Sławomir Budrewicz

Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.

Introduction Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson’s disease (PD) remains controversial. Objectives The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A). Methods A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson’s Disease Rating Scale score, Hoehn–Yahr staging, and the Schwab–England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1). Results The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41–0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42–0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 &mgr;mol/l) as compared with the controls (14.0±9.6 &mgr;mol/l, P=10–8) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients. Conclusion The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Myometry revealed medication-induced decrease in resting skeletal muscle stiffness in Parkinson's disease patients

BACKGROUND Based on combined analysis of clinical assessment of parkinsonian rigidity (constant resistance force generated during passive movement in a joint), electromyography and/or dynamometry many studies showed objectively that anti-parkinsonian medication decreases the rigidity in Parkinsons disease (PD). Rigidity-related changes in resting muscle stiffness (changed muscles mechanical property related to its structural changes and changed neural drive) in PD patients have been revealed by myometry, a simple, sensitive, and reliable method for measuring mechanical properties in human soft tissues. However, an application of myometry in estimation of medication effects on the PD rigidity-related muscle stiffness has not been reported yet. Therefore, our study aimed to assess medication-induced changes in resting muscle stiffness in PD patients using myometry. METHODS We measured resting muscle stiffness by myometry and recorded a surface electromyogram of relaxed biceps brachii, brachioradialis and triceps brachii muscles in ten patients with PD (age: 51-80 years; Hoehn and Yahr stage: 2.5-4) during medication on-phase (when subjects felt best comfort and fitness after medication: Levodopa, Piribedil, Ropinirol) and medication off-phase (12h after withdrawal of the medication). FINDINGS Our patients had significantly lower myometric stiffness and electromyogram amplitude in all tested muscles, and also lower clinical rigidity scores during the medication on-phase compared with the medication off-phase. INTERPRETATION Myometry revealed that anti-parkinsonian medication decreases not only rigidity in PD, but also rigidity-related stiffness in resting skeletal muscles in PD patients. These findings show that myometry can enrich neurological practice, by allowing objective and reliable assessment of parkinsonian rigidity treatment effectiveness.

The impact of MRI white matter hyperintensities on dementia in Parkinson's disease in relation to the homocysteine level and other vascular risk factors.

Background: The role of white matter hyperintensities (WMH) and homocysteine (Hcy) and other vascular risk factors in the pathogenesis of Parkinsons disease (PD) dementia (PDD) remains unclear. Objective: The aim of the study was to assess the impact of WMH, Hcy and other biochemical and vascular risk factors on PDD. Methods: A total of 192 patients with PD and 184 age- and sex-matched healthy controls were included. A semistructured interview was used to assess demographic and clinical variables with respect to vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, ischemic heart disease, obliterative atherosclerosis, hypercholesterolemia, smoking, alcohol intake). Unified Parkinsons Disease Rating Scale score, Hoehn-Yahr staging and the Schwab-England activities of daily living scale were used to assess motor abilities and activities of daily living. A complex neuropsychological examination with a battery of tests was used to classify patients into a group with dementia (PDD) and a group without dementia (PD). Neuroradiological examination of MRI scans included visual rating scales for WMH (according to the Wahlund and Erkinjunntti rating scales) and the Scheltens scale for hippocampal atrophy. Blood samples for Hcy, folate, vitamin B12, fibrinogen, lipids, glucose, creatinine, transaminases and thyroid stimulating hormone (TSH) were examined. Results: Among all patients, 57 (29.7%) fulfilled the diagnostic criteria for dementia. Significantly higher Hcy plasma levels were noted in PD and PDD groups compared to controls (p < 0.05) and in PDD when compared to PD (p < 0.05). According to multivariate regression analysis, WMH (Erkinjuntti scale), high Hcy, low vitamin B12 and folate plasma levels were independent risk factors for PDD. Vascular risk factors did not play any role in the pathogenesis of PDD and WMH. Conclusions: WMH along with Hcy, folate and vitamin B12 may impact cognition in PD. Therapy with vitamin B12, folate and catechol-O-methyltransferase inhibitors may play a potential protective role against PDD.

Increased muscle belly and tendon stiffness in patients with Parkinson's disease, as measured by myotonometry

Based on Daviss law, greater tonus of the muscle belly in individuals with Parkinsons disease can create greater tension in the tendon, leading to structural adjustment and an increase in tendon stiffness. Our study aimed to separately assess passive stiffness in the muscle belly and tendon in medicated patients with Parkinsons disease, using myotonometry.

