Screening for C9orf72 Expansion Mutation in Serbian Patients with Early-Onset Dementia.

BACKGROUND: Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia (EOD), characterized by behavioral changes (behavioral variant; bvFTD) or language deficits. A hexanucleotide repeat expansion in a noncoding region of chromosome 9 open reading frame 72 (C9orf72) has been proved to be a major cause of both familial and sporadic amyotrophic lateral sclerosis or FTD, with or without concomitant motor neuron disease (MND). METHODS: The aim of this study was to assess the frequency of the C9orf72 hexanucleotide expansion in a cohort of 117 Serbian patients with EOD and to report phenotypic features of identified carriers. RESULTS: We identified 4 of 117 (3.4%) patients with EOD to have C9orf72 hexanucleotide expansions. All patients were classified in the FTD disease spectrum group (8.2%): 3 patients fulfilled the criteria for bvFTD, and 1 patient had FTD-MND. None of the patients with the C9orf72 hexanucleotide expansion fulfilled the diagnostic criteria for language variants of FTD, FTD-progressive supranuclear palsy overlap syndrome, dementia with Lewy bodies or Alzheimer's dementia. CONCLUSION: In a cohort of consecutive patients with EOD, 3.4% had the C9orf72 hexanucleotide expansion with clinical phenotypes of bvFTD or an overlap of bvFTD and MND.

Sonothrombolysis: is the story (t)old or just the beginning.

INTRODUCTION: Intravenous administration of recombinant tissue plasminogen activator, fastest and widely feasible treatment in acute ischemic stroke induces arterial recanalization, a prerequisite for neurological recovery. THE THERAPEUTIC ROLE OF ULTRASOUND AND POTENTIAL MECHANISM OF SONOTHROMBOLYSIS: Augmentation of recanalization can be achieved safely in combination with diagnostic transcranial Doppler by delivering mechanical pressure waves to the thrombus and exposing more thrombus surface to circulating drug. The addition of microspheres can further improve thrombolytic effect. CLINICAL TRIALS: International multicenter CLOTBUST trial showed that acute ischemic stroke patients treated with sonothrombolysis had higher rate of arterial recanalization and dramatic clinical recovery without increasing risk of symptomatic intracranial hemorrhage. A microsphere dose-escalation study called TUCSON showed that rates of recanalization and clinical recovery tended to be higher in target groups compared with controls. META-ANALYSIS OF CLINICAL TRIALS OF SONOTHROMBOLYSIS: Cochrane Stroke Group found that sonothrombolysis was likely to reduce death or dependency. A meta-analysis of sonothrombolysis showed that patients who received any form of sonothrombolysis had more than twofold higher likelihood of achieving complete arterial recanalization. PERSPECTIVES FOR SONOTHROMBOLYSIS - OPERATOR-INDEPENDENT DEVICE FOR SONOTHROMBOLYSIS: The collaborative group of the CLOTBUST trial designed multi-transducer assembly to cover conventional windows used for transcranial Doppler examinations. Operator-independent device can be quickly mounted by medical personnel with no prior experience in ultrasound. Sonothrombolysis for acute ischemic stroke is now tested in a pivotal efficacy multi-national trial called CLOTBUSTER. CONCLUSION: Ultrasound is a promising tool to enhance systemic thrombolysis.

Deep brain stimulation in psychiatry.

INTRODUCTION: Deep brain stimulation is a stereotactic neurosurgical method used in the treatment of Parkinson's disease and some other movement disorders. The application of deep brain stimulation in the treatment of certain psychiatric disorders has been intensively investigated taking into account the current knowledge of neurobiological basis of mood regulation, cognition, and behaviour. This paper has been aimed at presenting the available data on experience in the application of deep brain stimulation in the treatment of psychiatric disorders. It gives an overview of scientific and professional literature, bearing in mind all the contemporary approaches in the treatment of certain psychiatric disorders. Research results available so far in the treatment of treatment-resistant depression, obsessive-compulsive disorder, Gilles de la Tourette syndrome, addiction and Alzheimer's dementia, are affirmative concerning the efficacy of the method and low risk of adverse effects. Deep brain stimulation, as a relatively new neurosurgical method in the treatment of psychiatric disorders, is being intensively developed, and it is certainly going to be one of the treatments of choice, primarily of treatment-resistant disorders.

