Clinical efficacy and safety of anterior thalamic deep brain stimulation for intractable drug resistant epilepsy.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) is a neuromodulation therapy for patients with refractory focal seizures evolving into bilateral tonic-clonic seizures when pharmacotherapy as well other neuromodulation techniques including vagus nerve stimulation or responsive neurostimulation have failed. OBJECTIVE: We performed a prospective single-center study investigating the clinical efficacy and exact ANT DBS lead location in patients with DRE. METHODS: The primary outcome measure was the proportion of patients with more than 50 % reduction in diary-recorded seizures when compared to three preoperative months (baseline seizure frequency). The close postoperative follow-up was performed every 3 months. The seizure frequency, stimulation settings and adverse events were closely monitored during follow-up visits. We also analyzed the seizure outcome with location of ANT DBS active contacts. RESULTS: Between May 2020 and October 2022, 10 adult patients with a mean age of 38.5 years (range, 30-48 years) underwent bilateral ANT DBS surgery (mean duration of DRE 28.6 years, range 16-41 years). The median seizure count in three months period preceding surgery (baseline seizure count) was 43.2 (range, 4-150). Nine patients achieved more than 50 % seizure reduction at the last follow-up (mean range 3-33 13.6 months, months). ANT DBS caused seizure reduction 3 months after procedure as well as at last follow-up by 60.4 % and 73.3 %, respectively. Due to relatively small number of studying individuals we cannot precisely locate the area within ANT associated with good clinical outcome. Patients with temporal lobe epilepsy had a remarkable reduction of seizure frequency. No patient suffered transient or permanent neurological deficits. CONCLUSIONS: Clinical efficacy of ANT DBS may support more widespread utilization of this neuromodulation technique especially for seizures originating from temporal lobes.

Atypical clinical presentation of glioblastoma mimicking autoimmune meningitis in an adult.

Glioblastoma (GBM) is the most malignant type of glial tumor associated with a very unfavorable prognosis. Typical radiological features of GBM include the presence of a tumor with irregular contrast-enhancing margins and central necrosis surrounded by a wide area of vasogenic edema. Here, we presented an atypical clinical presentation of GBM mimicking autoimmune meningitis. A 69-years-old previously healthy male was admitted to the emergency room due to signs of increasing cognitive impairment, weight loss, changes in behavior, difficulty in walking, and prolonged episodes of nausea over the past month. An magnetic resonance imaging (MRI) brain scan revealed hyperintense changes of the periventricular area surrounding brain ventricles in T2 and FLAIR, and post-contrast leptomeningeal enhancement and thickening of meninges involving cerebellar sulci. An additional MRI scan of the cervical spine showed an in-core contrastenhancing lesion on the C7-Th1 level as well as leptomeningeal thickening and post-contrast-enhancement around the spinal cord. Various laboratory tests and two stereotactic biopsies were performed with no essential to diagnosis clinical findings. A couple of months after first hospital admission, the patient died. Post-mortem examination of the brain revealed numerous foci of abnormal tissue inside the subarachnoid space, lateral ventricles, and cerebral aqueduct. Histological examination showed diffuse malignant astroglial neoplasm, and diagnosis of glioblastoma NOS WHO G IV was established. Even though the appearance of usual GBM is widely recognizable, one must bear in mind the possibility of unusual presentation. The presented case highlights the diagnostic difficulties of diffuse glioblastoma with atypical clinical presentation.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer. The results of this study suggested the use of routine determination of PGRN in the clinic as a reliable biomarker for screening people at high risk or as early indication of breast cancer. Targeting PGRN and its associated signaling pathways and receptors, such as sortilin (SORT1), could also cover a novel therapeutic strategy in the breast cancer.

Acute disseminated encephalitis in an adult patient addicted to heroin. Neuropathological, neuroradiological and clinical features.

Acute disseminated encephalomyelitis (ADEM) is an immune demyelinating central nervous system (CNS) disorder, characterized by monophasic new onset neurological symptoms including encephalopathy, combined with neuroradiological evidence of multifocal demyelination. ADEM is extremely rarely diagnosed and is much more common in children and adolescents than in adults. The aim of this study is to present an extremely rare case of ADEM in a heroin-addicted patient with a very difficult diagnostic course. The results of the magnetic resonance imaging (MRI) examination in this patient were inconclusive. Fungal abscesses or inflammatory lesions of an unclear nature were suspected especially in a patient with impaired immunodeficiency. In view of the constantly deteriorating condition of the patient with disturbed consciousness and the unclear aetiology, the lack of effective treatment, a decision was made to perform a bilateral stereotactic biopsy and aspiration of brain abnormalities in order to obtain a neuropathological specimen and begin with the causal treatment. Neuropathological examination revealed the presence of Creutzfeldt-Peters cells characteristic of ADEM. Treatment with methylprednisolone significantly improved the patient's general and neurological condition. To our knowledge, the above case is the first in the world literature in which ADEM has been confirmed by bilateral stereotaxic aspiration for the treatment of symptoms of increased intracranial pressure as a lifesaving procedure. Neuropathological confirmation allowed for the implementation of appropriate treatment, which resulted in complete recovery. Moreover, this case is interesting because ADEM was diagnosed in a patient addicted to heroin, where opportunistic inflammation of a fungal aetiology was considered in the first place.