Composed Paraneoplastic Neurological Syndrome, Disseminated in Time and Space, in the Course of Non-Small Cell Neuro-Endocrine Lung Cancer

Introduction: Paraneoplastic neurological syndrome is a rare complication of different types of cancer. Non-small cell neuro-endocrine lung cancer is very rare and there are few descriptions of paraneoplastic syndrome in patients with such types of cancer. Paraneoplastic movement disorders, among them chorea, have an exceptionally rare occurrence. Clinical presentation: A 64-year-old woman presented paraneoplastic chorea with non-typical coincidence of anti-Hu and anti-GD1b antibodies. Chorea was the last sign of the disease and was comorbid with encephalitis, chronic polyradiculoneuropathy and autonomic dysfunction; the clinical symptoms were disseminated in time. A very rare type of lung cancer i.e., poorly differentiated non-small cell neuroendocrine cancer was found. Conclusions: The diversity of the clinical picture in this patient with non-small cell neuro-endocrine lung cancer can be explained by the complexity of the neurological pathomechanisms of paraneoplastic syndromes.

Acute hyperkinetic syndrome due to ephedrone abuse.

Objectives:A new form of manganese poisoning is related to the intravenous use of self-prepared methcathinone hydrochloride (ephedrone). Manganese encephalopathy typically manifests as a levodopa-resistant parkinsonism. Main Points:A 32-year-old drug-addicted man with acute gait disturbances after the ephedrone injections was presented. Choreic movements, severe postural instability, and “cock-walk” gait were observed. Magnetic resonance imaging T1 images showed high signal intensity of white matter in the basal ganglia and pituitary gland, and T2 images showed decreased signal mostly of globus pallidus with decreased N-acetylaspartate and choline levels in MR spectroscopy. Conclusions:The unusual pattern of MR imaging may explain the unusual clinical symptoms with dominant hyperkinetic syndrome.

Diagnostic Difficulties in Primary Pauci-Melanotic Leptomeningeal Melanomatosis

We present a rare case of primary malignant melanoma of the central nervous system. We underline the difficulties we faced during diagnostic procedures. Finally, postmortem examination revealed the diagnosis of primary pauci-melanotic leptomeningeal melanomatosis.

Clinical and nutritional correlations in Parkinson's disease: Preliminary report.

BACKGROUND Parkinsons disease (PD) is one of the most common neurodegenerative disorders. Malnutrition is an essential problem in the late stage of PD. Lowering of body mass is seen in 30% of patients, and malnutrition or the risk of malnutrition in 24% and 60%, respectively. OBJECTIVES The aim of the study was an analysis of the relationships between the parameters of the nutritional stage and the advancement of clinical symptoms in PD patients. MATERIAL AND METHODS A total of 40 patients (18 men, 22 women) with PD were analyzed, mean age: 70.7 years. In all patients, structured anamnesis, Nutrition Risk Screening (NRS 2002), body mass index (BMI), morphology, and basic biochemical tests were conducted. Skin fold thickness was also measured. The results were referred to the score of different scales. RESULTS The study showed a lot of correlations between the severity of PD, mostly motor symptoms in the Unified Parkinsons Disease Rating Scale (UPDRS), and parameters characterizing the patients nutritional status. We revealed a correlation between malnutrition and PD duration, and l-DOPA frequency intake. The global score of parts I, II and III of UPDRS were correlated with the nutritional status. The results confirmed the existence of more severe smell change and taste impairment in the late stage of PD, with more pronounced malnutrition. CONCLUSIONS The duration of PD, motor and non-motor PD symptoms, and the frequency of l-DOPA intake closely correlate with the nutritional status. Understanding of the multifactorial interdependence might be useful in the estimation of the algorithm for monitoring the nutritional status of PD patients and taking early nutritional intervention.

Dynamics of Magnetic Resonance Image Changes in a Patient with Creutzfeldt-Jakob Disease

apraxia, extrapyramidal symptoms and motor perseveration were noted ( fig. 1 a, d), in the progression stage (third month with generalized myoclonus, severe deterioration) ( fig. 1 b, e) and in the last phase (fourth month) with akinetic mutism and autonomic dysfunction ( fig. 1 c, f). The authors indicate the possibility of employing new MRI techniques in the assessment of the changes in cerebral dynamics and their correlations with clinical symptoms in Creutzfeldt-Jakob disease patients [1, 2] . Magnetic resonance proton spectroscopy and diffusion-weighted images were conducted on a 61-year-old woman with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease, with positive 14-3-3 protein. Initially, EEG showed delta waves paroxysmal discharges, then sluggish basic activity with periodic sharp and slow wave complexes. Consecutive neuroimages were performed at the beginning of the disease (second month) when cognition and behavioral impairment, aphasia, Received: January 15, 2013 Accepted: May 8, 2013 Published online: July 25, 2013