Hakan Ekmekci

A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study

BACKGROUND Based on a number of small observational studies, cerebral venous sinus thrombosis has diverse clinical and imaging features, risk factors, and variable outcome. In a large, multicenter cerebral venous thrombosis (VENOST) study, we sought to more precisely characterize the clinical characteristics of Caucasian patients. METHODS All data for the VENOST study were collected between the years 2000 and 2015 from the clinical follow-up files. Clinical and radiological characteristics, risk factors, and outcomes were compared in terms of age and sex distribution. RESULTS Among 1144 patients 68% were women, and in older age group (>50 years) male patients were more prevalent (16.6% versus 27.8%). The most frequent symptoms were headache (89.4%) and visual field defects (28.9%) in men, and headache (86.1%) and epileptic seizures (26.8%) in women. Gynecological factors comprised the largest group in women, in particular puerperium (18.3%). Prothrombotic conditions (26.4%), mainly methylenetetrahydrofolate reductase mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders. 8.1% of patients had infection-associated and 5.2% had malignancy-related etiology that was significantly higher in men and older age group. Parenchymal involvement constitutively hemorrhagic infarcts, malignancy, and older age was associated with higher Rankin score. Epileptic seizures had no effect on prognosis. CONCLUSIONS Clinical and radiological findings were consistent with previous larger studies but predisposing factors were different with a higher incidence of puerperium. Oral contraceptive use was not a prevalent risk factor in our cohort. Malignancy, older age, and hemorrhagic infarcts had worse outcome.

Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia

Background: Camptocormia is known as “bent spine syndrome” and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinsons disease (PD). Case Description: We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. Conclusion: The relationship between the DBS and camptocormia is discussed in this unique condition.

Clinical and Radiological Features in CADASIL and NOTCH3-Negative Patients: A Multicenter Study from Turkey

Background: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. Methods: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. Results: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). Conclusion: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

A database for screening and registering late onset Pompe disease in Turkey

The aim of this study was to search for the frequency of late onset Pompe disease (LOPD) among patients who had a myopathy with unknown diagnosis registered in the pre-diagnostic part of a novel registry for LOPD within a collaborative study of neurologists working throughout Turkey. Included in the study were 350 patients older than 18 years who have a myopathic syndrome without a proven diagnosis by serum creatine kinase (CK) levels, electrodiagnostic studies, and/or muscle pathology, and/or genetic tests for myopathies other than LOPD. Acid alpha glucosidase (GAA) in dried blood spot was measured in each patient at two different university laboratories. LOPD was confirmed by mutation analysis in patients with decreased GAA levels from either both or one of the laboratories. Pre-diagnostic data, recorded by 45 investigators from 32 centers on 350 patients revealed low GAA levels in a total of 21 patients; from both laboratories in 6 and from either one of the laboratories in 15. Among them, genetic testing proved LOPD in 3 of 6 patients and 1 of 15 patients with decreased GAA levels from both or one of the laboratories respectively. Registry was transferred to Turkish Neurological Association after completion of the study for possible future use and development. Our collaborative study enabled collection of a considerable amount of data on the registry in a short time. GAA levels by dried blood spot even from two different laboratories in the same patient may not prove LOPD. LOPD seemed to be rarer in Turkey than in Europe.

Effect Transformation of the Micro Electrode Recording (MER) Data to Fast Fourier Transform (FFT) for the Main Target Nucleus Determination for STN-DBS

Introduction: Advanced PD stimulation of the STN reduces tremor, rigidity, and bradykinesia. Due to hemorrhagic complications the use of micro electrode recordings during DBS operation was still questioning for some of surgeons. But use micro electrodes were still the best choice for the positioning during surgery of DBS. Aim: The aim of the current study was to investigate the effect transformation of the micro electrode recording data to fast fourier transform for the main target nucleus determination. This process needs a multidisciplinary approach from neurosurgery, neurology and specialists on electrophysiology such as biophysics. Case report: We present the case of a 63 year-old male with medically intractable PD is focused on behalf of the surgical treatment. Patient had a 4-year history of progressively severe hand tremor on right side. The patient was successfully treated unilaterally with the STN DBS.

Behçet’s disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study

OBJECTIVE This study was performed to determine the rate of cerebral venous sinus thrombosis (CVST) among cases of Behçets disease (BD) included in a multicentre study of cerebral venous sinus thrombosis (VENOST). METHODS VENOST was a retrospective and prospective national multicentre observational study that included 1144 patients with CVST. The patients were classified according to aetiologic factors, time of CVST symptom onset, sinus involvement, treatment approach and prognosis. RESULTS BD was shown to be a causative factor of CVST in 108 (9.4%) of 1144 patients. The mean age of patients in the BD group was 35.27 years and 68.5% were men, whereas in the non-BD CVST group, the mean age was 40.57 years and 28.3% were men (P < 0.001). Among the aetiologic factors for patients aged 18-36 years, BD was predominant for men, and puerperium was predominant for women. The onset of symptoms in the BD group was consistent with the subacute form. The transverse sinuses were the most common sites of thrombosis, followed by the superior sagittal sinuses. The most common symptom was headache (96.2%), followed by visual field defects (38%). CONCLUSIONS BD was found in 9.4% of patients in our VENOST series. Patients with BD were younger and showed a male predominance. The functional outcome of CVST in patients with BD was good; only 12% of patients presenting with cranial nerve involvement and altered consciousness at the beginning had a poor outcome (modified Rankin Score ⩾2).

