosamide (seizure free for at least six months) favourably responded to carbamazepine or oxcarbazepine earlier and levetiracetam was ineffective or even caused worsening. The selected lacosamide-unresponsive nine patients responded unfavourably to carbamazepine or oxcarbazepine earlier. Fifteen patients (35%) suffered side effects as dizziness or sleepiness, in 11 of them lacosamide was combined with a „traditional” sodium-channal blocker antiepileptic drug. Conclusion - Lacosamide is an effective add-on antiepileptic drug in difficult-to treat adult partial epilepsy patients. Our data suggest that good lacosamide response may be expected in those patients who reacted favourably to „traditional” sodium-channel blocker carabamazepine or oxcarbazepine earlier.]

Clinical Neuroscience

[Assessment of severity and time course of critical illness neuropathy in septic patients: a prospective observational study]

NEMES Réka, FÜLEP Zoltán, LÁSZLÓ István, SÁRKÁNY Péter, FEKETE Klára, MECHLER Ferenc, FÜLESDI Béla

[Objective - In this prospective observational study we investigated electrophysiological alterations in the early phase of critical illness and correlated electrophysiological findings with the clinical picture and outcome. Methods - We enrolled 21 critically ill surgical patients having ≥12 Acute Physiology and Chronic Health Evaluation (APACHE) II scores on admission. Routine non-invasive bilateral electroneurography (ENG) examination of median and ulnar nerves was done on five consecutive days starting in two days after admission. Then weekly follow-up was performed. Motor and sensory nerve conduction indices were calculated and correlated with APACHE II and Simplified Acute Physiology Score II severity scores. Results - On the first examination 18/21 patients had >20% reduction in the motor and sensory nerve conduction indices. Severity score systems showed significant negative correlation with the daily change of CMAP and SNAP amplitudes and calculated nerve conduction indices (Spearman’s correlation, p<0,001). Mortality was higher in the patients with worse admission ENG and/or stagnant electrophysiological status or declining tendency in the first week. Conclusions - Electrophysiological alterations appeared soon after the development of critical illness. Early phase alterations showed a strong correlation with patients’ general condition and more severe electrophysiological alterations predisposed to higher mortality. In several cases early alterations proved to be reversible. ]

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[The Comprehensive Aphasia Test in Hungarian]

ZAKARIÁS Lilla, RÓZSA Sándor, LUKÁCS Ágnes

[In this paper we present the Comprehensive Aphasia Test-Hungarian (CAT-H; Zakariás and Lukács, in preparation), an assessment tool newly adapted to Hungarian, currently under standardisation. The test is suitable for the assessment of an acquired language disorder, post-stroke aphasia. The aims of this paper are to present 1) the main characteristics of the test, its areas of application, and the process of the Hungarian adaptation and standardisation, 2) the first results from a sample of Hungarian people with aphasia and healthy controls. Ninety-nine people with aphasia, mostly with unilateral, left hemisphere stroke, and 19 neurologically intact control participants were administered the CAT-H. In addition, we developed a questionnaire assessing demographic and clinical information. The CAT-H consists of two parts, a Cognitive Screening Test and a Language Test. People with aphasia performed significantly worse than the control group in all language and almost all cognitive subtests of the CAT-H. Consistent with our expectations, the control group performed close to ceiling in all subtests, whereas people with aphasia exhibited great individual variability both in the language and the cognitive subtests. In addition, we found that age, time post-onset, and type of stroke were associated with cognitive and linguistic abilities measured by the CAT-H. Our results and our experiences clearly show that the CAT-H provides a comprehensive profile of a person’s impaired and intact language abilities and can be used to monitor language recovery as well as to screen for basic cognitive deficits in aphasia. We hope that the CAT-H will be a unique resource for rehabilitation professionals and aphasia researchers in aphasia assessment and diagnostics in Hungary. ]

