Abstract: CONTEXT: Epothilones, belonging to the family of microtubule stabilizing agents, have shown prolonged remissions and improved survival in various types of refractory, treatment-resistant cancer. Ixabepilone (BMS-247550) is the main representative of these compounds. Peripheral neuropathy is a significant toxicity of epothilones, eventually resulting in dose modification and changes in the treatment plan. OBJECTIVES: This review critically looks at the pathogenesis, incidence, risk factors, characteristics, and management of epothilone-induced peripheral neuropathy (EIPN). We also highlight areas of future research to pursue. METHODS: References were identified by searches of PubMed from 2000 until December 2010 with related terms. RESULTS: The mechanism underlying EIPN remains rather unclear. Damage to the ganglion soma cells and peripheral axons through disruption of microtubules of the mitotic spindle and by interference with the axonal transport in the affected neurons may significantly contribute to the pathogenesis of EIPN. As a result, epothilones primarily produce an axonal, dose-dependent, sensory distal peripheral neuropathy, which is reversible in most cases on discontinuation of treatment. The incidence of EIPN is mainly related to risk factors, including cumulative dose and probably pre-existing neuropathy. To date, apart from the use of dose reduction and schedule change algorithm, there is no effective treatment with neuroprotective agents for EIPN. CONCLUSION: EIPN remains a very challenging area in the field of toxic neuropathies. As such, there is a need for further preclinical and prospective clinical studies to elucidate the pathogenesis of EIPN and provide further robust evidence on its incidence, course, and reversibility.
Abstract: To our knowledge, we describe for the first time the case of a male patient with sporadic young-onset amyotrophic lateral sclerosis, most likely attributed to chronic regular cocaine use and abuse. Our case supports the view that cocaine use and abuse may trigger a process of motor neuron degeneration by mechanisms implicating alterations in the neurobiology of the excitatory neurotransmitter glutamate and its receptors.
Abstract: The first objective of the current observational study was to assess the degree of religiosity in Greek Christian Orthodox primary caregivers of patients with multiple sclerosis (MS). The second objective was to evaluate the interrelations between religiosity and quality of life (QOL) and to identify the determinants of QOL, an endpoint of considerable importance in clinical research and practice. Twenty-two male and 13 female primary caregivers (mean age 47.3 ± 12.4 years) of an equal number of patients with MS, who consented to participate, completed the Systems of the Greek version of the Belief Inventory (SBI-15R) and the Greek validated version of EuroQOL (EQ-5D). The analysis revealed high scores on religiosity, especially among females. Caregivers scored in the religious beliefs and practices subscale of SBI-15R with a mean score of 22.8 ± 7.8 (range 0-30) and with 7.1 ± 4.8 (range 0-14) in the social support subscale. However, both of the SBI-15R domains were almost unrelated to the degree of overall QOL. There was only a reliable (but with little clinical value) association between the pain/discomfort domain of the EQ-5D with the SBI-15R beliefs and practices subscale (r = -0.38, p = 0.03). Although high levels of religiosity among Greek Christian Orthodox primary caregivers of MS patients were evident, this study did not demonstrate any beneficial effect of religious beliefs and practices on their QOL. Further prospective studies with a population with the same and/or diverse religious and cultural backgrounds are needed to better elucidate the complex association between religiosity and QOL in primary caregivers of MS patients.
Abstract: PURPOSE: Our aim was to assess the perceived emotional burden and quality of life (QOL) in a sample of Greek primary caregivers of patients with multiple sclerosis (MS). METHODS: Twenty-two male and 13 female primary caregivers (mean age 47.3 ± 12.4 years), and an equal number of patients with MS, completed the Greek validated version of the hospital anxiety and depression scale (HADS) and the Greek validated version of EuroQOL (EQ-5D). Thirty-five age-, gender-, and education-matched healthy controls were used for comparison. RESULTS: Caregivers experienced higher degree of anxiety than depression. The mean score of the HADS-A subscale was 9.5 ± 4 (range 3-15), and the mean score of the HADS-D subscale was 7.1 ± 3.1 (range 2-14). The mean scores of caregivers on both HADS-A and HADS-D were significantly higher than the controls' (P < 0.0001). Twenty-two caregivers were diagnosed with manifesting anxiety, whereas 12 of them also presented depression. Highly educated caregivers were more prone to manifest increased levels of anxiety and depression. The increased psychological distress was further supported by the responses in the anxiety/depression dimension on the EQ-5D: 27 reported a moderate level of anxiety/depression and three indicated an extreme degree. The caregivers reported a mean EQ-VAS value of 61.9 ± 13.8 (range 40-100), with 10 caregivers rating their health status a score of 50 or lower; the controls scored significantly higher (90.3 ± 7.1; P < 0.0001). CONCLUSION: The sample of caregivers we studied was psychologically burdened to a significant degree, a fact that obviously deteriorates their QOL. Appropriate psychopharmacological interventions are warranted to reduce caregivers' burden.
