Morphometric assessments for the prognostic evaluation of human gliomas.

BACKGROUND AND AIM: To correlate stereological parameters to the WHO morphological classification of brain tumours and to address the prognostic value of the different parameters. METHODS AND MATERIALS: A quantitative analysis of 50 astrocytomas was performed by an image analysis system. At least 450 nuclei were counted and measured in every sample. The ANOVA 1-way test and Newman-Keuls modification were used for statistical evaluation. RESULTS: The morphometric data showed significant differences between the tumour grades. We found the nuclear volume and form factor to be parameters of the degree of 'nuclear atypia' from low- to high-grade gliomas. When malignancy was increased, the mean values of nuclear orientation were found to be elevated. CONCLUSIONS: The results of our study underline the usefulness of morphometric techniques in tumour research. These techniques seem to be an important tool for grading gliomas and also for practical therapeutic purposes.

An unusual presentation of neurosyphilis as a probable migraine.

We describe a case which initially presented as persistent and untreatable probable migraine, which was subsequently diagnosed as neurosyphilis during the clinical evaluation. All symptoms regressed after appropriate treatment. We suggest that the possibility of neurosyphilis should be taken into account in the differential diagnosis of a persistent headache which does not respond to medication.

Effects of escitalopram on stress-related relapses in women with multiple sclerosis: an open-label, randomized, controlled, one-year follow-up study.

A growing body of evidence supports the association between Stressful Life Events (SLEs) and increased risk for relapse in Multiple Sclerosis (MS). In this open-label, randomized, controlled, one-year prospective study we investigated the effects of escitalopram on stress-related relapses in 48 women with relapsing-remitting MS. Patients were randomly assigned either to receive escitalopram 10mg/day (e-group, N=24) or to continue with treatment as usual, as a control group (c-group, N=24). SLEs were documented weekly in self-report diaries and were classified afterwards as short- or long-term depending on their psychological impact as this was subjectively felt by the patient. The cumulative risk for relapse was 2.9 times higher for controls than for escitalopram-treated patients (95% CI=1.7-5.1, p<0.001) and it was influenced only by long-term SLEs. In the e-group only 3 or more long-term SLEs were associated with a significant increase of the risk of a relapse during the following 4 weeks, and this risk was 4 times lower compared to the c-group. Our study shows preliminary evidence that escitalopram may constitute an effective and well-tolerated treatment option for the prevention of stress-related relapses in women with MS.

Spinal cavernoma: an unusual cause of acute monoparesis.

INTRODUCTION: Cavernous hemangiomas or cavernomas are uncommon vascular malformations of the central nervous system involving most commonly the cerebral hemispheres where they are detected in young to middle aged adults. We present an unusual case of acute monoparesis caused by an intramedullary cavernoma in a woman of advanced age. CASE REPORT: A 67-year-old woman presented with walking difficulties with acute onset 2 months previously. On neurologic examination, there was a pure right leg monoparesis with moderate spasticity. Tendon reflexes were brisk and there was a Babinski's sign in her right lower limb. The initial diagnosis was lacunar stroke, but the brain magnetic resonance imaging revealed a right temporal cavernoma-obviously not associated with her monoparesis. The consequent spinal MRI revealed an intramedullary lesion at the T1 level, consistent with a cavernoma. CONCLUSION: Our patient presented with an acute monoparesis because of a spinal cavernoma, a most unusual occurrence.

Frequency and causes of early-onset dementia in a tertiary referral center in Athens.

OBJECTIVE: To investigate the frequency and causes of early-onset dementia (EOD) in consecutive patients in a highly specialized dementia referral center, focusing on unusual cases, particularly with early and/or rapid onset, in Athens, Greece. METHODS: Patients referred for dementia diagnosis according to specific referral criteria during a 3 years period. We examined the distribution of patients diagnosis and differences in sex, education, dementia severity, cognitive function, and the duration of disease (from onset to referral) between the EOD (<65 y) and the late-onset dementia (LOD) groups. RESULTS: From a total of 260 consecutive demented patients, there were 114 EOD patients or 44% of all demented patients. No significant differences were observed between the EOD and LOD groups in cognitive or behavioral measures. However, the duration from onset to consultation was significantly longer in the EOD group. Also, in the EOD group, the rates of patients with Alzheimer disease and Parkinson disease dementia were relatively low and the rate of patients with frontotemporal lobar degeneration was relatively high and the proportion of secondary dementias was high. CONCLUSIONS: We conclude that EOD patients are more likely to be seen in specialized settings. The underlying diseases are considerably different in EOD compared with LOD. Secondary causes are often found in patients with EOD. Patients with EOD had an unexpectedly longer time-to-diagnosis than patients with LOD. This argues for a need of better education about the clinical presentation of dementia in the young and middle aged.