Systematic and Multidisciplinary Evaluation of Fibromuscular Dysplasia Patients Reveals High Prevalence of Previously Undetected Fibromuscular Dysplasia Lesions and Affects Clinical Decisions: The ARCADIA-POL Study.

Fibromuscular dysplasia (FMD), regarded as a generalized vascular disease, may affect all vascular beds and may result in arterial stenosis, occlusion, aneurysm, or dissection. It has been proposed to systematically evaluate all vascular beds in patients with FMD, regardless of initial FMD involvement. However, the impact of this approach on clinical decisions and on management is unknown. Within the prospective ARCADIA-POL study (Assessment of Renal and Cervical Artery Dysplasia-Poland), we evaluated 232 patients with FMD lesions confirmed in at least one vascular bed, out of 343 patients included in the registry. All patients underwent a detailed clinical evaluation including computed tomography angiography of intracranial and cervical arteries, as well as computed tomography angiography of the abdominal aorta, its branches, and upper and lower extremity arteries. In the study group, FMD lesions were most frequently found in renal arteries (87.5%). FMD was also found in cerebrovascular (24.6%), mesenteric (13.8%), and upper (3.0%) and lower extremity (9.9 %) arteries. Newly diagnosed FMD lesions were found in 34.1% of the patients, and previously undetected vascular complications were found in 25% of the patients. Among all FMD patients included in the study, one out of every 4 evaluated patients qualified for interventional treatment due to newly diagnosed FMD lesions or vascular complications. The ARCADIA-POL study shows for the first time that the systematic and multidisciplinary evaluation of patients with FMD based on a whole-body computed tomography angiography scan has an impact on their clinical management. This proved the necessity of the systematic evaluation of all vascular beds in patients with FMD, regardless of initial FMD involvement.

Increased burden of rare deleterious variants of the KCNQ1 gene in patients with large­vessel ischemic stroke.

The impact of rare and damaging variants in genes associated with platelet function in large­vessel ischemic stroke (LVIS) remains unknown. The aim of this study was to investigate the contribution of some of these variants to the genetic susceptibility to LVIS in Polish patients using a deep re­sequencing of 54 selected genes, coding for proteins associated with altered platelet function. Targeted pooled re­sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of LVIS) and 500 age­, smoking status­, and sex­matched controls (no history of any type of stroke), and from the same population as patients with LVIS. After quality control and prioritization based on allele frequency and damaging probability, individual genotyping of all deleterious rare variants was performed in patients from the original cohort, and stratified to concomitant cardiac conditions differing between the study and stroke groups. We demonstrated a statistically significant increase in the number of rare and potentially damaging variants in some of the investigated genes in the LVIS pool (an increase in the genomic variants burden). Furthermore, we identified an association between LVIS and 6 rare functional and damaging variants in the Kv7.1 potassium channel gene (KCNQ1). The predicted functional properties (partial loss­of function) for the three most damaging variants in KCNQ1 coding locus were further confirmed in vitro by analyzing the membrane potential changes in cell lines co­transfected heterogeneously with human muscarinic type 1 receptor and wild­type or mutated KCNQ1 cDNA constructs using fluorescence imaging plate reader. The study demonstrated an increased rare variants burden for 54 genes associated with platelet function, and identified a putative role for rare damaging variants in the KCNQ1 gene on LVIS susceptibility in the Polish population.

High incidence and clinical characteristics of fibromuscular dysplasia in patients with spontaneous cervical artery dissection: The ARCADIA-POL study.

The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.

Cytokines in the pathogenesis of hemophilic arthropathy.

Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia. Clinical and subclinical joint bleeding episodes gradually lead to irreversible changes manifesting themselves as pain, progressing ankylosis, marked limitation of the range of motion, muscle atrophy and osteoporosis commonly concomitant with joint deformity resulting from chronic proliferative synovitis and both cartilage and bone degeneration leading to the final functional impairment of the joint. In spite of numerous studies, the pathophysiology of HA has not been fully elucidated, especially as regards immunopathological mechanisms which are associated with the subclinical and early stage of the disease and to be more precise, with chronic joint inflammation. It needs to be emphasized that the pathophysiological processes occurring in a joint with HA are most probably highly mediated by interactions within the cytokine network and other inflammatory mediators present in the tissues of affected joint. Among numerous compounds participating in the induction of an inflammatory process in the pathogenesis of HA, cytokines seem to play a leading role. The most important group controlling the disease seems to be well known inflammatory cytokines, including IL-1ß, TNFα and IL-6. The second group with antagonistic effect is formed by anti-inflammatory cytokines such as IL-4 and IL-10. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of HA with respect to cellular and intracellular signaling pathways is still under investigation. This review, summarizes and discusses the current knowledge about cytokine network in the pathogenesis of HA, indicating possible molecular and cellular mechanisms that may provide potential new therapeutic directions.

The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson's disease.

BACKGROUND/AIMS: Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson's disease (PD) is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to the abundant PDE 4 and 10 expression in the striatum. The present study for the first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. METHODS: IBD [0, 20, 30, 40, or 50 mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg) intoxication. High-pressure liquid chromatography, Western blot analysis, and real time RT-PCR methods were applied. RESULTS: Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF) production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1ß expression. CONCLUSION: IBD had a well-defined effect on astroglial activation in the mouse model of PD; however, there was no protective effect in the acute phase of injury. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration.

Ibudilast: a non­selective phosphodiesterase inhibitor in brain disorders.

Ibudilast (IBD) is a non­selective (3, 4, 10, 11) phosphodiesterase (PDE) inhibitor, used mainly as a bronchodilator for the treatment of bronchial asthma. PDE play a central role in cellular function (e.g. differentiation, synaptic plasticity and inflammatory response) by metabolizing cyclic nucleotides. The results from preclinical and clinical studies indicate that IBD has a broader range of action through suppression of pro­inflammatory cytokines (IL­6, IL­1ß, TNF­α), toll­like receptor 4 blockade (TLR­4), inhibition of a macrophage migration inhibitory factor (MIF), up­regulation the anti­inflammatory cytokine (IL­10), and promotion of neurotrophic factors (GDNF, NGF, NT­4). Recent data indicate that the efficacy of IBD appears to be independent from PDE inhibition activity and rather linked to glial activity attenuation. Additional advantages of IBD, such as crossing the blood-brain barrier, good tolerance and activity by oral administration, makes it a promising therapeutic candidate for treating neuroinflammatory conditions, where the currently available treatment remains unsatisfying due to poor tolerability and/or sub­optimal efficacy. IBD has no direct receptor affinity with exemption of some undefined effect on adenosine receptors that makes the drug devoid of its receptors­mediated adverse effects. Current article provides an overview of the pharmacology of IBD with a focus on preclinical and clinical data supporting its potential neuroprotective benefits for neurological conditions, including multiple sclerosis, neuropathic pain, medication overuse headache, stroke, opioid, alcohol and methamphetamine abuse.

Changes in pre-hospital management of vascular risk factors among patients admitted due to recurrent stroke in Poland from 1995 to 2013.

INTRODUCTION: The aim of this study was to investigate long-term trends in secondary stroke prevention through management of vascular risk factors directly before hospital admission for recurrent stroke. MATERIAL AND METHODS: This is a retrospective registry-based analysis of consecutive recurrent acute stroke patients from a highly urbanized area (Warsaw, Poland) admitted to a single stroke center between 1995 and 2013 with previous ischemic stroke. We compared between four consecutive time periods: 1995-1999, 2000-2004, 2005-2009 and 2010-2013. RESULTS: During the study period, 894 patients with recurrent strokes were admitted (18% of all strokes), including 867 with previous ischemic stroke (our study group). Among those patients, the proportion of recurrent ischemic strokes (88.1% to 93.9%) (p = 0.319) and males (44% to 49.7%) (p = 0.5) remained stable. However, there was a rising trend in patients' age (median age of 73, 74, 76 and 77 years, respectively). There was also an increase in the use of antihypertensives (from 70.2% to 83.8%) (p = 0.013), vitamin K antagonists (from 4.8% to 15.6%) (p = 0.012) and statins (from 32.5% to 59.4%) (p < 0.001). Nonetheless, 21% of patients did not receive any antithrombotic prophylaxis. Tobacco smoking pattern remained unchanged. CONCLUSIONS: Our data indicate a clear overall improvement of secondary stroke prevention. However, persistent use of antithrombotic drugs and tobacco smoking after the first ischemic stroke is constantly suboptimal.