Abstract: CONTEXT: Several studies have investigated the prevalence of sleep disorders in patients suffering from multiple sclerosis (MS) and have shown that up to 54% of patients may have significantly more sleep problems than the general population. To our knowledge, however, no data are available about the quality of sleep of the primary caregivers of patients with MS. OBJECTIVES: The objectives of the current cross-sectional study were to assess the quality of sleep in Greek primary caregivers of patients with MS and to investigate its relationships with the degree of caregivers' emotional distress. METHODS: Twenty-two male and 13 female primary caregivers (mean age 47.3±12.4 years) of an equal number of patients with MS, who consented to participate, completed the validated Greek version of the Pittsburgh Sleep Quality Index (PSQI) and the validated Greek version of the Hospital Anxiety and Depression Scale (HADS). Thirty-five age-, gender-, and education-matched healthy controls were used for comparisons. RESULTS: Caregivers experienced a higher degree of anxiety than depression. The mean score in the seven-item HADS-A subscale was 9.5±4 (range 3-15) and the mean score in the seven-item HADS-D subscale was 7.1±3.1 (range 2-14). The mean scores of caregivers on both HADS-A and HADS-D were significantly higher than those of controls (P<0.001). The PSQI scoring demonstrated that 19 (54.3%) caregivers had poor sleep quality (cut-off value of >5). The mean values of caregivers in the PSQI were 6.0±2.8 (range 2-12) compared with controls, who scored at a significantly lower level (1.5±0.8; P<0.001). Poor quality of sleep was significantly correlated with increased levels of anxiety (r=0.392; P=0.02) and depression (r=0.424; P=0.01). Among the PSQI components, the sleep duration and sleep latency were mostly influenced by the degree of emotional distress. CONCLUSIONS: A significant proportion of primary caregivers of MS patients experience poor sleep quality. The degree of their emotional distress appears to significantly influence their quality of sleep. Appropriate psychopharmacological interventions may be required for those individuals.
Abstract: The effect of different doses of X(-)rays on apoptosis, proliferation, epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP-2) expression was investigated in a human glioblastoma cell line.
Abstract: To assess the significance of the ITGB3 polymorphism at residue 33 (ITGB3 L33P) in the development of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN).
Abstract: We sought to identify significant ulnar nerve conduction abnormalities and also to detect ulnar F-wave variable changes in patients with secondary progressive multiple sclerosis (MS). Conventional conduction study was performed unilaterally to ulnar nerves of eight men and 12 women with secondary progressive MS (mean age, 47.5 +/- 6.6 years), having spastic hemiparesis and hand spasticity. A series of 40 electrical stimuli were also delivered to their ulnar nerves unilaterally so as to obtain F waves. The side of examination was ipsilateral to the side of spastic paresis. The following F-wave variables were estimated: F-wave persistence, latency, amplitude, duration, and F chronodispersion. Ten patients with remitting-relapsing MS without any evidence of hand spasticity and 20 age- and gender-matched healthy volunteers served as controls. Motor and sensory conduction study was normal in all participants. The F-wave persistence, latency, and duration parameters and also the F chronodispersion were comparable between groups. The mean and maximum F-wave amplitude values (P = 0.005) and the F mean/M (P = 0.001) and F maximal/M (P = 0.001) ratios were significantly higher than those of controls. Finally, the F-wave amplitude parameters in patients with secondary progressive MS significantly correlated with the degree of spasticity and the duration of disease. Significant amplitude F-wave abnormalities occurred in patients with secondary progressive MS and hand spasticity, emphasizing the contribution of upper motor neurons damage in the genesis of F waves.
Abstract: CONTEXT: In recent years, there is growing evidence in the medical literature to support an association between administration of commonly used chemotherapeutic agents and an increased risk for cognitive impairment. OBJECTIVES: We herein critically summarize data relating to the pathophysiological mechanisms by which chemotherapy may induce cognitive impairment in patients surviving from solid tumors. The clinical and epidemiological characteristics and the proposed management strategies to counter chemotherapy-induced cognitive impairment (CICI) are also presented. METHODS: References for this review were identified by searches of PubMed from 1995 until December 2009 with related terms. RESULTS: Both the pathogenetic mechanisms and the overall clinical nature of CICIÂ remain vaguely defined. Findings indicate that CICI is a relatively common event that, in most of the cases, remains underdiagnosed, thereby adversely affecting the quality of life of patients with cancer. Effective pharmacological interventions toward the symptomatic or prophylactic management of CICI are also lacking. CONCLUSIONS: Either called "chemobrain" or "chemofog," the long-term CICI in cancer survivors is real. The need for multidisciplinary care interventions toward a timely diagnosis and management of CICI is clearly warranted.
Abstract: Peripheral neuropathy ranks among the most common non-haematological adverse effects of a number of effective chemotherapeutic agents, including platinum compounds, taxanes and vinca alkaloids. Newer agents, such as bortezomib, thalidomide and lenalidomide, frequently exert similar neurotoxic effects on peripheral nerves. Chemotherapy-induced peripheral neuropathy (CIPN) may result from a variety of mechanisms and may be related to causal factors, such as single dose per course, cumulative dose and risk factors including treatment schedule, prior or concomitant administration of other neurotoxic agents, age and pre-existing peripheral neuropathy of other causes. The symptoms usually begin during chemotherapy and they may even worsen after cessation of treatment. In most of the cases, patients experience positive (pain, paresthesias) or negative (numbness) sensory symptoms in distal extremities in a stocking-and-glove distribution with less prominent motor and autonomic involvement. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested in preclinical models and clinical open label or randomized controlled trials for their ability to prevent or treat symptoms of CIPN. Although several of these agents hold promise as possible neuroprotective factors, clinical data are still controversial and none have as yet robustly been proven effective against CIPN. This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of peripheral neuropathy associated with commonly used chemotherapeutic agents. We also highlight areas of future research to pursue.
Abstract: The aim of this study was to assess the antitumour effect of an anti-VEGFR (sunitinib) and the anti-EGFR multi-targeted agent (lapatinib), applied either alone or in combination on the migration capacity of two glioma cell lines. Furthermore, this study sought to evaluate the effect of lapatinib in the formation of EGFR-integrin β(1) complex, as well as the effect of sunitinib in the VEGFR-integrin β(3) and PDGFR-integrin β(3) complexes formation.