Serum uric acid levels in patients with Parkinson's disease: their relationship to treatment and disease duration.

UNLABELLED: There is evidence to support that oxidative stress is increased in Parkinson's disease (PD) and contributes to degeneration of dopaminergic neurons. Uric acid (UA), a natural antioxidant in blood and brain tissue, scavenging superoxide, peroxynitrite and hydroxyl radical, was found reduced in the serum of PD patients. In addition low plasma uric acid (UA) levels have been associated with an increased risk of PD. OBJECTIVES: The aim of our study was to investigate serum UA levels in PD patients compared with age-matched healthy controls and their possible relationship with several clinical parameters of PD and pharmaceutical treatment. PATIENTS AND METHODS: We measured serum UA levels in 43 PD patients and 47 healthy volunteers, age and sex-matched. UA levels were correlated with disease duration, severity and treatment. RESULTS: Low UA levels were observed in PD patients compared with controls (p=0.009). Age, Body Mass Index (BMI) and UPDRS III score did not significantly affect serum UA concentrations, whereas gender was found to contribute significantly to UA level (p<0.000). Strong and significant inverse correlations of UA with disease duration (R(s)=-0.397, p=0.009) and daily levodopa dosage (R(p)=-0.498, p=0.026) were observed. These associations were significant for men (R(s)=-0.441, p=0.04 and R(s)=-0.717, p=0.03 respectively), but not for women (R(s)=-0.221, p=0.337 and R(s)=-0.17, p=0.966 respectively). CONCLUSION: Our results suggest that there may be increased consumption of UA as a scavenger in PD, possibly heightened by dopaminergic drug treatment. Given the antioxidant properties of UA, manipulation of its concentrations should be investigated for potential therapeutic strategies of the disease.

Selective Reminding Test: demographic predictors of performance and normative data for the Greek population.

The Buschke Selective Reminding Test (SRT) measures verbal learning and memory during a multiple-trial list-learning task, which allows for analysis of encoding, storage, and retrieval data. This study of 443 healthy participants (ages 18 to 83 years with 3 to 18 years of education) presents normative data for the Greek population. Statistical analysis indicated that age and educational level were correlated with all the variables as well as sex, although to a considerably lesser extent. Performance on most of the measures decreased with increasing age and lower education, whereas sex differences favored women over men. Based on these results, the sample was stratified into six age groups and three levels of education, with mean and standard deviation for each group. Current norms for the Selective Reminding Test represent a useful neuropsychological tool in clinical practice for patients with memory dysfunction, irrespective of etiology.

Rapidly progressive dementia: causes found in a Greek tertiary referral center in Athens.

Dementia is generally considered as rapidly progressive [rapidly progressive dementia (RPD)], in cases with overt cognitive impairment, established within months. Data about the relative frequency of underlying diseases in cases of RPD are few and extremely variable, depending on the clinical setting. We examined the relative frequency of the underlying causes of RPD, in a university tertiary referral center, in Athens. A series of consecutive patients presenting with RPD in a 3-year period was included. All patients received a comprehensive clinical, imaging, and laboratory evaluation. Of a total of 279 patients hospitalized for dementia diagnosis, 68 patients had RPD (37 males and 31 females). Mean age at onset +/-SD was 65.5+/-10.0. The most common cause of RPD was secondary dementias, accounting for 18 cases (26.5%). Alzheimer disease and frontotemporal dementia were almost equally represented, accounting for 12 (17.6%) and 11 (16.2%) cases, respectively. Vascular dementia, Creutzfeldt-Jakob disease, and various neurodegenerative diseases accounted for 9 cases each (13.2%). In a tertiary referral center, secondary dementias represented the most frequent cause of cases presenting with RPD. As a substantial number of these cases are potentially treatable, our finding reconfirms and underscores the importance of an exhaustive evaluation in any case presenting with RPD.

Familial asymmetric distal upper limb amyotrophy (Hirayama disease): report of a Greek family.

