Effect of Subthalamic Nucleus Stimulation on Pedunculopontine Nucleus Neural Activity.

BACKGROUND: The pedunculopontine nucleus has recently been proposed as an alternative target for deep brain stimulation for the treatment of medically intractable Parkinson's disease. The suggested indication for pedunculopontine nucleus deep brain stimulation is severe and medically intractable axial symptoms such as gait and postural impairment. OBJECTIVE: Our goal in this study was to describe the effects of subthalamic nucleus stimulation on pedunculopontine nucleus electrophysiological activity. METHODS: Fourteen male Wistar rats were divided into a sham stimulation group and an experimental group. In both groups, electrodes were implanted bilaterally into the subthalamic nucleus and into the right pedunculopontine nucleus. Microelectrode recordings were carried out in both groups prior to and during subthalamic nucleus stimulation. RESULTS: Subthalamic nucleus stimulation produced no clear inhibition of neuronal firing in the pedunculopontine nucleus. However, we found that stimulation of the subthalamic nucleus at 60 Hz produces some entrainment of pedunculopontine nucleus neuronal firing and a shift of subthalamic nucleus firing patterns to more tonic and random patterns. These results are consistent with the effects of deep brain stimulation on neuronal activity in the subthalamic nucleus and globus pallidus internus. CONCLUSION: The result of this study provides additional evidence to improve our understanding of the mechanism of subthalamic nucleus-deep brain stimulation, and its physiological consequences.

Increased Expression of Matrix Metalloproteinase-9 in Patients with Temporal Lobe Epilepsy.

AIM: The molecular mechanism of epileptogenesis in temporal lobe epilepsy is still unclear. Experimental studies have suggested that matrix metalloproteinases have important roles in this process, but human studies are limited. The aim of this study was to assess the expression of MMP-9, MMP-2 and their tissue inhibitors (TIMP-1 and TIMP-2) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). MATERIAL AND METHODS: The tissue samples from temporal neocortex and hippocampus were obtained from patients with temporal lobe epilepsy with hippocampal sclerosis who had undergone anterior temporal lobectomy for recurrent medically resistant seizures. Immunohistochemical methods were used to determine the expression of MMP-9, MMP-2 and their tissue inhibitors. Tissue samples were also analyzed with transmission electron microscopy. RESULTS: The immunoreactivity for MMP-9 both in hippocampal and temporal neocortical neurons was stronger than that of MMP-2. Additionally, there was a mild reaction for its tissue inhibitor TIMP-1 as with TIMP-2. The TEM analysis of the hippocampus revealed that there was apparent ultra-structural damage on the pericarya and neuropil of some neurons. There was obvious damage in the mitochondria and the nuclear membrane. CONCLUSION: The preliminary results of this study revealed that MMP-9 may have a role in patients with drug resistant TLE-HS.

The effects of brain stimulation of subthalamic nucleus surgery on gait and balance performance in Parkinson disease. A pilot study.

INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by tremor, rigidity and bradykinesia. Gait and postural difficulties supersede tremor, rigidity and bradykinesia as drivers of disease burden in patients with advanced PD. The aim of this study was to describe the effects of deep brain stimulation of the subthalamic nucleus on gait ability and balance performance in patients with PD. MATERIAL AND METHODS: We studied 19 consecutive patients who underwent bilateral stimulation of the subthalamic nucleus. Patients were evaluated preoperatively and at the 5(th) day and 6(th) month after surgery. Timed Up and Go Test, 12 m Walking Test, Chair Stand Test and Berg Balance Scale (BBS) were used to assess mobility and balance performance. Unified Parkinson's Disease Rating Scale (UPDRS III) and Hoehn and Yahr Scale were also used. RESULTS: All the patients' mobility ability and balance performance improved after surgery (p < 0.05). At the 6th month after surgery, the Timed Up and Go Test scores were decreased from 56.05 ±42.52 to 21.47 ±20.36, the 12 m Walking Test scores were decreased from 100.44 ±66.44 to 28.84 ±19.79, the Chair Stand Test scores were increased from 4.00 ±4.66 to 11.68 ±4.43 and the BBS score was increased from 12.84 ±6.89 to 38.89 ±8.79. UPDRS total scores were significantly improved 6 months after surgery (p < 0.001). UPDRS total scores were decreased from 98.26 ±37.69 to 39.36 ±18.85. The Hoehn and Yahr Scale score was significantly decreased after surgery (p < 0.05). CONCLUSIONS: Surgical therapy is an effective treatment to improve gait ability and balance performance in Parkinson's patients.