Abstract: This review critically evaluates current knowledge of molecularly targeted therapies of malignant gliomas.Various molecularly targeted single-agent therapies, including targeted therapies of growth and survival, have been evaluated in clinical trials but have failed to demonstrate a significant survival benefit compared with standard treatment regimens. The efficacy of multitargeted kinase inhibitors or combinations of single-targeted kinase inhibitors is a promising strategy, but requires additional clinical evaluation before definitive conclusions can be made. Important areas for further research include the assessment of serum or tissue biomarkers, the elucidation of prognostic molecular markers, and the determination of whether the mechanism of action of a drug is appropriate to the genetic alterations observed within individual tumors.
Abstract: Malignant gliomas (MGs), including glioblastomas and anaplastic astrocytomas are the most common primary brain tumors. Despite treatment advances, the outcome of patients diagnosed with MGs is poor. The current standard treatment protocols for managing these tumors include maximally safe surgical resection, followed by fractioned radiation therapy of the tumor and surrounding brain parenchyma. Until recently, the use of systemic chemotherapy was restricted and ineffective, due to the fact that the blood brain barrier inhibits the adequate therapeutic concentrations of most chemotherapeutic agents into the tumor and peritumoral area. Genetic transformation, like the expression of the DNA repair enzyme methylguanine methyltransferase (MGMT) and specific characteristics of these neoplasms are also causal factors, accounting for the development of treatment resistance to standard chemotherapy options with alkylating compounds. Recent advances, mostly, in thorough understanding of the complex molecular pathogenesis of MGs have led to arousal of rational development of new molecularly targeted treatment options that simultaneously affect multiple signalling pathways. Currently, several molecularly targeted agents, like tyrosine kinase and growth factor inhibitors have been tested in clinical trials to establish future directions in the therapy of MGs. A number of novel targeted strategies, including among others radio-immuno and ligand-toxin conjugates and RNA-based therapies, are also under investigation. We herein review and discuss the standard treatment options and recent advances in the therapy of MGs, with emphasis on the current knowledge towards the molecular pathogenesis of MGs as well as molecularly targeted therapies. We also highlight areas of future research.
Abstract: To assess the significance of the second lumbrical-interosseous latency (2LI-DML) comparison in the diagnosis of carpal tunnel syndrome (CTS).
Abstract: This review focuses on the recent advances in clinical data regarding antibody-based therapy in the management of solid tumors. We also discuss perspectives on antibody-based therapy in the future. Thorough understanding of the complex interactions between components of the immunological response has led to interest in the concept of immune-mediated therapy for solid tumors. Over the last few years, several humanized and chimeric monoclonal antibodies (MAbs) targeting human epidermal receptor 2 (HER2), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) have been employed in treating solid tumors, including breast, colorectal, lung, head and neck, and gynecologic cancers. Trastuzumab, bevacizumab, cetuximab, and panitumumab are MAbs that are most widely used in clinical practice with acceptable rates of adverse events. Combination of MAbs with small-molecule inhibitors of the same pathway could potentially increase the efficacy and specificity of antibody-based treatment. Immune-mediated effects may be further exploited with the use of bivalent molecules.
Abstract: Angiogenesis is considered to be a regulating factor of vascular development and growth for malignant gliomas, including glioblastoma multiforme (GBM) and anaplastic astrocytomas. The mechanism of angiogenesis is primarily mediated by hypoxia through chronic activation of the HIF pathway leading to the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. Alternatively, it can be triggered by genetic factors. The VEGF/VEGFR-2 is the predominant angiogenic signalling pathway in malignant gliomas. Currently, anti-angiogenic molecularly targeted therapies, including administration of monoclonal antibodies or tyrosine kinase inhibitors (TKIs), are being increasingly adopted for treating GBMs. This approach is based on the ability of anti-VEGFRs monoclonal antibodies to decrease vascular permeability and perfusion, whereas the use of TKIs is mainly based on their capacity to interfere with cell communication, receptor signaling and growth of tumours. Our aim is to review current knowledge on angiogenesis as a molecular pathogenetic mechanism of malignant gliomas and to critically look at and discuss antiangiogenic molecularly targeted therapies for these brain malignancies. We also highlight areas of future research to pursue.
Abstract: It was the aim of this study to test the hypothesis that the voltage-gated sodium channel gene SCN2A R19K polymorphism confers liability to oxaliplatin-induced peripheral neuropathy (OXLIPN).
Abstract: Myasthenia gravis (MG) can rarely be manifested with ocular motility disturbances, simulating internuclear ophthalmoplegia. Pseudo-internuclear ophthalmoplegia (PINO) may occur during the course of MG, however, the initial presentation of MG with PINO in rather unlikely. We herein describe the case of a male patient who developed PINO, as an initial manifestation of MG.
Abstract: Conventional treatment options, including corticosteroids, intravenous immunoglobulin, or plasma exchange, often fail to treat dysimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and monoclonal gammopathy with its subtypes. Therefore, a significant percentage of patients require adjunctive immunosuppressive therapies. Considering that even immunosuppressive agents often are ineffective and/or associated with significant toxicities, the need for the development of safe and effective new treatment options is rising. Currently, several monoclonal antibodies (MAbs) have been tested in open-label small-sized studies or even in single cases so as to establish future directions in the therapy of diseases of the peripheral nervous system (PNS). Rituximab, an MAb targeting against the B cell surface membrane protein CD20, is the most widely used and promising MAb for the treatment of dysimmune neuropathies, especially for those in which immunoglobulin M (IgM) autoantibodies are pathogenetically involved. The efficacy of alemtuzumab, bevacizumab, and etanercept to treat various forms of dysimmune neuropathies is currently under investigation. This review looks critically at recent developments in molecularly targeted therapies for dysimmune neuropathies and also highlights areas of future research to pursue.