INTRODUCTION: Hirayama disease is a rare nonprogressive, predominantly unilateral, juvenile distal upper limb amyotrophy that involves C7, C8, and Th1 innervated muscles. The etiology and pathogenesis of this focal amyotrophy is presently unknown. There is a debate as to whether Hirayama disease is an unusual neck flexion induced cervical myelopathy or an intrinsic motor neuron disease. Despite being a sporadic disorder, familial forms have been occasionally described, with either autosomal recessive or dominant inheritance. CASE SERIES: We describe a 3-generation Greek family, with 4 members affected by a benign distal upper limb amyotrophy of long duration, reminiscent of Hirayama disease, suggesting an autosomal dominant inheritance pattern. Hypothesizing that this familial amyotrophy might be related to autosomal dominant distal spinal muscular atrophy type V(dSMA-V) that is characterized by prominent involvement of the distal upper extremities, we tested the index case for glycyl tRNA synthetase and Berardinelli-Seip congenital lipodystrophy (BSCL2) N88S and S90L gene mutations (by direct sequencing) that are involved in the development of dSMA-V phenotype. Despite the phenotypical similarity of this familial amyotrophy to dSMA-V, no missense mutation in the genes presently associated with it was detected. CONCLUSION: The reported family is the first in the literature with occurrence of Hirayama amyotrophy in 3 generations of a family. Considering that familial forms of Hirayama amyotrophy are uncommon, it could be assumed that they might represent a different subtype of the same disease having the same clinical features but different pathogenesis.

Epidemiological, clinical and genetic study of familial amyloidotic polyneuropathy in Cyprus.

UNLABELLED: OBJECTIVES. To define the incidence and prevalence of familial amyloidotic polyneuropathy (FAP) TTRVal30Met on the island of Cyprus. To study the clinical phenotype and genetic features of FAP TTRVal30Met in the Cypriot population. METHODS: The clinical and neurogenetic databases were used to identify probands with FAP TTRVal30Met and detailed family trees were constructed. Potential carriers of the mutation were identified from the family trees and assessed clinically and genetically. Transthyretin was completely sequenced in patients and potential carriers. RESULTS: Thirty-six patients carrying the TTRVal30Met mutation (one homozygote) from 22 families were identified. On 1 December 2003 the prevalence of FAP was 3.72/100,000 while the incidence is estimated to be 0.69/100,000 per year. The phenotype observed was characteristic for a length dependent sensorimotor and autonomic neuropathy with neuropathic pain. Mean age of onset was 46 years. Penetrance is estimated to be 28% and positive anticipation in the age of onset is found. CONCLUSION: FAP is relatively prevalent in Cyprus which may be considered as another endemic focus of the disease in Europe. The mean age of onset and penetrance is different from the Portuguese and Swedish populations. Understanding the biological factors that determine these differences could potentially lead to therapeutic advances.

Age-related morphometric characteristics of human skeletal muscle in male subjects.

OBJECTIVE: The purpose of the present study is to investigate the age-related changes in muscle biopsies from the quadriceps femoris in male subjects of different ages. METHODS: A histological and histochemical study was performed on specimens from the quadriceps femoris from 8 males divided into two groups, under 50 and over 70 years of age. The following measurements were performed: a) number of type 1 and 2 fibres, b) diameter of type 1 and 2 fibres, c) percentage of the number and mean diameter of the two types in the interior and the peripheral area of fascicles. RESULTS: The proportion of type 2 fibres decreased significantly with age (p < 0.005), especially in the periphery of the fascicles, but the proportion of type 1 fibres was not significantly changed. The correlation of fibre size with age showed that type 2 fibres decrease in size with age. This finding was more evident in the periphery of the fascicles (p < 0.05). CONCLUSION: We found that type 2 skeletal muscle fibres decreased in size and proportion with increasing age. The existence of these age changes should be taken into account in the interpretation of muscle biopsies of aged individuals.

Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis.

Defective glutamate (Glu) metabolism and glutamate excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Glycine (Gly), the main inhibitory neurotransmitter, has been shown to potentiate excitatory transmission. In the present study, the levels of Glu and Gly in fasting plasma were measured by high performance liquid chromatography (HPLC) in 20 healthy volunteers and in 65 untreated ALS patients. Increased plasma Glu levels were observed in ALS (p=0.05), correlating with longer disease duration (p=0.03, beta=0.34) and male gender (p=0.02). Furthermore, the increase was found only in the spinal subtype of the disease (p=0.03), while in the bulbar subtype, no significant increase was noted. As regards plasma Gly, no difference was observed between patients and controls; however female patients had higher levels than males. The above results are compatible with the "glutamate hypothesis" of ALS and suggest that the spinal and bulbar-onset subtypes of the disease may be biochemically different.

Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis: the effect of riluzole treatment.

OBJECTIVES: Defective glutamate (glu) metabolism and excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Moreover, glycine (gly) has been shown to potentiate excitatory transmission. The "antiglutamatergic" agent riluzole has been shown to prolong survival in ALS. The aim of the study was to investigate a possible effect of riluzole on plasma glu and gly levels, correlating with clinical response to treatment. PATIENTS AND METHODS: Plasma concentrations of glu and gly were measured in 20 healthy volunteers and 22 ALS patients before treatment and after 6 months on riluzole. RESULTS: At baseline, increased plasma glu correlated with spinal onset and male gender whereas gly levels did not differ between patients and controls. No significant change was observed for both amino acids post-treatment, despite a lower rate of disease progression. CONCLUSION: These results suggest that riluzole may affect disease progression without a significant impact on plasma glu and gly levels, possibly indicating different mechanisms of drug action.

Low plasma total cholesterol in patients with Huntington's disease and first-degree relatives.

Recent studies indicate altered cholesterol homeostasis in Huntington's disease (HD) after it was found that cultured human and mice cells expressing mutant huntingtin show reduced mRNA of cholesterol biosynthetic enzymes. Plasma total cholesterol (TC) levels have been connected to degenerative disorders, but data for HD are lacking. We estimated plasma TC in three groups of HD related subjects: (a) patients with overt symptomatology, (b) subjects with expanded CAG repeat number in the Huntington gene before disease onset, and (c) siblings or descendants of HD patients, with normal CAG repeat number. Compared to TC levels of age-matched controls, all three groups had significantly lower plasma TC levels. The expected positive correlation of TC to age, present in the control group, was absent in the whole group or the three subgroups of the HD subjects. TC of the ApoE genotype subgroups showed small, non-significant differences. In the group of patients, TC levels were not related to severity of illness, duration of illness, and presence of depression or dementia in their symptomatology, while lower TC levels were found in patients with psychotic features. The results indicate altered cholesterol homeostasis in members of families with HD patients. Low TC levels have been connected to increased suicide risk in several studies, and high suicidal ideation has been reported in both HD gene carriers and non-carriers. Although low plasma TC levels do not necessarily imply alterations in brain cholesterol levels, a more detailed study of plasma lipids in HD patients and their first-degree relatives, as well as the search for genetic factors regarding cholesterol synthesis and disposition, are warranted.

RANTES levels are elevated in serum and cerebrospinal fluid in patients with amyotrophic lateral sclerosis.

Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells. Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a C-C beta-chemokine with strong chemo-attractant activity for T-lymphocytes and monocytes. We examined serum levels of RANTES in 20 patients with amyotrophic lateral sclerosis (ALS), 14 patients with non-inflammatory neurological disorders (NIND) and 13 control subjects (CTRL) and cerebrospinal fluid (CSF) levels of RANTES in ALS and NIND group patients in order to investigate whether RANTES as index of immune activation is present in ALS patients. Patients with ALS had higher RANTES levels compared with the NIND patients and CTRL subjects (p = 0.005 and p = 0.02, respectively). CSF RANTES levels were also higher compared with the NIND patients (p = 0.007). No correlation of serum and CSF RANTES levels with disease duration was found. These results may suggest an activated microglia induced recruitment of peripheral inflammatory cells to sites of inflammation in ALS patients.

Circulating interleukin-15 in dementia disorders.

The objective of this study was to assess the role of interleukin-15 (IL-15) as a potential marker of immune reactions in patients with Alzheimer's disease and vascular dementia. The authors measured by immunoassay serum IL-15 levels in 20 patients with Alzheimer's disease and 15 patients with vascular dementia and compared them with serum IL-15 levels in 15 healthy subjects. The authors also studied the effect of treatment with acetylcholinesterase inhibitors (AChEI) on serum IL-15 levels. Patients with Alzheimer's disease were found to have significantly lower serum IL-15 levels compared with healthy subjects and patients with vascular dementia. Healthy subjects and patients with vascular dementia did not differ between each other. Age, sex, disease duration, and Mini-Mental State Examination score did not affect IL-15 levels in any of the groups. Treatment with AChEI had no influence on IL-15 concentrations. The findings suggest that IL-15 is not implicated in the pathogenetic mechanisms of Alzheimer's disease and vascular dementia. An immune hyporesponsiveness at some point during disease development may be responsible for the lower levels of IL-15 and other cytokines in Alzheimer's disease patients.

Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study.

BACKGROUND AND PURPOSE: A simple score derived in the Oxfordshire Community Stroke Project (ABCD score) was able to identify individuals at high early risk of stroke after a transient ischemic attack (TIA) both in a population-based and a hospital-referred clinic cohort. We aimed to further validate the former score in a cohort of hospitalized TIA patients. METHODS: We retrospectively reviewed the emergency room and hospital records of consecutive patients hospitalized in our neurological department with a definite TIA according to the World Health Organization (WHO) criteria during a 5-year period. The 6-point ABCD score (age [<60 years=0, > or =60 years=1]; blood pressure [systolic < or =140 mm Hg and diastolic < or =90 mm Hg=0, systolic >140 mm Hg and/or diastolic >90 mm Hg=1]; clinical features [unilateral weakness=2, speech disturbance without weakness=1, other symptom=0]; duration of symptoms [<10 minutes=0, 10 to 59 minutes=1, > or =60 minutes=2]) was used to stratify the 30-day stroke risk. RESULTS: The 30-day risk of stroke in the present case series (n=226) was 9.7% (95% CI, 5.8% to 13.6%). The ABCD score was highly predictive of 30-day risk of stroke (ABCD=0 to 2: 0%, ABCD=3: 3.5% [95% CI, 0% to 8.2%], ABCD=4: 7.6% [95% CI, 1.2% to 14.0%], ABCD=5: 21.3% [95% CI, 10.4% to 33.0%], ABCD=6: 31.3% [95% CI, 8.6% to 54.0%]; log-rank test=23.09; df=6; P=0.0008; P for linear trend across the ABCD score levels <0.00001). After adjustment for stroke risk factors, history of previous TIA, medication use before the index TIA, and secondary prevention treatment strategies, an ABCD score of 5 to 6 was independently (P<0.001) associated with an 8-fold greater 30-day risk of stroke (hazard ratio, 8.01; 95% CI, 3.21 to 19.98). CONCLUSIONS: Our findings validate the predictive value of the ABCD score in identifying hospitalized TIA patients with a high risk of early stroke and provide further evidence for its potential applicability in clinical practice.

Add-on lamotrigine treatment and plasma glutamate levels in epilepsy: relation to treatment response.

We investigated the effects of add-on lamotrigine treatment on plasma glutamate (Glu) levels, in 29 epileptic patients. Plasma Glu levels were determined by high-performance liquid chromatography at baseline and at 1 and 3 months post-treatment. In patients with a seizure reduction of > or = 66% a decrease of Glu at month 1 was noted, followed by return to baseline levels at month 3. In the remaining patients a gradual increase of Glu was noted throughout the 3 months of the study. The above findings indicate that an excellent clinical response to add-on lamotrigine may be characterized by a statistically significant, yet transient decrease of plasma Glu levels, while increasing Glu levels may accompany a response that is moderate at best. The combination of lamotrigine with valproate was more frequent in patients with excellent clinical response and tended to result in glutamate decrease.

Common carotid artery intima-media thickness and the risk of stroke recurrence.

BACKGROUND AND PURPOSE: Increased common carotid artery intima-media thickness (CCA-IMT) has been associated with an increased risk of myocardial infarction and stroke. We investigated the relationship between CCA-IMT and recurrent stroke in a cohort of ischemic stroke patients. METHODS: High-resolution B-mode ultrasonographic measurements of the CCA-IMT were performed in a consecutive series of 238 patients hospitalized in our institution with first-ever ischemic stroke. Stroke risk factors and secondary prevention therapies were documented. Patients were followed-up prospectively and the outcome event of interest was recurrent stroke. RESULTS: During a mean follow-up period of 28.9 months (range: 6 to 60 months), 27 recurrent strokes were documented. Patients who experienced recurrent cerebrovascular events had significantly (P=0.005) higher CCA-IMT values (1.01 mm, 95% CI:0.92 to 1.11 mm) than subjects who were free of stroke recurrence (0.88 mm, 95% CI:0.85 to 0.91 mm). After adjustment for baseline characteristics, risk factors and stroke subtypes and secondary prevention therapies increasing CCA-IMT was found to be an independent predictor of stroke recurrence. For each increment of 0.1 mm in CCA-IMT the probability of experiencing recurrent stroke increased by 18.0% (95% CI:2.0% to 36.0%, P=0.027). CONCLUSIONS: Increased CCA-IMT values are associated with a higher risk of long-term stroke recurrence.