Co-occurrence of brain tumours and demyelination of the central nervous system: coincidence or interrelation?

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.

7-Bromoindirubin-3'-oxime induces caspase-independent cell death.

Indirubin, an isomer of indigo, is a reported inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) as well as an agonist of the aryl hydrocarbon receptor (AhR). Indirubin is the active ingredient of a traditional Chinese medicinal recipe used against chronic myelocytic leukemia. Numerous indirubin analogs have been synthesized to optimize this promising kinase inhibitor scaffold. We report here on the cellular effects of 7-bromoindirubin-3'-oxime (7BIO). In contrast to its 5-bromo- and 6-bromo- isomers, and to indirubin-3'-oxime, 7BIO has only a marginal inhibitory activity towards CDKs and GSK-3. Unexpectedly, 7BIO triggers a rapid cell death process distinct from apoptosis. 7-Bromoindirubin-3'-oxime induces the appearance of large pycnotic nuclei, without classical features of apoptosis such as chromatin condensation and nuclear fragmentation. 7-Bromoindirubin-3'-oxime-induced cell death is not accompanied by cytochrome c release neither by any measurable effector caspase activation. Furthermore, the death process is not altered either by the presence of Q-VD-OPh, a broad-spectrum caspase inhibitor, or the overexpression of Bcl-2 and Bcl-XL proteins. Neither AhR nor p53 is required during 7BIO-induced cell death. Thus, in contrast to previously described indirubins, 7BIO triggers the activation of non-apoptotic cell death, possibly through necroptosis or autophagy. Although their molecular targets remain to be identified, 7-substituted indirubins may constitute a new class of potential antitumor compounds that would retain their activity in cells refractory to apoptosis.

Peripheral large nerve fibre function in patients with chronic plaque psoriasis.

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.

Effects of carotid endarterectomy on motor evoked potentials elicited by transcranial magnetic stimulation.

PURPOSE: 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). PATIENTS AND METHOD: We studied 30 consecutive patients, 20 males and 10 females with a mean age of 69.2+/-7.1 years, who underwent CEA for symptomatic carotid stenosis. All patients had suffered an ischemic attack 6 months prior to the operation. Two TMS studies, one before and one shortly after CEA were performed on both sides in each of the patients. Resting motor threshold, motor evoked potentials (MEP) amplitude at rest, MEP latency at rest and during contraction and silent period duration (SPD) were recorded and analyzed. Two groups of data were collected. Group 1 consisted of data from the operated side in all 30 patients. Group 2 consisted of data from the contralateral side and served as a control. RESULTS: Motor resting thresholds were similar in the two groups. Intragroup pre and post CEA comparisons showed no difference in the operated group and significant increased threshold after CEA on the non-operated side. There was no significant difference of TMS intensity for maximal MEP in either side before or after CEA. Latency at rest and during voluntary contraction and amplitude at rest showed no significant differences between or within groups' comparisons. In group 1 SPD showed a statistically significant increase after CEA as opposed to baseline. In group 2 SPD showed a non significant increase after CEA. CONCLUSION: In the absence of other MEP changes, our finding of prolonged SPD post-operatively suggests preferential influence of the inhibitory cortical circuits. The potential favorable effect of CEA in patients with hyperexcitability such as disabling spasticity after stroke should be further studied.

Add-on topiramate in the treatment of refractory partial-onset epilepsy: clinical experience of outpatient epilepsy clinics from 11 general hospitals.

