Demetris Vassilopoulos

Cognitive impairment in different MS subtypes and clinically isolated syndromes

OBJECTIVE To investigate the pattern of cognitive impairment in patients with relapsing-remitting (RR), secondary progressive (SP), primary progressive (PP) multiple sclerosis, and patients with clinically isolated syndrome (CIS) suggestive of MS, relative to control participants in the Greek population. METHODS RR patients (N=75), SP patients (N=29), PP patients (N=23), CIS patients (N=33), and healthy control participants (N=43) were assessed by the Brief Repeatable Battery of Neuropsychological Tests (BRBN). RESULTS The overall prevalence of cognitive dysfunction in our patients was 52.8% with CIS patients excluded and 47.5% with CIS patients included. All MS patients differed significantly from controls in all BRBN measures. Similar was the pattern of cognitive dysfunction in patients with CIS suggestive of MS, although verbal learning/memory capacity (as measured by the Selective Reminding Test) remained relatively spared. The comparisons between patient groups revealed some differences in the performance mainly in favor of CIS and RRMS patients. These differences largely disappeared after controlling for physical disability (EDSS). CONCLUSION All MS subtypes patients exhibit a pattern of cognitive impairment running across the studied cognitive domains. The pattern of cognitive dysfunction in patients with CIS is similar with relative sparing of verbal learning.

Episodes of generalized weakness in two sibs with the C164T mutation of the connexin 32 gene

Two sibs with Charcot–Marie–Tooth disease had repeated episodes of generalized weakness. The patients had distal weakness and atrophy as well as findings of CNS involvement on brain MRI. Both patients bear the C164T mutation of the connexin 32 gene but no mutations of the genes responsible for hyper- or hypokalemic periodic paralysis. It is possible that both patients have one disease with complex phenotype due to abnormal expression of the connexin 32 gene.

Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration.

BackgroundCerebrospinal fluid (CSF) biomarkers have been increasingly studied in dementia clinical and differential diagnosis. MethodsWe assessed levels of total tau protein (τT), tau phosphorylated at threonine 181 (τP-181), and β-amyloid1-42 (Aβ42) in 34 patients with frontotemporal lobar degeneration (FTLD), 76 Alzheimer disease (AD) cases, and 93 controls (CTRL). Double sandwich enzyme-linked immunosorbent assays (Innogenetics) were used for measurements. ResultsTotal τ was significantly increased and Aβ42 decreased in FTLD and AD patients as compared with CTRL. CSF τP-181 levels were significantly increased only in AD. The τT/Aβ42 ratio successfully discriminated FTLD from CTRL with a 86.7% specificity and 80.6% sensitivity, whereas the τT alone was more specific (95.7%) but less sensitive (64.75%). For the discrimination of FTLD from AD, τT/Aβ42 ratio was better (90.3% sensitivity and 64.5% specificity) compared with the other biomarkers alone or in combination, whereas τP-181 was less sensitive but more specific (68.4% and 85.7%, respectively). Subtype analysis revealed that the most AD-like profile of biomarkers were observed in FTLD with motor neuron signs, whereas the most non-AD profile were observed in patients with primary progressive aphasia. ConclusionsCombined analysis of CSF biomarkers may be useful for the best possible antemortem discrimination of FTLD from AD.