Elevated Urinary Methylmalonic Acid/creatinine ratio and Serum Sterol levels in Patients with Acute Ischemic Stroke

Abstract Introduction: Sitosterolemia, defined as phytosterolemia, is a rare autosomal recessive disease characterized by elevated blood sterol levels. Our aim was to investigate serum plant sterols, methylmalonic acid, vitamin B12, oxidized-LDL and homocysteine levels in ischemic and hemorrhagic stroke patients and healthy subjects. Material and Methods: 50 healthy subjects (without a family history of coronary artery disease) and 89 patients hospitalized in the Selcuk University neurology clinic or intensive care unit with a diagnosis of stroke were included in this study. Serum plant sterols, homocysteine and methylmalonic acid, oxidized-LDL, total cholesterol, triglycerides, HDL-Cholesterol and vitamin B12 levels were analyzed by gas chromatography-mass spectrometry, liquid-chromatography tandem mass spectrometry, commercially available ELISA kit, spectrophotometry and chemiluminescence methods, respectively. Results: Urinary methylmalonic acid/creatinine ratio (p< 0.05), serum β-sitosterol levels and β-sitosterol/ cholesterol ratio were significantly higher (p <0.01) in patients compared to the control group. There was a significant positive correlation between the serum OxLDL- methylmalonic acid, serum homocysteine- urinary methylmalonic acid /creatinine ratio, serum methylmalonic acid - Urinary methylmalonic acid (p<0.05), serum homocysteine- urinary methylmalonic acid, urinary methylmalonic acid-methylmalonic acid/creatinine ratio, serum methylmalonic acid- methylmalonic acid/creatinine ratio, serum beta-sitosterol- beta-sitosterol /cholesterol, total cholesterol-HDL, total cholesterol-LDL (p <0.01) levels and negative correlation between vitamin B12- serum methylmalonic acid (p<0.05), cholesterol-stigmasterol/cholesterol, LDL- stigmasterol/cholesterol (p <0.01) levels in the patient group. Conclusion: Our findings presented that the serum sitosterol levels were significantly higher in stroke patients compared to controls.

“Long-term Results for Single Electrode-Guided Deep Brain Stimulation Used to Treat Parkinson’s Disease

Introduction The optimal method for targeting the subthalamic nucleus (STN) and positioning the deep brain stimulation (DBS) electrode is still controversial. In this study, single channel-guided stimulations were used in order to determine the most proper way to target the STN. Findings were synthesised for use in clinical situations. This paper presents the long-term results of DBS applied using single-channel guidance. Methods We retrospectively reviewed 15 patients who had undergone STN-DBS to treat Parkinsons disease in-between 2010 and 2017. All patients were examined preoperatively, and they were routinely followed-up 2-7 years postoperatively. Results The use of single-channel guidance resulted in better outcomes of motor complaints of Parkinsons patients. Moreover, a significantly greater improvement in Unified Parkinsons Disease Rating Scale Score (UPDRS) was achieved in either ON or OFF periods of patients. Conclusion Single channel-guided STN-DBS is a safe procedure and it results in improved motor outcomes in advanced Parkinsons Disease.

Vagal Nerve Stimulation

BACKGROUND: The vagus nerve stimulation (VNS) is an approach mainly used in cases of intractable epilepsy despite all the efforts. Also, its benefits have been shown in severe cases of depression resistant to typical treatment. AIM: The aim of this study was to present current knowledge of vagus nerve stimulation. MATERIAL AND METHODS: A new value has emerged just at this stage: VNS aiming the ideal treatment with new hopes. It is based on the placement of a programmable generator on the chest wall. Electric signals from the generator are transmitted to the left vagus nerve through the connection cable. Control on the cerebral bioelectrical activity can be achieved by way of these signal sent from there in an effort for controlling the epileptic discharges. RESULTS: The rate of satisfactory and permanent treatment in epilepsy with monotherapy is around 50%. This rate will increase by one-quarters (25%) with polytherapy. However, there is a patient group roughly constituting one-thirds of this population, and this group remains unresponsive or refractory to all the therapies and combined regimes. The more the number of drugs used, the more chaos and side effects are observed. The anti-epileptic drugs (AEDs) used will have side effects on both the brain and the systemic organs. Cerebral resection surgery can be required in some patients. The most commonly encountered epilepsy type is the partial one, and the possibility of benefiting from invasive procedures is limited in most patients of this type. Selective amygdala-hippocampus surgery is a rising value in complex partial seizures. Therefore, as epilepsy surgery can be performed in very limited numbers and rather developed centres, success can also be achieved in limited numbers of patients. The common ground for all the surgical procedures is the target of preservation of memory, learning, speaking, temper and executive functions as well as obtaining a good control on seizures. However, the action mechanism of VNS is still not exactly known. On the other hand, it appears to be a reliable method that is tolerated well in partial resistant seizures. It has been observed that adverse effects are generally of mild-medium severity, and most of the problems can be eliminated easily through the re-adjustment of the stimulator. CONCLUSION: VNS, which is a treatment modality that will take place it deserves in epilepsy treatment with “the correct patient” and “correct reason”, must be known better and its applications must be developed.

Language Disorders due to Posterior System Strokes - An Ignored Dysfunction

The anterior system is primarily responsible for the clinical picture in a patient that presents with clinical aphasia. However, recent reports have shown that injuries to posterior structures, the cerebellum in particular, may have a role in language processing. Herein, we will look first at the linguistic role of the cerebellum in light of the literature, then of the thalamus and some described clinical syndromes, and finally, specific syndromes resulting from occipital lobe lesions, all of which are supported by the posterior vascular system. The human brain is such a complex organization that in addition to the thalamus and occipital cortex, we can see the involvement of the cerebellum in high cognitive functions. Posterior system strokes may lead to clinical findings of cognitive deficits, including neurolinguistic components. Determining these defects in stroke patients may precipitate changes in current management strategies.