An open, prospective, observational study was performed to assess efficacy and adverse-event profile of topiramate as add-on therapy in epilepsy. Outpatient neurology clinics from 11 general hospitals in Greece participated in the study. In total, 211 patients with treatment resistant partial-onset seizures who met the inclusion criteria, were studied. After baseline evaluation, topiramate was given at a target dose of 200mg/day over a 1-month titration period. In the subsequent maintenance period, the topiramate dose could be varied according to the clinical results. Patients were followed for in total 6 months, with monthly visits and regular physical, neurological and laboratory examinations. Seizure frequencies decreased to 35--40% of baseline values following 3 months of treatment and remained relatively constant thereafter. The average monthly seizure frequency over the 6-month study period was 4.61, compared to 9.21 at baseline. The number of responders (patients with at least 50% reduction in seizure frequency) followed a similar pattern, i.e., increase during the first 3 months levelling off at a final 80--85% response rate. Of those completing the study, 30% had been seizure-free for at least 3 months and 12% for 5 months. Topiramate was well tolerated, no deviations in laboratory values were found. Adverse events appeared to occur less frequently, and antiepileptic effects were more pronounced in this prospective open-label study than in earlier reports from randomised controlled trials. The nature of the patient population and the application of individualised dose optimisation are proposed as contributing factors to explain the favourable results of this study.

Quantitative evaluation of magnetic resonance imaging (MRI) abnormalities in subclinical hepatic encephalopathy.

BACKGROUND/AIMS: Cirrhotic patients often demonstrate high signal intensity on T1-weighted magnetic resonance (MRI) images in basal ganglia with accumulation of manganese being the predominant causing factor. In these patients, electrophysiological tests and especially electroencephalogram (EEG) are considered to be the most sensitive methods in detection of subclinical hepatic encephalopathy. The aim of this study is to correlate MRI findings with biochemical parameters and EEG alterations in cirrhotic patients without clinically overt encephalopathy. METHODOLOGY: Twenty-two cirrhotic patients (16 males and 6 females, mean age of 65.2 +/- 9.5 years), classified according to Child-Pugh score, were submitted to brain MRI, neurological assessment (including psychometric tests and EEG) and complete biochemical testing. None of them had any clinical signs of brain dysfunction. MRI findings were evaluated both qualitatively (normal, mild, moderate and severe) and quantitatively with the ROI method. EEG alterations were also classified as normal, mild, moderate and severe. RESULTS: Statistical analysis revealed a significant linear association between EEG grading and MRI signal intensity (r2=0.248, p=0.035). Among clinical and biochemical parameters, overall Child-Pugh score and albumin levels were identified as significant predictors of the MRI signal intensity (p=0.006 and p=0.021 respectively). CONCLUSIONS: Although further investigation must be performed to confirm the clinical impact of brain MRI in hepatic cirrhosis, our study strongly suggests that MRI alterations are good predictors of liver and brain dysfunction in cirrhotic patients.

Family history of stroke in stroke types and subtypes.

Many studies have provided data showing that family history of stroke (FHS) is associated with an increased risk of stroke. The association of the FHS with the various stroke subtypes has not been adequately studied. The purpose of this study was to assess the association of the FHS with the two major stroke types (cerebral haematomas and ischaemic strokes) and the four stroke subtypes (cardioembolic, large artery disease, small artery disease, and undetermined) in a Greek population. The FHS was obtained from 421 consecutive acute stroke patients and from 239 matched control subjects. Positive FHS was observed in 49% of all stroke patients compared with 28% of the control subjects [adjusted OR=2.06 (95% confidence intervals (CI) 1.42-3.00)]. Haematomas, ischaemic strokes, and from the ischaemic strokes, both large and small artery disease strokes were strongly associated with positive FHS compared with the control subjects [adjusted OR=2.06 (95% CI 9-3.04), 2.07 (95% CI 1.09-3.91), 2.05 (95% CI 1.24-3.38), and 2.76 (95% CI 1.55-4.91), respectively]. There was no difference between maternal and paternal heritable contribution.In conclusion, FHS was found in this study to be an independent risk factor for all strokes combined, for each stroke type, and for the large and small-artery disease stroke subtypes, but not for the cardioembolic and undetermined stroke subtypes.

Dynamic F wave study in patients suffering from peripheral arterial occlusive disease.