Abstract: We review and discuss the pathogenesis, epidemiology, diagnosis as well as recent advances in the treatment of NMO. We also highlight areas of future research.
Abstract: The current study sought to longitudinally evaluate the postexercise facilitation of motor evoked potentials (MEP) in two patients during different phases of short-circle depressive-manic disorder. Each study included 50 baseline MEP elicited by transcranial magnetic stimulation, followed by 50 MEP immediately after nonfatiguing exercise of the examined muscle. Postexercise MEP facilitation, expressed as percentage of baseline value, varied from 71% to 119% and from 99% to 107% in each patient, respectively, being significantly lower than our mean normal control value (268%). No differences in MEP facilitation between phases of short-circle depressive-manic disorder were revealed. Reduced postexercise facilitation was independent of the bipolar disorder phases, suggesting an invariable underlying association of the psychiatric pathophysiological mechanisms to impaired cortical excitability.
Abstract: Myoclonus-dystonia (MD) is a rare movement disorder characterized by myoclonic jerks, dystonia and a variety of psychiatric symptoms. Neuroimaging and electrophysiologic studies have not been able to detect any specific central nervous system abnormality. We report for the first time a well-characterized case with MD and abnormal brain perfusion imaging using single photon emission computed tomography (SPECT) with (99m)Tc-ethyl cysteinate dimer (ECD). A review of the literature on the phenotypic and pathogenetic considerations for MD is also presented.
Abstract: Platinum compounds are a class of chemotherapy agents that posses a broad spectrum of activity against several solid malignancies. Oxaliplatin (OXL) is a third-generation organoplatinum compound with significant activity mainly against colorectal cancer (CRC). Peripheral neuropathy is a well recognized toxicity of OXL, usually resulting in dose modification. OXL induces two types of peripheral neuropathy; acute and chronic. The acute oxaliplatin-induced peripheral neuropathy (OXLIPN) may be linked to the rapid chelation of calcium by OXL-induced oxalate and OXL is capable of altering the voltage-gated sodium channels through a pathway involving calcium ions. On the other hand, decreased cellular metabolism and axoplasmatic transport resulting from the accumulation of OXL in the dorsal root ganglia cells is the most widely accepted mechanism of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN). As a result, OXL produces a symmetric, axonal, sensory distal primary neuronopathy without motor involvement. The incidence of OXLIPN is usually related to various risk factors, including treatment schedule, dosage, cumulative dose and time of infusion. The assessment of OXLIPN is primarily based on neurologic clinical examination and quantitative methods, such as nerve conduction study. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested for their ability to prevent OXLIPN. However, the clinical data are still controversial. We herein review and discuss the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of OXLIPN. We also highlight areas of future research.
Abstract: Intramedullary tumors of the spinal cord are rare neoplasms that can be associated with severe neurological and functional handicaps. To our knowledge, we describe for the first time the case of a male patient who developed bilateral drop foot as an initial manifestation of a primary tumor in the conus medullaris of the spinal cord, probably an astrocytoma.
Abstract: Peripheral neuropathy is a well recognized toxicity of taxanes, usually resulting to dose modification and changes in the treatment plan. Taxanes produce a symmetric, axonal predominantly sensory distal neuropathy with less prominent motor involvement. A "dying back" process starting from distal nerve endings followed by effects on Schwann cells, neuronal body or axonal transport changes and a disturbed cytoplasmatic flow in the affected neurons is the most widely accepted mechanism of taxanes neurotoxicity. The incidence of taxanes-induced peripheral neuropathy is related to causal factors, such as single dose per course and cumulative dose and risk factors including treatment schedule, prior or concomitant administration of platinum compounds or vinca alcaloids, age and pre-existing peripheral neuropathy of other causes. The most reliable method to assess taxanes neurotoxicity is by clinical examination combined with electrophysiological evaluation. There is currently no effective symptomatic treatment for paclitaxel-associated pain, myalgias and arthralgias. Tricyclic antidepressants and anticonvulsants have been used as symptomatic treatment of neurotoxicity with some measure of success. Therefore, new approaches for prophylaxis against taxanes-induced peripheral neuropathy are needed. Several neuroprotective agents including, thiols, neurotrophic factors, and antioxidants hold promise for their ability to prevent neurotoxicity resulting from taxanes exposure. However, further confirmatory trials are warranted on this important clinical topic. This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of taxanes-induced peripheral neuropathy. We also highlight areas of future research.
Abstract: Painful limbs/moving extremities (PLME) is a disorder characterized by spontaneous, complex, slow (1-2 Hz) involuntary toe or finger movements. The movements that can be bilateral or unilateral are usually accompanied by pain in the affected limbs. Painless variants are less common. PLME has been associated with peripheral and central nervous system disease although idiopathic cases have been reported. Its etiopathogenesis is unknown and treatment approaches remain largely empirical. Nerve blocks and botulinum toxin type A injections as well as oral medication have had some measure of success. Current theories suggest that central oscillator(s) at the spinal or supraspinal levels may be involved. Future research in PLME should include prospective electrophysiological and functional imaging studies as well as clinical trials with botulinum toxin injections and oral pharmacological agents.
Abstract: The present study sought to determine the prevalence of emotional distress and evaluate demographic and clinical factors related to anxiety and depression in treatment-naïve cancer patients at the beginning of chemotherapy. Another objective was to explore the associations between emotional distress and quality of life (QoL), an endpoint of great importance in current cancer care.
