Aristidis Kazis

Long-term results of stem cell transplantation for MS A single-center experience

Objective: To report long-term results of a phase I/II study conducted in a single center in order to investigate the effect of hemopoietic stem cell transplantation (HSCT) in the treatment of multiple sclerosis (MS). Methods: Clinical and MRI outcomes of 35 patients with aggressive MS treated with HSCT are reported after a median follow-up period of 11 (range 2–15) years. Results: Disease progression-free survival (PFS) at 15 years is 44% for patients with active CNS disease and 10% for those without (p = 0.01); median time to progression was 11 (95% confidence interval 0–22) and 2 (0–6) years. Improvements by 0.5–5.5 (median 1) Expanded Disability Status Scale (EDSS) points were observed in 16 cases lasting for a median of 2 years. In 9 of these patients, EDSS scores did not progress above baseline scores. Two patients died, at 2 months and 2.5 years, from transplant-related complications. Gadolinium-enhancing lesions were significantly reduced after mobilization but were maximally and persistently diminished post-HSCT. Conclusion: HSCT is not a therapy for the general population of patients with MS but should be reserved for aggressive cases, still in the inflammatory phase of the disease, and for the malignant form, in which it can be life-saving. HSCT has an impressive and sustained effect in suppressing disease activity on MRI. Classification of evidence: This study provides Class IV evidence that HSCT results in PFS rates of 25%. PFS rate was significantly better in patients with active MRI lesions; HSCT also resulted in a significant reduction in the number and volume of gadolinium-enhancing lesions on MRI.

Prevalence and incidence of Alzheimers disease and other dementing disorders in Pylea, Greece

We investigated the prevalence and incidence of dementing disorders in the city of Pylea, Greece, using a door-to-door three-phase approach, and explored the relationship between age and gender. From the initial cohort of 704-subjects, 112-subjects (15.9 percent) were excluded because they had moved out of town or could not be traced, 102-subjects (14.4 percent) died before the time of actual contact, and 110-subjects (15.6 percent) refused to be contacted. We were able to visit and examine 380-subjects (54 percent); each of them were administered the MMSE by one of three nurses and the CAMCOG by one of three physicians. We selected January 1, 1993, as the study prevalence day. Using specified diagnostic criteria, NINCDS-ADRDA and DSMIIIR, the study neurologists extensively investigated 118 from 380-subjects, who screened positive on MMSE (MMSE < 23) and CAMCOG (< 65). We found 35-subjects affected by dementia, 20 had Alzheimers disease (AD), 11 had vascular or mixed dementia and four had secondary dementia (one Parkinsons disease, one Vitamin B12 deficiency, and two had Tumors). The estimated annual incidence rate for all forms of dementia, after correction for ageing of the samples was 57/1,000 persons aged > 70, made up of dementia of Alzheimer type (39.9/1,000), vascular dementia (13.9/1,000) and other forms (3.5/1,000). The prevalence of both dementia and AD increased steeply with advancing age and was consistently higher in women. The incidence of dementia increases with age, even in the oldest age groups and women have a higher risk of developing dementia than men. AD was the most common type of dementia. Our prevalence and incidence figures for dementia and AD are almost similar to those previously reported in Europe, the United States and Canada.