Matrix Metalloproteinase 9 in Epilepsy: The Role of Neuroinflammation in Seizure Development.

Matrix metalloproteinase 9 is a proteolytic enzyme which is recently one of the more often studied biomarkers. Its possible use as a biomarker of neuronal damage in stroke, heart diseases, tumors, multiple sclerosis, and epilepsy is being widely indicated. In epilepsy, MMP-9 is suggested to play a role in epileptic focus formation and in the stimulation of seizures. The increase of MMP-9 activity in the epileptic focus was observed both in animal models and in clinical studies. MMP-9 contributes to formation of epileptic focus, for example, by remodeling of synapses. Its proteolytic action on the elements of blood-brain barrier and activation of chemotactic processes facilitates accumulation of inflammatory cells and induces seizures. Also modification of glutamatergic transmission by MMP-9 is associated with seizures. In this review we will try to recapitulate the results of previous studies about MMP-9 in terms of its association with epilepsy. We will discuss the mechanisms of its actions and present the results revealed in animal models and clinical studies. We will also provide a comparison of the results of various studies on MMP-9 levels in the context of its possible use as a biomarker of the activity of epilepsy.

Readiness Visual Analog Scale: A Simple Way to Predict Post-Stroke Smoking Behavior.

BACKGROUND AND PURPOSE: The aim of the present study was to assess a relationship between readiness to quit and post-stroke smoking behavior. METHODS: Eighty-six active smokers with first-ever ischemic stroke were recruited in a tertiary-care stroke unit. The question "Are you ready to quit smoking within the next month?" with yes/no responses and the 10-cm readiness visual analog scale (VAS) was administered during the anti-smoking intervention. Smoking status was verified at the 3- and 12-month follow-up. RESULTS: The readiness VAS score at hospitalization was significantly lower in patients classified as smokers as compared to patients classified as non-smokers. The readiness score <5 cm was a significant predictor of smoking at the 3-month (OR, 7.3) and 12-month follow-up (OR, 4.9). CONCLUSIONS: The present results suggest that the readiness VAS can be used as a simple and inexpensive instrument for early identification of patients who continue to smoke after stroke.

Anti-myelin basic protein T cells protect hippocampal neurons against trimethyltin-induced damage.

We investigated the influence of administration of autoimmune T cells on trimethyltin-induced degeneration of hippocampal neurons. Female Lewis rats received 8 mg/kg trimethyltin intraperitoneally alone, or followed 24 h later by a second intravenous injection of anti-myelin basic protein T cells (green fluorescent protein-tagged). Neurodegeneration was assessed by NeuN and Nissl cell counts 21 days after trimethyltin injection. We found that neurodegeneration in the CA4 region of the hippocampus was significantly reduced in the group receiving T cells. T cells also caused an augmentation of trimethyltin-induced hippocampal astrocytic activation and astrocytic TrkA expression, which was particularly intense in the CA4 region. Our study provides the first evidence of neuroprotection evoked by transferred T cells following a neurotoxic brain insult. The data suggest that mediation of the neuroprotective effects of T-cell-released nerve growth factor occurs mainly via hippocampal astroglial TrkA receptors.

Dopamine, serotonin and noradrenaline changes in the striatum of C57BL mice following myelin oligodendrocyte glycoprotein (MOG) 35-55 and complete Freund adjuvant (CFA) administration.

Many data suggest involvement of inflammation in neurodegeneration. However, the exact mechanisms of this cooperation are poorly understood. We have previously shown that induction of inflammatory reaction, both before and after injury of the striatum, affects regeneration of dopaminergic neurons. In the present research we studied the role of inflammatory reaction in non-injured striatum. We used myelin oligodendrocyte glycoprotein (MOG) 35-55 in complete Freund's adjuvant (CFA) to elicit experimental autoimmune encephalomyelitis (EAE) mice model. As determined by HPLC, striatal dopamine (DA) and serotonin levels in mice treated with either MOG 35-55 in CFA or CFA alone were significantly higher compared to vehicle-treated controls on 13th day after induction. The ratio of homovanilic acid/dopamine (HVA/DA) and 3, 4 dihydroxyphenylacetic acid/dopamine (DOPAC/DA) were significantly lower in the MOG and CFA groups on 13th day, indicating decreased DA metabolism. Noradrenaline (NA) concentration did not differ between groups. Moreover, the striatal mRNA IL-1beta and TNF-alpha levels were elevated during induction phase of EAE in both groups, as determined by RT-PCR. Our data indicate regulatory connection between dopaminergic and immune systems.

Gender differences in neurological disease: role of estrogens and cytokines.