Cognitive impairment in multiple system atrophy: a position statement by the Neuropsychology Task Force of the MDS Multiple System Atrophy (MODIMSA) study group.

Consensus diagnostic criteria for multiple system atrophy consider dementia as a nonsupporting feature, despite emerging evidence demonstrating that cognitive impairments are an integral part of the disease. Cognitive disturbances in multiple system atrophy occur across a wide spectrum from mild single domain deficits to impairments in multiple domains and even to frank dementia in some cases. Frontal-executive dysfunction is the most common presentation, while memory and visuospatial functions also may be impaired. Imaging and neuropathological findings support the concept that cognitive impairments in MSA originate from striatofrontal deafferentation, with additional contributions from intrinsic cortical degeneration and cerebellar pathology. Based on a comprehensive evidence-based review, the authors propose future avenues of research that ultimately may lead to diagnostic criteria for cognitive impairment and dementia associated with multiple system atrophy.

Improvement of post-hypoxic action myoclonus with levetiracetam add-on therapy: A case report.

INTRODUCTION: Chronic post-anoxic myoclonus, also known as Lance-Adams syndrome, may develop following hypoxic brain injury, and is resistant to pharmacological therapy. CASE REPORT: The patient we presented developed post-anoxic action myoclonus with severe, completely incapacitating myoclonic jerks. Myoclonus did not respond to the treatment with commonly used agents, i.e. valproate and clonazepam alone or in combination. Improvement of the action myoclonus was observed only after adding levetiracetam. CONCLUSION: Although Lance-Adams syndrome may not be fully curable at this point, levetiracetam appears to be a promising agent that can significantly improve functional level and overall quality of life of patients with this disorder.

Extrapyramidal syndromes caused by antipsychotics.

INTRODUCTION: Extrapyramidal syndromes are significant side effects of antipsychotic therapy due to their severity, frequent occurrence and complications. This paper gives a brief summary of the literature with the emphasis on epidemiology, etiology, diagnosis and differential diagnosis, as well as the treatment of extrapyramidal disorders induced by antipsychotics. DYSTONIA: Sustained muscle contractions cause twisting and repetitive movements or abnormal postures. It may appear either as an acute or delayed, i.e. tardive sign. The incidence of dystonia is 2-3% among the patients treated with antipsychotics, and 50% among the ones cured with conventional antipsychotics. AKATHISIA: The main feature of this curious adverse effect is the psychomotor restlessness and the inability to remain motionless. Although akathisia is not very frequent, its incidence and prevalence ranges from 5 to 50% among the treated patients. It is most probably a result of the blockage ofdopaminergic receptors. PARKINSONISM: The most frequent secondary Parkinsonism is the one caused by drugs. The characteristic parkinsonian signs regress 4 to 16 weeks after the discontinuation of antipsychotic therapy. In the era of atypical antipsychotics this adverse effect appears less frequently. TARDIVE DYSKINESIA: Involuntary choreatic movements may appear days and months after the introduction of continuous use of antipsychotics. The individual susceptibility may play the major role in the development of this side effect. CONCLUSION: Numerous studies have compared conventional and atypical antipsychotics as well as atypical ones with one another in order to decrease the risk of development of extrapyramical side effects as well as to prevent their occurrence and improve their treatment.

Neurosonographic monitoring of haemodynamic changes in tandem middle cerebral and internal carotid artery occlusion due to arterial dissection.