Neuroacanthocytosis presenting with epilepsy

Sirs: Neuroacanthocytosis, sometimes referred to as chorea-acanthocytosis or Levine-Critchley syndrome, is a rare neurodegenerative disease of unknown aetiology. Following its initial description in 1967 [2], several familial and sporadic cases have been reported, especially in Japan. The clinical picture comprises a variety of involuntary movements including orofacial dyskinesia, choreic movements of the limbs, self-mutilating tongue or lip biting and tics. Other clinical features include intellectual impairment, psychiatric symptoms, personality changes, epileptic seizures and axonal sensorimotor polyneuropathy. Patients have elevated serum creatine kinase levels and acanthocytosis with normal lipoproteins. Epileptic seizures occur late in the course of the disease. It is extremely rare for them to precede the typical symptoms, and in such cases there is difficulty in diagnosis which may delay the correct diagnosis considerably. In this case report, we describe a patient with neuroacanthocytosis who presented with epileptic seizures 4 months before the appearance of the characteristic features of the disease. A male patient, aged 33 years, with an unrelated medical and family history first suffered a generalized tonic-clonic seizure in December 1991, rapidly followed by status epilepticus. Neurological examination was normal and CT of the brain showed no abnormality. The patient was started on 300 mg/day phenytoin. In January 1992, during an epileptic seizure, he suffered a serious head injury, resulting in fracture of the left frontal bone and contusion of the left frontal pole. He was treated conservatively. In March 1992, generalized choreic movements and orofacial dyskinesias began. Because of frequent partial secondarily generalized epileptic seizures, the phenytoin dosage was increased to 600 mg/day without satisfactory effect. In March 1993, the patient was admitted to the C Department of Neurology for further investigation. On examination he was impulsive and distractable. His speech was interrupted by marked orofaciolingual dyskinesias, facial tics and repetitive grunts, sniffs and involuntary vocalization. Generalized choreic movements were noted (Fig. 1) which could be suppressed voluntarily by muscle contraction and during simple mathematical tasks. Retinitis pigmentosa, nystagmus and Kayser-Fleischer rings were absent. There was drooling of saliva

Simultaneous Determination of Dextromethorphan and Dextrorphan in Human Plasma, Urine and Cerebrospinal Fluid by HPLC with Fluorescence Detection

Abstract Dextromethorphan is a non-narcotic antitussive drug that recently attracted interest because of its anticonvulsant and neuroprotective properties. Dextromethorphan undergoes polymorphic oxidation and 5–10% of human subjects are characterised as poor metabolizers on the basis of the formation rate of its O-demethylated metabolite, dextrorphan catalysed by isozyme CYP2D6. A sensitive, selective and reliable high performance liquid chromatographic (HPLC) method for the simultaneous determination of dextromethorphan and dextrorphan in human plasma, urine, and cerebrospinal fluid, is described, using levallorphan as the internal standard. The analytes were extracted from biological fluids by a liquid-liquid extraction procedure. The chromatographic separation was performed on a 5-μm cyano analytical column (220 × 4.6 mm) using a mixture of acetonitrile/distilled water/n-octylamine (19/80.95/0.05, v/v) pH 2.8 as the mobile phase with a flow rate of 1.0 mL/min at 40°C and the chromatographic peaks were ...

P37.7 The effects of imipenem, a GABA-A receptor antagonist, on silent period to transcranial magnetic stimulation

period times (CSP) were measured with single stimulus transcranial magnetic stimulation (TMS). After TMS studies, second EEG recordings were performed within an hour. Results: No seizures were recorded in or afterwards the study, there were no statistically significant difference between the first and second EEG recordings. (Kappa measure of agreement %84) MT values of JME patients were higher than asymptomatic brothers/sisters and healthy individuals. (p 0.0, p 0.0) CSP of JME patients were longer than healthy individuals with statistically significant difference. (p 0.37) CSP of asymptomatic brothers/sisters were also longer than healthy individuals without any statistical difference (p 0.71). Discussion: Higher MT values in JME patients were thought to be related to the anti-epileptic drug therapies. Longer CSP times in JME patients can be explained by the increased excitability of the cortical inhibitory neurons. CSP times in brothers/sisters were also found elongated without any statisticaly significant difference. This can also be explained with the same mechanism.