Impact of the time rate of blood pressure variation on left ventricular mass

Objectives Blood pressure (BP) changes are steeper in hypertensive than in normotensive individuals, whereas an increased rate of BP fluctuations is associated with medial hypertrophy of the carotid arteries. We evaluated the association between the rate of BP variation derived from ambulatory blood pressure monitoring (ABPM) data analysis and left ventricular mass (LVM). Methods ABPM and echocardiographic measurements of LVM were performed in 365 normotensive, 185 white-coat hypertensive (WCH) and 448 uncomplicated hypertensive individuals. Results The daytime and night-time rate of systolic blood pressure (SBP) and diastolic BP variation were significantly higher in hypertensive than in normotensive (P < 0.001) and WCH (P < 0.05) individuals. In the entire study population multiple linear regression models revealed independent determinants of LVM in the following rank order: body mass index (β + 0.266, P < 0.001), daytime SBP (β + 0.264, P < 0.001), male sex (β +0.220, P < 0.001), age (β + 0.203, P < 0.001), daytime heart rate (HR; β − 0.191, P < 0.001), daytime rate of SBP variation (β + 0.167, P < 0.001), and SBP dipping (β − 0.132, P < 0.001). A 0.1 mmHg/min increase in the daytime rate of SBP variation correlated with an increment of 7.087 g (95% confidence interval 4.775–9.399) in the LVM. The addition of the daytime rate of SBP variation in the multiple regression model for the prediction of LVM significantly increased the adjusted model R2 [R2 change 0.024 (2.4%); P for change < 0.001]. Conclusion Steeper BP variations may produce a greater stress on the left ventricular wall and may have an additive role to body habitus, BP and HR levels in the detection of cardiac hypertrophy. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP oscillations.

Symptomatic focal mononeuropathies in diabetic patients: increased or not?

Abstract The aim of this study was to investigate whether symptomatic mononeuropathies are more frequent in diabetic patients without symptoms of acute or subacute polyneuropathy than in the general population.For this purpose, six hundred and forty two consecutive outpatients with various acute symptomatic mononeuropathies (radial, ulnar or peroneal neuropathy, Bell’s palsy or carpal tunnel syndrome) without symptoms of acute or subacute polyneuropathy were studied. The results showed that in 522 patients with symptomatic carpal tunnel syndrome (CTS) and in 38 patients with Bell’s palsy, the rate of diabetes was 7.7% and 10.5%, respectively. These rates do not differ significantly from the anticipated frequency of diabetes in the general population. On the other hand, in 18 patients with radial neuropathy at (or distally to) the spiral groove, in 41 patients with ulnar neuropathy and in 23 patients with peroneal neuropathy at the fibular head, the respective rates were 27.8%, 12.2 % and 30.4%. These rates are significantly higher than those anticipated according to the frequency of diabetes in the general population. The findings of the present study indicate that only focal limb neuropathies due to acute external compression are more frequent in diabetic patients.

APOE ε4 is associated with impaired verbal learning in patients with MS

Objective: To investigate the effect of APOE ε4 on different cognitive domains in a population of Greek patients with multiple sclerosis (MS). Methods: A total of 125 patients with MS and 43 controls were included in this study and underwent neuropsychological assessment with Rao’s Brief Repeatable Battery. All patients with MS were genotyped for APOE. The effect of APOE ε4 on different cognitive domains was investigated. Results: Fifty-one percent of patients with MS were cognitively impaired. E4 carriers had a sixfold increase in the relative risk of impairment in verbal learning vs noncarriers (OR 6.28, 95% CI 1.74 to 22.69). This effect was domain-specific and was not observed in other cognitive domains assessed by the battery. Conclusion: We found an association of APOE ε4 with impaired verbal learning in patients with multiple sclerosis.

Aetiopathogenesis and long-term outcome of isolated pontine infarcts

Background and purposeIsolated pontine strokes cause characteristic neurological syndromes and have a good short-term prognosis. The aim of this study was to examine the long-term survival, cumulative recurrence rate and clinical handicap of patients with isolated pontine infarcts of different aetiology.MethodsOne hundred consecutive patients with an isolated pontine infarction were identified by imaging studies and evaluated prospectively. After extensive study, cases were classified according to the aetiopathogenetic mechanisms: stroke due to basilar artery branch disease (BABD), small-artery disease (SAD) and large-artery-occlusive disease (LAOD). During a mean follow-up period of 46 months, stroke presentation and initial course, early and long-term mortality, disability and recurrence were evaluated.ResultsBABD was the most frequent cause of isolated pontine ischaemia (43 %), followed by SAD (34%) and LAOD (21%). Hypertension was the most prominent risk factor, especially among patients with SAD (94.1 %). Neurological impairment on admission was more severe in the LAOD group, followed by BABD. After 1 month patients with LAOD had the highest cumulative mortality (14.3%, p=0.026) and more severe disability (61.1%, p=0.001). Five-year mortality rate was 20.6%, 14% and 23.8% in the SAD-, BABD- and in LAOD-group respectively (p=0.776). Cumulative 5-year recurrence rate was 2.3 % for BABD, 14.3 % for LAOD, and 29.4 % for SAD (p=0.011).ConclusionsOverall long-term survival of patients with isolated pontine infarcts is good. Initial differences regarding short-term outcome in infarctions of different aetiology resolve with time. Effective secondary prevention among SAD patients may limit stroke recurrence and positively influence long-term prognosis.