Reuse of internal pulse generator in cases of infection after deep brain stimulation surgery.

BACKGROUND: Hardware-related infection after deep brain stimulation (DBS) is one of the most serious complications and may need additional interventions. OBJECTIVES: To reuse the internal pulse generator (IPG) after DBS infection and to reduce the economic costs. METHODS: A database of 102 patients who underwent DBS surgery was used in the study. The incidence, clinical characteristics and management of infections while reusing the IPG after DBS-related infection were analyzed and reported. RESULTS: The overall infection rate was 5.9% (6 of 102 patients). Management consisted of total hardware removal followed by intravenous antibiotics. The IPG was at first kept in a solution, then rinsed with water and dried following sterilization with ethylene oxide gas at 38 °C for 18 h. When the treatment of the infection was finished, we reused the IPG and reimplanted the DBS. No hardware-related infection or other complications were observed after reimplantation. CONCLUSIONS: Management of hardware-related infections can be challenging. The medical and economic costs associated with these infections are enormous. The IPG can often be saved in infected patients. Thus, a significant cost burden is eliminated. Properly executed, reuse of IPG should markedly reduce the costs of these devices.

Manic episode following deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a case report.

AIM: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy for patients with Parkinson's disease (PD) associated with motor complications of long term L-dopa treatment. MATERIAL AND METHODS: Here we report two cases with DBS- induced manic episode, focusing on the functional and anatomic correlates of psychiatric adverse effects of STN stimulation. RESULTS: We present two cases of PD with motor complications due to long term L-dopa treatment that developed their first episodes of mania with psychotic symptoms after bilateral STN-DBS implantation. DBS-induced psychiatric adverse effects may be attributable either to limbic connections and STN-specific oscillations or stimulation of the medial forebrain bundle.

Angiogenesis in neurological disorders: a review.

Angiogenesis, recruitment of new blood vessels, is an essential component of the metastatic pathway. These vessels provide the principal route by which tumor cells exit the primary tumor site and enter the circulation. For many tumors, the vascular density can provide a prognostic indicator of metastatic potential, with the highly vascular primary tumors having a higher incidence of metastasis than poorly vascular tumors. The discovery and characterization of tumor-derived angiogenesis modulators greatly contributed to our understanding of how tumors regulate angiogenesis. However, although angiogenesis appears to be a rate-limiting event in tumor growth and metastatic dissemination, a direct connection between the induction of angiogenesis and the progression to tumor malignancy is less well understood. In this review, we discuss the observations concerning the modulation of angiogenesis and their implications in various neurological disorders, as well as their potential impact on cancer therapy.

A case report of surgically treated drug resistant epilepsy associated with subependymal nodular heterotopia.

Subependymal nodular heterotopia (SNH) is a cortical development malformation that is commonly associated with medically resistant epilepsy. Cases of SNH are challenging to treat surgically because there are typically multiple nodules, which may be involved in epileptogenesis. Moreover, dual pathology may exist in these patients. Here, we present a case with unilateral subependymal heterotopic nodules associated with ipsilateral hippocampal atrophy. Invasive and non-invasive work-ups revealed that the hippocampus was the actual ictal onset zone and that the SNH was not involved. An anterior temporal lobectomy was carried out, and postoperative seizure outcome was class Ia at the end of 2 years. The case demonstrates that SNH may not play a major role in patients with dual pathology. However, direct electroencephalography (EEG) recording from areas of SNH and other possible epileptogenic regions is indispensable in defining the ictal onset zone and avoiding poor surgical outcomes.

The influence of subthalamic nucleus deep brain stimulation on physical, emotional, cognitive functions and daily living activities in patients with Parkinson's disease.

AIM: To describe effectiveness of deep brain stimulation of subthalamic nucleus (DBS STN) on physical, emotional, cognitive functions and daily activities in Parkinson's patients. MATERIAL AND METHODS: Ten patients (51.20 ±10.20 yr.) were assessed three times. The Time Up and Go Test, 12 m Walking Test and Chair Stand Test were used to assess mobility and balance. Purdeu Pegboard and hand writing tests were used to evaluate hand function. The Hospital Anxiety and Depression Scale (HAD) was used to detect depressive symptoms and anxiety score. The Unified Parkinson\'s Disease Rating Scale (UPDRS) and Hoehn &Yahr Scale were also used. The Schwab and England Test was used to evaluate the daily activities (ADL). RESULTS: The results showed that all the patients' mobility and balance ability improved after surgery (p < 0.05). Depressive symptoms / anxiety scores were found to be lower than before surgery (p < 0.05). There were differences in terms of ADL and UPDRS scores after surgery (p < 0.05). At six month after surgery; depressive symptoms decreased by 78%. ADL and UPDRS motor and total scores improved by 190%, 72%, and 78% respectively. CONCLUSION: STN DBS is an effective treatment to improve physical functioning, emotional status and daily activities in Parkinson's patients. However, it did not show any positive effect on cognitive function.