Correlations of memory performance with clinical profile in patients with Parkinson's disease

Results Pearsons correlation analysis between total score of MMSE and clinical symptoms indicated correlations between MMSE and age [r = -0.479, n = 26, p < 0.05], MMSE and education [r = 0.531, n = 26, p < 0.01], and also between EMQ and illness duration [r = 0.391, n = 26, p < 0.05]. In addition, significant correlations were found between WMS and clinical profile, and more specifically between digit span and age [r = -0.422, n = 26, p < 0.05], digit span and education [r = 0.591, n = 26, p < 0.01], visual reconstruction and age [r = -0.477, n = 25, p < 0.05], visual reconstruction and education [r = 0.566, n = 25, p < 0.01], new learning and age [r = -0.620, n = 26, p < 0.01], new learning and education [r = 0.806, n = 26, p < 0.01]. Finally, Pearsons correlation analysis between total score of MMSE and WMS indicated correlations between MMSE and orientation [r = 0.473, n = 26, p < 0.05], MMSE and mental control [r = 0.535, n = 26, p < 0.01], MMSE and digit span [r = 0.424, n = 26, p < 0.05], MMSE and visual reconstruction [r = 0.421, n = 25, p < 0.05] and MMSE and new learning [r = 0.503, n = 26, p < 0.01].

Lorazepam effects on silent period and corticomotor excitability

Materials and methods Twelve healthy male subjects (median age 35 years) were studied at baseline, following i.v. lorazepam administration and after reversal of the benzodiazepine effects with i.v. flumazenil. Lorazepam was given at a low-dose in one subject (0.0225 mg/kg bolus + 2 μg/kg/h infusion) and at a high-dose (0.045 mg/kg bolus + 2.6 μg/kg/h infusion) in the rest. Threshold (Thr) was measured at 1% steps. SPs were investigated with two complementary methods. First, SPs were elicited using a wide range of stimulus intensities (SIs) (from 5 to 100% maximum SI at 5% increments). At each SI, 4 SPs were obtained and the average value of SP duration was used to construct a stimulus/ response (S/R) curve of SI vs. SP. The resulting S/R curves were then fitted to a Boltzman function, the best-fit values of which were statistically compared for each experimental condition (i.e., baseline vs. lorazepam vs. flumazenil). Second, a large number of SPs was elicited during the three experimental conditions using blocks of 4 stimuli with an intensity alternating between MT and 200% MT. This method was employed so as to reveal the dynamic, time-varying effects of lorazepam and flumazenil on SP duration at two stimulus intensity (SI) levels. Finally, active MEP recruitment curves were constructed and fitted to a Boltzman function the best-fit values of which were statistically compared for each experimental condition.

Autobiographical memory in multiple sclerosis

Materials and methods Eighteen patients with clinically definite multiple sclerosis (6 males and 12 females, with a mean of 41 years of age and 11.3 years of education) were compared to sixteen healthy, age and education matched, controls (6 males and 10 females, with a mean of 36.1 years of age and 13.2 years of education). Autobiographical memory was assessed by the Autobiographical Memory Interview, which measures personal semantic and episodic memories from different time periods – childhood, early adulthood and the recent past – permitting examination of the possible differential effects of brain damage on these two types of autobiographical memory. All statistical analyses were carried out using SPSS.

The paced auditory serial addition test in multiple sclerosis patients: the effect of brain atrophy and T1 lesion load

Background The Paced Auditory Serial Addition Test (PASAT) is being increasingly used as a psychometric tool particularly as a part of the Multiple Sclerosis Functional Composite Measure. Previous studies reported the relationship between T2 lesion load on brain MRI and PASAT scores. The effect, however, of T1 hypointense lesions, which are thought to reflect destructive aspects of the disease process, and brain atrophy remains unexplored.

The Alzheimer's patients ... do learn!

Background Cognitive disorders are of the main deficits in the first stages of dementia of Alzheimers type (DAT). Memory deficits are obviously as DAT patients delete almost immediately new information and have encode and recall processing impairment. Basing on the new scientific data for neuroplasticity and neurogenesis of the elderly brain we used a memory intervention program in order to help mild DAT patients to improve their mental state.