Clinical Neuroscience

The applications of transcranial Doppler in ischemic stroke

FINNSDÓTTIR Herdis, SZEGEDI István, OLÁH László, CSIBA László

Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

Clinical Neuroscience

Hyperhomocysteinemia in female migraineurs of childbearing ages

ALEMDAR Murat, SELEKLER Macit Hamit

Background and purpose - Migraine is a risk factor for ischemic stroke in women of childbearing ages. Previous researches revealed a higher prevalence of hyperhomocysteinemia in migraineurs. Possible differences on the frequencies of hyperhomocysteinemia between migraine with aura and migraine without aura could contribute the established variances in stroke risk between these migraine types. Therefore, we aimed to search if the frequency of hyperhomocysteinemia was different between these subtypes of migraine or not. Methods - We analyzed the findings of serum homocysteine levels in female migraineurs of 16-49 years old who admitted to our outpatient clinic. Results - Homocysteine level was elevated in 13.3% of study population. There were not any significant differences on median serum homocysteine levels between migraine with aura (8.0 mikromol/L) and without aura (8.5 mikromol/L). (p=0.426) The frequencies of hyperhomocysteinemia were also similar (9.1% versus 16.7%, respectively; p=0.373). Correlation analyses did not reveal any linear correlation between ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura (p=0.417 and p=0.647, respectively). Similarly, any linear correlation between disease ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura was not detected (p=0.359 and p=0.849, respectively). Conclusion - The median serum homocysteine levels and the frequencies of hyperhomocysteinemia are similar between migraine with aura and without aura in women of childbearing ages. Therefore, the variances on stroke risk ratios between these types of migraine are probably not originated from the differences of serum homocysteine status.

Clinical Neuroscience

[Hypertension and it’s therapy in acut phase of stroke]

KÁPOSZTA Zoltán, RÁCZ Klára

[The elevation of blood pressure above normal and premorbid values within the first 24 hours of symptom onset in patients with stroke is relatively common. This acute hypertensive response is usually managed by different group of physicians, including general practitioners, emergency physicians, neurologists, internists, intensivisists. Management strategies of this phenomenon vary considerably. The first consideration in blood pressure management in this clinical setting is to determine whether the patient might be a candidate for thrombolytic therapy. For those patients are not entitled to that therapy premorbide blood pressure values and the type of stroke are the key data for sufficient control of hypertension. In patients with chronic hypertension, the lower end of the autoregulation curve is shifted toward high pressure and an impaired autoregulation due to acute stroke may increase the risk for further brain tissue damage if the blood pressure is inadequately controlled. The current guidelines recommend lowering blood pressure in patients with an intracranial haemorrhage below 160- 180/100-105 mmHg, if the patient is normotensive, while the target level is 180/105 mmHg in hipertensive patients. However, in ischaemic stroke no treatment is recommended if systolic blood pressure <220 mmHg and/or diastolic blood pressure <120 mmHg in the acute stage. Clinical studies are rare which assess the effectiveness of different antihipertensive drugs in acute stroke. The first strong evidence came from the ACCESS (The Acute Candesartan Cilexetil Therapy in Stroke Survivors) trial which suggested that a 7-day course of candesartan after an acute ischaemic stroke significantly improves cardiovascular morbidity and mortality.]

Hypertension and nephrology

[Hypertension and atrial fibrillation. Part 1. - Epidemiological data. The pathomechanism of PF in hypertension]

KÉKES Ede

[Atrial fibrillation (PF) is the most common arrhythmia on the basis of analyzes conducted in different regions of the world. The main reason for this is the aging of the population. High blood pressure is one of the major factors of mortality in both developed and poor economical countries. The combined presence of the two diseases presents many hazards to our body. The most significant of these is the development of thromboembolic stroke, which is constantly increasing with age. The author analyzes in detail the aetiology called atrial cardiomyopathy, behind which there are complex structural, architectural, contractile and electro-physiological changes and leads to clinical manifestation of PF.]