Abstract: During the previous decades, women with Multiple Sclerosis (MS) were discouraged from having children, as pregnancy was deemed dangerous for pregnancy outcome and a contributing factor for exacerbation of MS. Current knowledge shows that women with MS are no more likely to have pregnancy or delivery complications compared to healthy women. Immunomodulatory therapies should be avoided during pregnancy and while breastfeeding. However, despite that it is still not recommended during pregnancy, Glatiramer acetate has fewer risks than the other MS drugs with respect to pregnancy outcome. IVIg treatment appears to be safe in unblinded studies and may be used after the first trimester to prevent the exacerbation of postpartum relapses. Gestation is a period of decreased risk for a relapse, whereas relapses are more common in the first six months after childbirth, compared to the pre-pregnancy period. Breastfeeding and epidural anaesthesia are not associated with increased incidence of post-partum relapses.
Abstract: The primary aim of this study was to assess whether epoetin alpha (Ea) would improve cognitive performance in a group of anaemic cancer patients receiving chemotherapy. The secondary aim was to confirm the positive impact of Ea on haematological parameters, and quality of life (QOL). Fifty patients with solid tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for 12 weeks and were administered the Mini-Mental State Examination and the European Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior to Ea therapy and at study completion. No clinically significant alterations were observed on cognitive function during Ea treatment. Changes in cognitive function were unrelated to Hb change and there were no significant differences in cognitive performance between Ea responders and non-responders. The analyses revealed clinically significant improvements in Hb levels, physical and role function, and clinically meaningful reductions in fatigue. Hb changes were significantly associated with the magnitude of improvement in QOL parameters. The lack of a clinical benefit in cognition observed in this study during Ea treatment may redirect the focus of research from enhancing to maintaining cognitive function, since stability in cognitive performance through time may be as well clinically important.
Abstract: The co-occurrence of a brain tumour and demyelinating disease of the central nervous system (CNS) constitutes a rare clinical entity. We herein report the incidence of meningioma and CNS non-specific demyelination in a patient with a 6-year history of operated brain tumour (meningioma). Our case bolsters the argument that in at least some cases, the occurrence of a brain tumour could predispose to CNS non-specific demyelination.
Abstract: Bortezomib has demonstrated significant activity in clinical trials, mainly against recurrent or newly diagnosed multiple myeloma (MM). Peripheral neuropathy is a significant toxicity of bortezomib, requiring dose modification and potential changes in the treatment plan when it occurs. The mechanism underlying bortezomib-induced peripheral neuropathy (BIPN) is unknown. Metabolic changes resulting from the accumulation of bortezomib in the dorsal root ganglia cells, mitochondrial-mediated disregulation of Ca(++) homeostasis, and disregulation of neurotrophins may contribute to the pathogenesis of BIPN. It is increasingly recognized that BIPN may be a proteasome inhibitor class effect, producing primarily a small fiber and painful, axonal, sensory distal neuropathy. Incidence of BIPN is mainly related to various risk factors, including cumulative dose and evidence of preexisting neuropathy. Assessment of BIPN is based primarily on neurologic clinical examination and neurophysiologic methods. To date, apart from the use of dose reduction and schedule change algorithm, there is no effective treatment with neuroprotective agents for BIPN. Analgesics, tricyclic antidepressants, anticonvulsants, and vitamin supplements have been used as symptomatic treatment against bortezomib-associated neuropathic pain with some success. This review looks critically at the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of BIPN, and highlights areas for future research.
Abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, especially the G2019S mutation, have been identified as a common cause of Parkinson's disease in southern European and other Mediterranean populations (Iberians, Ashkenazi Jews and North African Arabs). Owing to the geographic and historic vicinity of Greece with areas of high prevalence of LRRK2 mutations we studied the frequency of the G2019S mutation in a well characterized cohort of familial and sporadic Parkinson's disease patients of Greek origin from mainland Greece. The prevalence of the LRRK2 R1441C mutation and the G2385R Asian polymorphism was also determined. We identified no patients with any of the studied mutations/polymorphisms. Very low prevalence of the LRRK2 G2019S mutation has been reported in other southern European populations. LRRK2 mutations appear to be limited in certain populations and differing ancestry and founder effects may explain the reported variability. Accurate estimations of the frequency and penetrance of different LRRK2 mutations are essential for correct and cost-efficient use of genetic testing and proper genetic counseling of patients with Parkinson's disease.
Abstract: We report two patients who developed persistent oculogyric crisis, obsessional thoughts and psychiatric symptoms after prolonged treatment with typical and atypical antipsychotics. Both our patients did not improve after withdrawal of these antipsychotics, but rather after quetiapine was administered.
Abstract: The link between mental health issues and smoking has been an important area of investigation. However, little is known about this association in a general adult, male forensic population. The aim of this study was to identify demographic and clinical (depression and anxiety) variables that predict smoking in a forensic population. A large cohort of 353 inmates in a high-security prison underwent a psychiatric interview, including administration of the Montgomery-Asberg Rating Scale for Depression (MADRS) and Hamilton's Rating Scale for Anxiety (HAM-A). Multiple regression analysis suggested that younger age and higher depression scores might predict the amount of daily smoking in this population. In contrast, anxiety symptoms were not an independent predictor for smoking in our study. These findings support the need for additional research to focus on those factors associated with smoking in forensic populations. Psychiatric screening for younger male individuals in forensic settings and targeted cognitive-behavioral interventions to treat depressed smokers may ameliorate the smoking abstinence rate in prisons.