A middle-aged man with pain in the right eye and right side of the neck was brought to the emergency department one hour after the onset of left-sided weakness. Computed tomography (CT) showed hyperdense right middle cerebral artery (MCA). On transcranial Doppler (TCD), occlusion of the right MCA and right internal carotid artery (ICA) was found. Thirty minutes after thrombolytic therapy was initiated, engagement of collateral circulation through the anterior communicating artery (AComA) was shown by TCD. Caro-tid duplex examination confirmed occlusion of the right ICA with intimal flap and intramural haematoma. CT angiography revealed flame-like occlusion of the right ICA, and occlusion of the right MCA with collateral supply from the left to right anterior cerebral artery through the AComA. Recanalization of the MCA and ICA was evident on both CT and ultrasound. Frequent ultrasound monitoring is useful for haemodynamic evaluation of carotid artery dissection, while TCD plays an important role in real-time monitoring of flow changes of intracranial vasculature.

[Diagnosis and outcome of cervical artery dissection].

INTRODUCTION: Spontaneous dissection of the cervical artery is a rare non-atherosclerotic vascular disease of unknown aetiology and unclear pathogenesis that may be a cause of ischemic stroke in young adults. DIAGNOSIS: Precise diagnosis of dissection of the cervical artery--carotid or vertebral--is possible with cervical axial magnetic resonance imaging and magnetic resonance angiography. TREATMENT: The recommended treatment in the acute phase of cervical artery dissection is anticoagulant or antithrombotic therapy, aimed at preventing a primary or recurrent ischemic event. There have been as yet no results of randomized controlled studies comparing efficacy of both treatments. An ongoing randomized multicentre study is expected to provide answers about the effects of these treatments in cervical artery dissection. OUTCOME: Complete resolution of arterial abnormalities is achieved in around 46% of stenoses. 33% of occlusions, and 12% of dissecting aneurysms. RECURRENT EVENTS: Recurrence of cerebral ischemia and cervical artery dissection seems to be rare, although some data suggest that early ischemic and late cervical artery dissection recurrences could be underestimated. MORTALITY AND FUNCTIONAL OUTCOME: In comparison with other causes of stroke in young adults, the functional outcome of cervical artery dissection is good in contrast to its socio-professional effects, which may be unsatisfactory. The mortality rate of cervical artery dissection is low, although it may be underestimated since some patients with malignant infarction die before the diagnosis is established. CONCLUSION: Further research is warranted to improve our understanding of the underlying pathophysiology, to assess the long-term outcome, and ultimately to provide treatment and prevention strategies.

Does massive cerebral venous thrombosis mean poor outcome?

A 21-year-old woman taking oral contraceptives presented with headaches, nausea, vomiting and somnolence. The next day she had a generalized tonic-clonic seizure after which her neurological condition deteriorated. CT and MRI showed multiple cerebral haemorrhages, while MR venography revealed extensive dural sinus and venous thrombosis involving almost all sinuses, great cerebral vein of Galen and internal cerebral veins. Two weeks after initiation of the anticoagulant treatment the patient recovered completely with complete recanalization of all cerebral sinuses and veins. Although the patient had conditions which were indicative of poor outcome, her neurological deficit improved completely, which correlated with recanalization of the thrombosed vessels.

Our experience with thrombolytic therapy -- preliminary report.

Stroke is a rapidly developing clinical disturbance of focal or global cerebral function, lasting for more than 1 hour. It is an acute form of symptoms of brain function disorder, with no apparent cause other than vascular origin. It is the final phase of arterial disease, the main cause of disability, and the second leading cause of death. Today, ischemic stroke can be treated successfully by acting on its cause using a very powerful weapon, thrombolytic therapy. The aim is to present a preliminary report of our experiences with thrombolytic therapy in patients with ischemic stroke. Results recorded in 20 patients who received thrombolytic therapy within three hours of stroke onset are presented. Nineteen patients survived and one patient died from therapy side effects, i.e. intracerebral hematoma. Seventeen of 19 patients were released from the hospital without any neurologic deficit, while two patients had Rankin score 2 (minimum disability) three months after stroke onset. Our experience confirms that thrombolytic therapy is the treatment of choice in patients with ischemic stroke if administered in accordance with precise protocols.