Nucleo-cytoplasmic ratio in ageing skeletal muscle.

SummaryIn order to investigate possible changes in the nucleo-cytoplasmic ratio of the muscle fibres during ageing, samples of quadriceps femoris from 15 normal individuals whose age ranged from 17 to 82 years were studied (autopsy material). The mean lesser diameter and the number and size of the muscle fibre nuclei were calculated using a planimetric technique. It was found that nucleo-cytoplasmic ratio increased significantly after the age of 60 years. This was due to a decrease in the mean fibre size whilst the number and the size of myonuclei remained unchanged. The resemblance of this finding to denervation atrophy changes is noted.

Hereditary neuropathy with liability to pressure palsies emerging during vincristine treatment

Vincristine treatment is often the cause of peripheral neuropathy, usually reversible after the discontinuation of treatment or dose reduction.1 There are several reports of acute neurotoxicity caused by the vincristine treatment of patients with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease type 1A [CMT-1A]).2 Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited recurrent focal demyelinating neuropathy, characterized by painless nerve palsies at common sites of compression and entrapment of peripheral nerves. The most common cause of HNPP is a DNA deletion of a 1.5 Mb region on chromosome 17p11.2-p12, which includes the peripheral myelin protein (PMP) 22 gene (duplication of which causes CMT-1A).3 We report the case of a 37-year-old man with HNPP, revealed after vincristine treatment for non-Hodgkin lymphoma. A 37-year-old man developed a predominantly diffuse, large T-cell type non-Hodgkin lymphoma of intermediate grade, stage III. The patient received introduction chemotherapy with the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen, consisting of a total dose of cyclophosphamide 1,500 mg IV, doxorubicin 100 mg IV, and vincristine 2 mg IV, …

Hyperventilation-Enhanced Chorea as a Transient Ischaemic Phenomenon in a Patient with Moyamoya Disease

Introduction Moyamoya disease is a relatively rare and eventually underdiagnosed cerebral vasculopathy of unknown aetiology, which is characterised by progressive bilateral narrowing or occlusion of the terminal portion of the internal carotid artery and the proximal part of the anterior and middle cerebral artery, with the concomitant development of an abnormal meshwork of basal collateral vessels. The disease may also involve the posterior circulation, most commonly the posterior cerebral artery. The first symptoms usually become clinically evident and diagnosis is made during childhood or in young adult life. Epileptic seizures, migrainous headaches, transient ischaemic attacks or ischaemic strokes in children and haemorrhagic strokes in adults are the cardinal initial manifestations of this uncommon cerebrovascular disease [1–4]. Involuntary movements, such as dyskinesia, chorea or hemiballismus [1, 5], behavioural disturbances [6], neuropsychological deficits and mental deterioration [7] have rarely been described. Moyamoya disease has to be distinguished from the secondary moyamoya syndrome, which occurs mostly unilaterally and is associated with a series of other diseases [1, 8, 9]. The clinical differentiation is not easy since the symptoms of both entities are similar. Moyamoya disease has been predominantly described in Japan and other Asian countries [1, 2]. Smaller case series from the United States, Canada and Europe indicate a significantly lower incidence and prevalence of moyamoya disease outside Japan [10–12]. Another typical difference is that the distinction between childhood and adulthood cases that characterises the Japanese moyamoya disease is less clear in western populations. We describe a case of moyamoya disease with choreatic movements, which get dramatically enhanced by hyperventilation.