Abstract: The present study aimed to detect any significant changes of F wave variables associated with acute hemiparesis in a group of stroke patients with relatively preserved consciousness (Glascow Coma Scale (GCS) score 8 or higher) and to detect the possible clinical significance of F wave recording in acute stroke patients for diagnostic purposes.
Abstract: To prospectively detect significant transient F wave abnormalities obtained after exercise in patients with peripheral arterial disease (PAD) and to assess the potential diagnostic sensitivity of dynamic F wave study in such a context.
Abstract: The current prospective study sought to trace the incidence and severity of cisplatin plus paclitaxel (DDP+P)-induced neuropathy and to determine its clinical and electrophysiological pattern. Furthermore, it was attempted to describe its evolution by following up the course of peripheral neuropathy (PN) during chemotherapy as well as 3 months after its discontinuation. Thirteen adult patients scheduled to be treated with six courses of cumulative DDP+P-based regimens for a non-myeloid malignancy participated in this study. These patients were clinically and electrophysiologically monitored at baseline, during chemotherapy and 3 months after its discontinuation. The severity of PN was summarized by means of a modified PN score. Evidence of PN was disclosed in nine of the 13 patients (69.2%). The mean PN score for patients that manifested some grade of PN was 17.3 +/- 6.1 (range 9-28). All longitudinal comparisons concerning the motor conduction velocities (MCV) variables failed to reach significance. By contrast, comparisons of the mean changes at baseline and each of the follow-up studies revealed a significant decrease in all sensory action potentials examined. The follow-up evaluation performed 3 months after the discontinuation of chemotherapy showed that the DDP+P-induced neuropathy persists and progresses over time. Our results indicate that the majority of patients treated with a DDP+P-based regimen at full dose intensities would manifest an axonal, predominately sensory PN, of mild to moderate severity, which would persist for several months after the discontinuation of chemotherapy.
Abstract: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Most cases are sporadic but about 10-15% of patients have a positive family history of PD.
Abstract: The current prospective study sought to trace the incidence and severity of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical and electrophysiological pattern.
Abstract: The current study aimed to assess the viability of sympathetic sudomotor fibers in patients suffering from mild peripheral arterial occlusive disease (PAD).
Abstract: The aim of this study was to evaluate the headache and other neurological symptoms and signs as guide predictors for the occurrence of brain metastases in cancer patients. We prospectively studied 54 cancer patients with newly appeared headache or with a change in the pattern of an existing headache during the recent months. All patients completed a questionnaire regarding headache's clinical characteristics and existence of accompanying symptoms. They also underwent a detailed neurological, ophthalmologic examination and brain neuroimaging investigation. Brain metastases were diagnosed in 29 patients. Univariate regression analysis showed an association between occurrence of brain metastases and nine clinical symptoms or signs. Multivariate regression analyses emerged only four of them as significant independent predictors. These were: bilateral frontal-temporal headache, more pronounced on the side of metastasis in cases of single metastases, with duration > or =8 weeks, pulsating quality and moderate to severe intensity (OR: 11.9; 95% CI. 2.52-56.1), emesis (OR: 10.2; 95% CI. 2.1-55.8), gait instability (OR: 7.4; 95% CI. 1.75-33.9) and extensor plantar response (OR: 12.1; 95% CI. 2.2-120.7). In conclusion, all cancer patients who manifest the above independent clinical predictors should be highly suspected for appearance of brain metastases and therefore should be thoroughly investigated.
Abstract: Approximately 40% of patients with Parkinson's disease (PD) experience symptoms of depression. Our aim was to evaluate the effect of depression on disease severity, motor function and other phenotypic characteristics of PD.
Abstract: The current setting tested the hypothesis that advanced age would be strongly associated with increased incidence and severity of chemotherapy-induced peripheral neuropathy (CIPN).
Abstract: We present a case of herpetic meningoencephalitis confirmed by PCR in a 22-y-old male, with accompanying appearance of a large intracerebral haematoma as a complication. Despite the impressive imaging findings, the final outcome of the patient's progress was favourable.
Abstract: Cases with a clinical and electroencephalographic phenotype of benign epilepsy of childhood with centrotemporal spikes (BECTS) in association with a proven organic brain lesion have rarely been reported. To our knowledge, we herein describe for the first time a patient with Wilson's disease who subsequently manifested BECTS. Our case bolsters the argument that in at least some cases, BECTS is associated with organic brain disease.
Abstract: We conducted a randomized, open-label, controlled trial to assess the efficacy of oxcarbazepine for prophylaxis against oxaliplatin-induced peripheral neuropathy (OxIN). Thirty-two patients with colon cancer received 12 courses of the FOLFOX-4 regimen and were randomly assigned to receive oxcarbazepine (600 mg BID) or chemotherapy without oxcarbazepine. The incidence of OxIN was strikingly decreased in patients receiving oxcarbazepine (31.2% vs 75%). Oxcarbazepine may prevent OxIN symptoms. Further larger placebo-controlled trials are warranted to confirm our results.
Abstract: The aim of this study was to collect normative data for sympathetic skin responses (SSR) elicited by electrical stimulus of the ipsilateral and contralateral peripheral nerves, and by magnetic stimulus of cervical cord. SSRs were measured at the mid-palm of both hands following electrical stimulation of the left median nerve at the wrist and magnetic stimulation at the neck in 40 healthy adult volunteers (mean age 52.2 +/- 12.2 years, 19 males). The onset latency, peak latency, amplitude and area were estimated in "P" type responses (i.e., waveforms with a larger positive, compared to negative, component). SSR onset and peak latency were prolonged when the electrical stimulus was applied at the contralateral side (i.e., the SSR recorded in the right palm P < 0.001). The onset latency was similar on both sides during cervical magnetic stimulation. However, peak latency was faster on the left side (P < 0.03). Comparison of electrical and magnetic stimulation revealed that both the onset and peak latency were shorter with magnetic stimulation (P < 0.001). The latency of a SSR varies depending on what type of stimulation is used and where the stimulus is applied. Electrically generated SSRs have a longer delay and the delay is prolonged at the contralateral side. These factors should be taken into account when interpreting SSR data.