Deep brain stimulation of the pedunculopontine nucleus in a patient with freezing of gait.

CASE PRESENTATION: A 54-year-old male patient presenting probable multiple system atrophy with predominant parkinsonism who underwent bilateral deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is presented. The patient had dominant freezing of gait (FOG), levodopa-resistant bradykinesia, and autonomic disturbances, but with a good cognitive condition. METHODS: The patient underwent bilateral DBS of the PPN, which ended with modest benefits. RESULTS AND CONCLUSION: Although he had a short postoperative follow-up (6 months), his neurological status remained stable and PPN DBS provided modest improvements in the gait disorder and freezing episodes. This unusual case suggests that the mesencephalic pedunculopontine region may have a role in locomotor symptoms and the potential to provide a limited improvement in FOG.

Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats.

AIM: Experimental and clinical studies have revealed that hippocampal DBS can control epileptic activity, but the mechanism of action is obscure and optimal stimulation parameters are not clearly defined. The aim was to evaluate the effects of high frequency hippocampal stimulation on cortical epileptic activity in penicillin-induced epilepsy model. MATERIAL AND METHODS: Twenty-five Sprague-Dawley rats were implanted DBS electrodes. In group-1 (n=10) hippocampal DBS was off and in the group-2 (n=10) hippocampal DBS was on (185 Hz, 0.5V, 1V, 2V, and 5V for 60 sec) following penicillin G injection intracortically. In the control group hippocampal DBS was on following 8 µl saline injection intracortically. EEG recordings were obtained before and 15 minutes following penicillin-G injection, and at 10th minutes following each stimulus for analysis in terms of frequency, amplitude, and power spectrum. RESULTS: High frequency hippocampal DBS suppressed the acute penicillin-induced cortical epileptic activity independent from stimulus intensity. In the control group, hippocampal stimulation alone lead only to diffuse slowing of cerebral bioelectrical activity at 5V stimulation. CONCLUSION: Our results revealed that continuous high frequency stimulation of the hippocampus suppressed acute cortical epileptic activity effectively without causing secondary epileptic discharges. These results are important in terms of defining the optimal parameters of hippocampal DBS in patients with epilepsy.

Vim stimulation in Holmes' tremor secondary to subarachnoid hemorrhage.

OBJECTIVE AND IMPORTANCE: Vim stimulation is effective in Parkinsonian and essential tremor. Our aim is to prove that it is also effective in other complex tremor syndromes such as Holmes' tremor. CLINICAL PRESENTATION: A 31-year-old previously healthy man developed resting, action, and postural tremor in bilateral upper extremities and orolingual region, which was suggestive of Holmes' tremor, occurring 25 days after a subarachnoid hemorrhage. The initial pharmacotherapy was unsuccessful, including levodopa, bromocriptine, and levetiracetam. INTERVENTION: Bilateral Vim stimulation suppressed both extremity and orolingual tremors which interfered with daily living activities such as eating and swallowing. CONCLUSION: Thalamic Vim stimulation seems to be a good treatment option in medically intractable complex tremor syndromes.

Demographic and historical backgrounds of the elderly with nonepileptic seizures: a comparative study.

BACKGROUND: Non-epileptic seizures (NES) are not infrequent in the elderly. However, the data on NES in the elderly is likited. AIM: To study the demographic and historical background of eldely patients with NES and compare the same with the data in the younger patients with NES. MATERIALS AND METHODS: Patients with NES over 55 years of age and the next two consecutive patients with NES between ages 18 and 45 were compared in terms of demographic and historical features, psychiatric evaluation and MMPI testing. RESULTS: Of all the 128 patients with NES, 13 (10.6%) were over 55 years of age. History of physical/sexual abuse was high in both the groups. The mean length of time for NES diagnosis was longer in the elderly (13.38 +/- 15.33 vs. 6.15 +/- 8.04 years; P < 0.05). Majority of the patients with NES were on AEDs without evidence of epilepsy and almost half in both the groups were using benzodiazepines. CONCLUSION: In demographic and historical aspects old and young patients do not display major differences; however, the diagnosis is significantly delayed in the elderly. Early diagnosis with video EEG is recommended to avoid potential long-term risks associated with inappropriate treatments.