Increasing evidence suggests that inflammatory response may be a critical component of different brain pathologies. However, the role played by this reaction is not fully understood. The present findings suggest that neuroinflammtory mediators such as cytokines may be involved in a number of key steps in the pathological cascade of events leading to neuronal injury. This hypothesis is strongly supported by experimental and clinical observations indicating that inhibition of the inflammatory reaction correlates with less neuronal damage. Estrogens are thought to play a role in the sex difference observed in many neurological diseases with inflammatory components including stroke, Alzheimer's and Parkinson's diseases, multiple sclerosis, or amyotrophic lateral sclerosis. Clinical and experimental studies have established estrogen as a neuroprotective hormone in these diseases. However, the exact mechanisms involved in the neuroprotective effects of estrogens are still unclear. It is possible that the beneficial effects of these hormones may be dependent on their inhibitory activity on the inflammatory reaction associated with the above-mentioned brain pathologies. Here, we review the current clinical and experimental evidence with respect to the inflammation-modulating effects of estrogens as one potential explanatory factor for sexual dimorzphism in the prevalence of numerous neurological diseases.

Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease.

The inflammatory reaction and oxidative stress has been linked with PD. Proinflammatory cytokines promote neurodegeneration or neuroprotection in different animal models. In addition, these cytokines have been reported to increase iNOS expression. With the RT-PCR method we evaluated mRNA levels for IL 1beta, IL6, TNF, IFNgamma, IL-10 and iNOS in the striatum of C57BL/6 mice after MPTP intoxication. The IL1beta mRNA expression rapidly increased and peaked at 6 h. The first increase of mRNA for TNFalpha and IFNgamma was noticed at 6-24 h and the second at the 7th day after MPTP intoxication. Two peaks of IL10 mRNA were seen, immediately (6 h) and at the 3 day post MPTP injection. The peak of mRNA level for IL6 was observed at the 7th day. Expression of mRNA for iNOS peaked at 24 h, started decreasing on the 3rd day, but was still present till the 14th day. Those findings suggest that cytokine network and iNOS may be involved in the development of immune changes accompanying degeneration of the nigrostriatal system.

Concomitant heterozygous factor V Leiden mutation and homozygous prothrombin gene variant (G20210A) in patient with cerebral venous thrombosis.

BACKGROUND: Factor V Leiden mutation represents the most common genetic risk factor of venous thrombosis in Caucasian population. A common mutation in prothrombin gene, which is due to G-->A transition at position 20210, is also associated with elevated prothrombin concentration and thrombosis. Both this mutations may constitute concomitant risk factors for deep venous thrombosis. CASE REPORT: A 29-years old woman was admitted in the Emergency Department because of severe headache with vomiting that she suffered for a few days without any neurological deficits. In the Emergency she presented first in her life tonic-clonic seizures followed by right hemiparesis and aphasia and than was admitted to hospital. CT and MR scan showed a large lesion in the left fronto-parietal region with extent edema, which was first diagnosed as tumor. Following MR showed more lesions and typical signs of sinus thrombosis. She improved quickly after stroke without any anticoagulant treatment. Genetic study revealed factor V Leiden mutation and homozygous mutation G20210A in prothrombin gene. CONCLUSIONS: Both mutations found in this case, alone, are not a high risk factors for venous thrombosis but together may increase 5-10 fold risk of venous thrombosis. Venous stroke must be considered always in acute neurological events with organic brain lesions, especially in young

Immune processes in the pathogenesis of Parkinson's disease - a potential role for microglia and nitric oxide.

It has been known for many years that immune system alterations occur in Parkinson's disease (PD). Changes in lymphocyte populations in cerebrospinal fluid and blood, immunoglobulin synthesis, and cytokine and acute phase protein production have been observed in patients with PD. In this regard, PD patients exhibit a lower frequency of infections and cancer, suggesting that immune system stimulation may occur. This hypothesis is further supported by the observation of T-cell activation leading to the production of interferon gamma in PD. As in other CNS degenerative diseases, in damaged regions in the brains of PD patients, there is evidence of inflammation, characterized by glial reaction (especially microglia), as well as increased expression of HLA-DR antigens, cytokines, and components of complement. These observations suggest that immune system mechanisms are involved in the pathogenesis of neuronal damage in PD. The cellular mechanisms of primary injury in PD have not been clarified, however, but it is likely that mitochondrial mutations, oxidative stress and apoptosis play a role. Furthermore, inflammation initiated by neuronal damage in the striatum and the substantia nigra in PD may aggravate the course of the disease. These observations suggest that treatment with anti-inflammatory drugs may act to slow progression of PD.