Functional outcome after thrombolytic therapy.

In this paper, we report our experience from a prospective study in 40 ischemic stroke patients admitted during the last two years at University Department of Neurology Stroke Unit, Banja Luka Clinical Center, in order to assess the safety and efficacy of thrombolytic therapy, the impact of age, sex and risk factors, and functional outcome at 6 months of intravenous tissue plasminogen activator treatment. According to the National Institutes of Health Stroke Scale, there were 5 mild, 22 moderate and 13 severe stroke cases in the study group. The outcome measures at 6 months of thrombolytic treatment were taken in 38 (100%) patients, yielding a Functional Independent Measure score > or=90 (good clinical outcome) in 21 (52.50%) and modified Rankin Score < or =2 (good clinical outcome) in 22 (55%) patients. The rate of symptomatic intracerebral hemorrhage in tissue plasminogen activator treated patients was 5%, with a mortality rate of 17.50%. The outcomes were comparable with those found in the NINDS t-PA trial. Current guidelines recommend a 'door-to-needle' time of less than 60 minutes and emphasize that 'time is brain'.

Paradoxical emboli--clinical importance of transcranial Doppler for detection of patent foramen ovale.

A patent foramen ovale has been reported to be more frequently detected in cryptogenic stroke, with paradoxical embolism as the major pathogenetic mechanism. The standard procedure for the detection of a patent foramen ovale is transesophageal echocardiography. Transcranial Doppler sonography with bubble test is almost as reliable as transesophageal echocardiography. Seventeen patients with acute ischemic stroke and transient ischemic attacks hospitalized at the Department of Neurology in Novi Sad underwent examinations to detect a patent foramen ovale, which was found in 55.6% of patients with cryptogenic stroke. The average age of these patients was 30.6 years. Transcranial Doppler sonography showed 100% sensitivity and 100% specificity for the prediction of right-to-left shunts proven by transesophageal contrast echocardiography. Both positive and negative predictive values in our group of patients were 1. Transcranial Doppler with bubble test is a reliable method for the detection of a patent foramen ovale, with a high level of sensitivity and specificity which is comparable with transesophageal echocardiography. Moreover, it is cheaper and more comfortable than transesophageal echocardiography, and should be used routinely in neurological practice.

Effects of relapsing-remitting multiple sclerosis treatment with interferon beta-1b results of a three-year follow-up study.

The aim of this prospective study was to evaluate therapeutic effects in a cohort of 32 patients with relapsing-remitting multiple sclerosis (RRMS) that were continuously treated with interferon beta-1b during a three-year period and to compare the results obtained with literature data available. Additionally, dropouts and side effects were assessed. The annual relapse rate at three years of treatment as the primary study end-point decreased by 60.5% compared with the relapse rate throughout the pretherapeutic course of disease (0.39 +/- 0.55 vs. 0.97 +/- 0.46; P<0.001) and by 71.3% compared with the relapse rate one year prior to treatment (0.39 +/- 0.55 vs. 1.34 +/- 0.65; P<0.001). The mean Extended Disability Status Scale (EDSS) increased significantly from 2.46 +/- 0.86 at baseline to 2.90 +/- 1.30 (P<0.01) at three years of treatment, whereas the mean progression index (EDSS/disease duration) decreased significantly from 0.76 +/- 0.50 prior to treatment to 0.43 +/- 0.24 (P<0.001), yielding a 56.6% improvement and proving the disease modifying effect of interferon beta-1b. Seventeen (53.12%) patients remained relapse-free during the course of therapy. Among patients that experienced disease relapse, the mean time to first exacerbation was 11.5 +/- 8.34 months. Our study results were consistent with similar studies performed worldwide, clearly indicating that Interferon beta-1b therapy decreased the disease activity and had a beneficial effect on the progression of RRMS, with low incidence and severity of serious side effects. This study has paved way for further long-term follow up studies at our institution.