Influence of Tribulus terrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet.

The aim of this study was to investigate the pleotropic effects of an extract of a traditional herb, Tribulus terrestris (TT), on the lipid profile and vascular endothelium of the abdominal aorta in New Zealand rabbits fed a cholesterol-rich diet. Eighteen rabbits were randomly divided into three groups (n=6 for each). One experimental group (EG-I) was given a cholesterol-rich diet, a second experimental group (EG-II) was treated with TT following a cholesterol-rich diet, and a control group (CG) was fed a standard diet. Blood samples were collected on day 0 and then at weeks 4 and 12 to determine total serum cholesterol (TC), high density lipid-cholesterol (HDL-C), low density lipid-cholesterol (LDL-C) and triglyceride (TG) levels. Tissues were collected from the abdominal aorta for immunohistochemistry and transmission and scanning electron microscopy. In EG-II, the serum lipid profile was significantly lower than that of EG-I at week 12 with a reduction of TC: 65%; LDL-C: 66%; HDL-C: 64%; TG: 55%. Ultrastructural analysis revealed that endothelial damage was more prominent in EG-I compared to EG-II. The ruptured endothelial linings and damaged cellular surfaces increased in EG-I compared to EG-II. Our data indicate that dietary intake of TT can significantly lower serum lipid profiles, decrease endothelial cellular surface damage and rupture and may partially repair the endothelial dysfunction resulting from hyperlipidemia.

Seizure outcome following transcortical selective amygdalohippocampectomy in mesial temporal lobe epilepsy.

The aim of this study was to retrospectively determine if patients with medically refractory epilepsy, due to hippocampal sclerosis, who underwent selective amygdalohippocampectomy (SAH) with a transcortical approach experienced improved seizure outcome. Thirty-nine patients with mesial temporal lobe epilepsy and hippocampal sclerosis were included in the study. The mean follow-up was 25.88 +/- 17.69 months. Antiepileptic medication use and seizure frequency were significantly reduced after SAH. After surgery, 32 patients (82.05%) were completely seizure free (Engel class IA), and 2 patients experienced transient memory difficulty. In conclusion, SAH with a transcortical approach can lead to favorable seizure control with a low irreversible complication risk.

Effects of excess vitamin B6 intake on cerebral cortex neurons in rat: an ultrastructural study.

The aim of this study was to investigate whether excess of vitamin B6 leads to ultrastructural changes in cerebral cortex of forty-eight healthy albino rats which were included in the study. Saline solution was injected to to the control groups (CG-10, n = 12 for 10 days; CG-15, n = 12 for 15 days; CG-20, n=12 for 20 days). The three experimental groups (EG-10, n = 12; EG-15, n = 12; EG-20, n = 12) were treated with 5 mg/kg vitamin B6 daily for 10 days (EG-10), 15 days (EG-15) and 20 days (EG-20). Brain tissues were prepared by glutaraldehyde-osmium tetroxide double fixation for ultrastructural analysis. No significant changes were observed in the control groups. The ultrastructural analysis revealed that the numbers of damaged mitochondria, lipofuscin granules and vacuoles were significantly higher in all the experimental groups than in the control groups (p < 0.05). However, synaptic density was significantly decreased in the experimental groups as compared to the control groups (p < 0.05). The results suggest that the excess of vitamin B6 intake causes damage to the cerebral cortex due to cellular intoxication and decreased synaptic density. Thus, careful attention should be paid to the time and dose of vitamin B6 recommended for patients who are supplemented with this vitamin.

Resolution of neurogenic arterial hypertension after suboccipital decompression for Chiari malformation. Case report.

A Chiari malformation Type I may remain asymptomatic until the patient has reached adulthood and acute presentation of symptoms occurs. In several clinical and experimental studies it has been shown that essential hypertension is associated with vascular compression of the brainstem, particularly of the rostral ventrolateral medulla oblongata. Nevertheless, two cases of Chiari malformation and neurogenic arterial hypertension have been reported. In this article the authors describe a patient with Chiari malformation Type I and neurogenic arterial hypertension. A simple suboccipital decompression not only provided neurological improvement, but also led to resolution of the hypertension. In cases of Chiari malformation and concomitant neurogenic arterial hypertension, careful preoperative clinical and neuroimaging assessments may reveal the cause of the arterial hypertension. Resolution of neurogenic arterial hypertension may be expected even in a case of simple suboccipital decompression.

Intrathecal sICAM-1 production in multiple sclerosis--correlation with triple dose Gd-DTPA MRI enhancement and IgG index.