OBJECTIVE: 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. PATIENTS AND METHODS: A series of 40 electrical stimuli were delivered to the peroneal and the posterior tibial nerves of 25 patients with PAD in order to obtain F waves at rest and post-exercise. The following variables were estimated and the obtained pre- and post-exercise data were compared: F persistence, F wave latency, amplitude, duration and F chronodispersion. For each nerve studied, the minimum, average and maximum values were calculated. Conventional electrophysiological data were also collected pre- and post-exercise and the data obtained were also compared. Twenty-five healthy age-, gender- and height-matched individuals served as controls. RESULTS: No evidence of conventional nerve conduction abnormalities was recorded either pre- or post-exercise in the group of patients. As regards the peroneal nerve, the significantly reduced F wave persistence (P = 0.007) and maximum F wave amplitude post- as opposed to pre-exercise (P = 0.05)- were the main findings to emerge. The average (P = 0.017) and the minimum duration (P = 0.005) of tibial F waves were also significantly increased post- compared with pre-exercise. Insignificant differences were observed between pre- and post-exercise neurophysiological and F wave values in the group of controls. CONCLUSION: Given the observed absence of conventional neurophysiological abnormalities, the detection of dynamic F wave changes supports the view of an increased diagnostic sensitivity of this method in patients with mild PAD.

Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy.

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.

The significance of intact sympathetic skin responses in carpal tunnel syndrome.

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.

Factors associated with poor compliance of patients with epilepsy driving restrictions.

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.

Lunar phases and seizure occurrence: just an ancient legend?

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.

Headache characteristics and brain metastases prediction in cancer patients.

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.

Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy.

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.

Clinical and epidemiological features of motor neuron disease in south-western Greece.

OBJECTIVE: To evaluate the epidemiological and clinical features of motor neuron disease (MND) in a region (835,000 inhabitants) of south-western Greece. PATIENTS AND METHODS: The medical records of all patients diagnosed with adult-onset MND at the Department of Neurology of the University Hospital of Patras from 1990 to 2003 were reviewed. RESULTS: Overall 133 patients were identified, corresponding to a mean annual incidence rate of 1.13/100,000 population with male preponderance. Eighty-five of them were males (63.9%) and 48 (36.1%) females with a mean age of 61.4 +/- 13.3 years. The most common type of MND was amyotrophic lateral sclerosis (ALS) being identified in 111 (83.5%) patients, whereas 19 cases (14.3%) were classified as progressive spinal muscular atrophy (PSMA) and three (2.2%) cases as progressive bulbar palsy (PBP). The mean age at onset was 60.3 +/- 13.5 years, while the mean delay between age at onset and age at diagnosis was 1.3 +/- 1.1 years. The symptoms at onset involved the lower limbs in 76 (57.2%) cases, upper limbs in 32 (24%) cases, bulbar region in 22 (16.5%) cases and respiratory muscles in three (2.3%) cases. The mean survival time after onset of disease was 20.4 +/- 8.3 months for ALS patients, 15.3 +/- 4.5 months for PBP and 38.1 +/- 26.4 months for PSMA patients. CONCLUSIONS: There was no statistically significant difference in the results of the considered epidemiological parameters of our study to those reported by other similar studies. The study of the patients with MND showed a predominance of ALS patients. No potentially causative clinical associations were found and no relation between socioeconomic factors, occupational exposure and the disease was noted.

The impact of paclitaxel or cisplatin-based chemotherapy on sympathetic skin response: a prospective study.

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.

A registry-based, case-control investigation of Parkinson's disease with and without cognitive impairment.

In approximately 40% of the patients, Parkinson's disease (PD) is complicated by cognitive impairment. The objective of this study was to evaluate the impact of cognitive impairment on disease severity and motor function in idiopathic PD patients. Forty-one PD patients with cognitive impairment (PD-CI) (Mini-Mental State Examination < or =24) and 41 PD patients without cognitive impairment (PD-Control) matched for age at onset and duration of the disease were examined using the Unified Parkinson's Disease Rating Scale (UPDRS). PD patients with cognitive impairment had overall poorer motor function, worse rigidity (both axial and limb) and bradykinesia, as well as worse performance in activities of daily living compared with matched PD patients without cognitive impairment. This could either be attributed to a direct effect of cognitive impairment on parkinsonian symptoms or to decreased compliance of patients during clinical examination. PD patients should be routinely and carefully screened for dementia and caregivers should be aware of the effect of dementia on PD.