Abstract: The authors sought to identify factors associated with poor compliance with driving restrictions due to a diagnosis of epilepsy. They compared the demographic and clinical characteristics of 60 patients with epilepsy who, despite the authors' recommendation, continued to drive, with those of 60 age- and sex-matched epileptic patients who refrained from driving. The results showed that patients with epilepsy do not comply with driving restrictions, mainly for employment-related reasons.
Abstract: A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN).
Abstract: A randomized, controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy (PIPN). Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy were randomly assigned to receive either chemotherapy with vitamin E (300 mg twice a day, Group I) or chemotherapy without vitamin E supplementation (Group II). A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy. The severity of PIPN was summarized by means of a modified Peripheral Neuropathy (PNP) score. The incidence of neurotoxicity differed significantly between groups, occurring in 3/16 (18.7%) patients assigned to the vitamin E supplementation group and in 10/16 (62.5%) controls (P=0.03). The relative risk (RR) of developing PIPN was significantly higher in controls than in vitamin E group patients (RR=0.3, 95% confidence interval (CI)=0.1-0.9). Mean PNP scores were 2.25+/-5.1 (range 0-15) for patients in Group I and 11+/-11.63 (range 0-32) for those in Group II (P=0.01). Vitamin E supplementation was well tolerated and showed an excellent safety profile. This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage. A double-blind, placebo-controlled trial is needed to confirm these results.
Abstract: We sought to record significant F wave variable changes in ALS patients having no advanced disease. Furthermore, an interpretation of these F wave abnormalities in the context of upper (UMN) and lower motor neuron (LMN) dysfunction was attempted.
Abstract: The authors retrospectively reviewed all neurologic records of an emergency unit from 1999 to 2003 to identify a potential association between lunar phases and seizure occurrence. Overall 859 patients admitted for seizure occurrence were divided into the four quarters of the synodic month according to moon phases. A significant clustering of seizures around the full moon period was observed, supporting the ancient belief of periodic increased seizure frequency during full-moon days.
Abstract: The current study aimed to investigate the impact of carpal tunnel syndrome (CTS) on sympathetic skin response (SSR) recorded from the median and ulnar territory. Thirty patients were studied and idiopathic CTS was documented in a total of 46 hands. These were classified, according to electrophysiological criteria, into two groups; a group of 31 hands with severe CTS and a group of 15 hands with mild/moderate CTS, and were compared with a group of 30 hands of age-matched controls. SSR was recorded simultaneously from the median and ulnar side of the palm following electrical stimulation at the wrist, in a mid-point between median and ulnar nerve. Latency, amplitude, habituation and the median-to-ulnar ratio were estimated. In all controls clear recordings of SSR were obtained. In the patient groups, absence of SSR was never observed either in mild/moderate or in the severe CTS hands. The mean SSR latency and amplitude values recorded from both the median and ulnar nerves did not significantly differ between mild/moderate or severe CTS hands and controls. Likewise, the median-to-ulnar ratio and habituation of SSR latencies and amplitudes did not significantly differ between groups. SSR does not seem to be a sensitive method for evidence of autonomic involvement in CTS, even in patients manifesting sudomotor or other autonomic symptoms. In the present setting, SSR appeared to be independent of somatic afferent function and the corresponding sensory action potentials.
Abstract: Visual hallucinations are common in medication-treated Parkinson's disease (PD) patients. Although their etiology is unknown several factors seem to be involved in their pathogenesis. The aim of this study was to identify possible risk factors and determine clinical characteristics associated with the development of visual hallucinations in PD.
Abstract: To evaluate the epidemiological and clinical features of motor neuron disease (MND) in a region (835,000 inhabitants) of south-western Greece.
Abstract: The authors conducted a pilot, randomized, open label with blind assessment, controlled trial to determine whether vitamin E supplementation has a neuroprotective effect in chemotherapy-induced peripheral nerve damage.
Abstract: The aim of this study was to evaluate the effectiveness and the impact of once-weekly administration of epoetin alfa (Ea) on the management of anaemia and on the quality of life (QOL) of cancer patients receiving chemotherapy. Eighty cancer patients with life expectancy > or = 24 weeks and haemoglobin (Hb) levels < 10.5 g/dL were studied. After an initial screening of patients' demographic and clinical characteristics, Ea 40000 U once a week was administered over a period of 4 months. In case of patients with Hb level exceeding > 14 g/dL or in case of non-response, the dosage was reconsidered. Every month, data regarding Hb levels, clinical variations, changes in the chemotherapy regimen and transfusion use since the last study visit, were evaluated. The Linear Analogue Scale Assessment scale was used for the evaluation of the QOL. The readmissions to hospital rates (P < 0.002) and the transfusion use rates (P < 0.003) were significantly decreased comparatively with baseline. A mean increase from baseline to the final Hb level (P < 0.001) was established, as well as a significant improvement in the functional ability, energy and in the overall QOL (P < 0.001). In conclusion, the treatment of cancer patients with Ea once-weekly is effective and safe, improving their haematological parameters and QOL.
Abstract: The goal of this study was to investigate the potential role of clinical and electrophysiological signs of chemotherapy-induced neurotoxicity (CIPN) in predicting the final outcome of CIPN.