In this study the aim was to evaluate the intrathecal sICAM-1 production in multiple sclerosis (MS) patients during relapse and remission. In addition to this, we assessed whether there is a correlation between intrathecal sICAM-1 production and other disease activity markers such as IgG index and gadolinium enhancement in magnetic resonance imaging (MRI). Twenty four relapsing-remitting MS patients were included in the study. Serum and cerebrospinal fluid (CSF) samples were obtained both during relapse and remission. The soluble form of ICAM (sICAM) was measured by the ELISA method in serum and CSF. Cranial MRI with triple dose gadolinium injection was performed for each patient both during relapse and remission. Serum levels of sICAM-1 (245.23 +/- 92.88 ng/ml) were higher during relapse than those in remission (219.90 +/- 110.94 ng/ml), but the difference was not statistically significant. In relapse periods CSF levels of sICAM-1 (1.304 +/- 0.92 ng/ml) were higher than those in remission (1.06 +/- 0.86 ng/ml), but this was not significant. However, during relapse periods patients had significantly higher sICAM-1 index values (1.76 +/- 0.60) than those found during remission periods (1.01 +/- 0.44) (p < 0.05). The IgG index values were higher in relapse periods than in remission (0.88 +/- 0.37 vs. 0.67 +/- 0.28) (p < 0.005). On T1 weighted images following triple dose Gd injection, at least two or more enhancing lesions were present in 22/24 of the patients (91%) in relapse and 4/24 of the patients (19%) in remission. There was strong correlation both between the sICAM-1 index and Gd enhancement (r =0 .72 p < 0.05) and sICAM-1 index and IgG index in relapse (r = 0.69 p < 0.05). In conclusion, there is association between high sICAM-1 and IgG indices, as well as between high sICAM-1 index and Gd enhancing MRI lesions in relapsing MS patients.

Ultrastructural and immunohistochemical similarities of two distinct entities; multiple sclerosis and hereditary motor sensory neuropathy.

In the present study, we present the ultrastructural and immunohistochemical properties of the sural nerves of two patients, one of whom was diagnosed as having multiple sclerosis with involvement of the peripheral nervous system (PNS), and the other as having hereditary motor sensory neuropathy type-I with involvement of the central nervous system (CNS). Expression of several extracellular matrix (ECM) proteins (fibronectin, laminin, and collagen type-IV), intermediate filaments (vimentin) and S-100 protein (marker for the axon-Schwann cell interface) was investigated by means of immunohistochemical methods. In addition, the tissue samples were evaluated ultrastructurally. Immunohistochemical staining revealed increased expression of the ECM molecules mentioned above in relation with the sural nerves of the patients. We hypothesize that this enhanced expression is due to Schwann cell-axon interactions. Vimentin expression was different in Schwann cells and S-100 immunostaining was decreased near the Schwann cell-axon interface. Myelin fragmentation, axon vacuolization, onion bulbs, tomoculous formation, axonal degeneration were found to occur. These results suggest that there is active ECM reorganization in the sural nerve of these patients, and some ultrastructural changes are similar in the damaged axonal organization and in Schwann cells although the changes are not completely the same in the two patients. In conclusion, our study demonstrates that there is an association between the demyelinization process in the CNS and the PNS even though they are affected by different mechanisms.

Visual evoked potential is superior to triple dose magnetic resonance imaging in the diagnosis of optic nerve involvement.

The aim of this study was to evaluate whether VEP is sensitive to optic neuritis (ON) when compared with triple dose orbital MRI. Twenty-four relapsing-remitting MS (RRMS) patients were included in the study. Group I (n = 10) patients with acute ON, Group II (n = 8): patients presenting with a current relapse who had the history of ON in the previous relapses. Group III (n = 6): patients presenting with a current relapse but with no history of ON. Neuro-ophtalmological evaluation. VEP investigation and orbital MRI with triple dose (0.3 mmol/kg) gadolinium (Gd) were carried out for all. VEP was found to be 70% sensitive and 12.5% specific to the acute ON, whereas orbital MRI with triple dose Gd was 70% sensitive and 100% specific. In chronic ON, the sensitivity of orbital MRI is 0%, whereas the VEP is still 75% sensitive to chronic optic nerve involvement and can distinguish the pathology 100% specifically. In conclusion, orbital MRI with triple dose Gd is not more sensitive than VEP in determining the acute optic nerve pathologies but it is a 100% specific method. The results suggest that VEP is superior to the orbital MRI in determining the chronic optic nerve involvement.