Abstract: To investigate the within 3 days effects of carotid endarterectomy (CEA) on functional status of the central motor system in patients with carotid stenosis by means of transcranial magnetic stimulation (TMS).
Abstract: Neurotoxicity is a common feature of the acute syndrome of systemic snake envenomation. In this report a patient with delayed onset of neurological manifestations after multiple bites of a non-venomous snake is described. The neurological cascade consisted of segmental painful muscle spasms presented several days after the snake bites, which gradually subsided and within a month was followed by muscle weakness in the legs. The latter progressed to flaccid quadriplegia with additional respiratory and autonomic failure leading to death after total disease duration of 5.5 months. The possibility that this unique neurological syndrome of fatal progressive neuropathy could be caused by either tetanus or an immune reaction initiated by snakebites is discussed.
Abstract: The current study intended to determine the incidence, severity and reversibility of paclitaxel plus carboplatin (CP)-induced peripheral neuropathy (CPPN) and to describe its clinical and electrophysiological features.
Abstract: The authors report 2 patients with schizophrenia who developed focal tardive dystonia secondary to treatment with atypical antipsychotics (risperidone, olanzapine). When quetiapine was gradually introduced and other antipsychotics were discontinued, these patients experienced remarkable and sustained improvement of their dystonic symptoms, without loss of psychotic symptom control. The mechanism by which quetiapine may improve tardive dystonia caused by other atypical antipsychotics is unclear. Due to its receptor and pharmacologic profile, quetiapine is the atypical antipsychotic that is most similar to clozapine (without its hematologic side effects), which leads the authors to consider it for the treatment of tardive movement disorders.
Abstract: The current study aimed to assess the viability of sympathetic sudomotor fibers in cancer patients treated with cisplatin or paclitaxel-based chemotherapy and to ascertain whether this method could contribute to the diagnostic sensitivity of conventional techniques. Sympathetic skin response (SSR) from the hand and sole of 23 cancer patients (nine females and 14 males, mean age 62.4 +/- 10.5 years) was recorded unilaterally before and after chemotherapy with six courses of cumulative cisplatin or paclitaxel containing regimens. Clinical and electrophysiological data were also collected and correlated with the SSR results. Twenty-three healthy subjects served as controls. SSR abnormalities were only present in patients with evidence of peripheral neuropathy assessed by conventional nerve conduction techniques. Three patients had absent SSR in the upper limb whilst six patients had absent SSR both in the upper and lower limbs. In the upper limb, the mean SSR latency was not significantly altered through time (P = 0.086). In the lower limb the mean delay from baseline to follow-up was significantly changed (P = 0.029). In patients, the mean SSR latency was significantly prolonged compared with controls in both upper limb (P = 0.001) and lower limb (P = 0.000). SSR abnormalities were strongly related to sensory conduction abnormalities as detected by conventional techniques (r = 0.39, P = 0.004). Our results showed that SSR does not seem to add to the diagnostic sensitivity of conventional techniques in chemotherapy-induced neuropathy. However, its role in the disclosure of small fibers neuropathy abnormalities is worth considering. Further studies are warranted to address this important issue.
Abstract: The aim of the present work was to study the characteristics of motor complications in a group of familial Parkinson's disease (fPD) patients in comparison with matched sporadic PD (sPD) patients. Fifty-one fPD and 51 sPD patients matched for age and disease duration, used as controls, were included in the study. The Unified Parkinson's Disease Rating Scale was completed during clinical examination and all patients were questioned about the characteristics of motor complications. The mean time from start of L-dopa therapy to the onset of motor fluctuations (MF) and L-dopa-induced dyskinesias (LID) as well as the mean time from symptom onset to the development of MF and LID was significantly shorter in the fPD group of patients. An analysis revealed a higher occurrence of MF and LID in fPD patients in the group with disease duration of 5 years or less. FPD may be associated with a higher prevalence and earlier onset of motor complications during the initial stages of the disease. Genetic factors may contribute to the specific characteristics of motor complications in fPD.
Abstract: To record the impact of epilepsy on the psychological health and HRQOL of patients suffering from mild epilepsy in a rural area of southeastern Greece.
Abstract: The authors present a case of paroxetine-induced rabbit syndrome in a 65-year-old white woman. To their knowledge, this is the first report in the literature describing rabbit syndrome induced by the administration of a selective serotonin reuptake inhibitor-specifically, paroxetine in combination with perphenazine and amitriptyline.
Abstract: The clinical severity of late onset Parkinson's disease (PD) varies from patient to patient and it is further complicated by the increasing prevalence of accompanying disorders in the elderly. We set out to study the impact of ischemic heart disease, minor stroke, hypertension and diabetes mellitus in a group of late onset PD patients (age >or=70 years). Consecutive late onset PD patients seen in the Department of Neurology, Medical School of Patras, Greece were included in this study. We used very strict criteria to eliminate the possibility of including patients with vascular parkinsonism. Comparisons were made between groups of patients suffering with idiopathic Parkinson's disease (IPD) and the above-mentioned diseases. One hundred and sixty-seven consecutive late onset PD patients were included in this study. The most common accompanying disorders in our group were hypertension in 31 (18%) of the patients and minor stroke in 20 (12%). The Hoen and Yahr score in late onset IPD patients who suffered from minor stroke, ischemic heart disease or diabetes mellitus was significantly higher when compared with patients without the above disorders. The results clearly suggest that the presence of vascular disease on an IPD patient may aggravate PD severity. In clinical grounds, these findings can be proved significant since early and aggressive prevention of vascular disease and treatment of vascular risk may contribute in controlling symptom severity in PD.
