Nikolaos Kalfakis

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.

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.

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

ObjectiveTo 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. MethodsPatients 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. ResultsFrom 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. ConclusionsWe 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.

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.

CSF biomarker profile and diagnostic value in vascular dementia

Background and purpose:  The differential diagnosis between vascular dementia (VD) and Alzheimer’s disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (τT) or hyperphosphorylated at threonin‐181(τP‐181) form and beta amyloid peptide 1–42 (Aβ42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD.

Huntington's disease in Greece: the experience of 14 years.

Panas M, Karadima G, Vassos E, Kalfakis N, Kladi A, Christodoulou K, Vassilopoulos D. Huntingtons disease in Greece: the experience of 14 years.

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, …

Migraine with aura : Segregation analysis and heritability estimation

A genetic study was performed in a group of 60 migraine patients and their first‐degree relatives as well as in a group of sex‐ and age‐matched controls. Segregation analysis showed that multifactorial inheritance seems to be the most probable mode of genetic transmission. Heritabilities were estimated according to the sex of probands and relatives.

Severe dopaminergic pathways damage in a case of chronic toluene abuse

INTRODUCTION Toluene toxicity primarily affects central nervous system white matter, causing a characteristic brain MRI pattern. CASE REPORT A toluene addicted man, after an abstinence period and a treatment with neuroleptics, presented with severe worsening of preexisting generalized tremor, opsoclonus, dysarthria, gait inability, jerky tendon reflexes and behaviour disorders. Magnetic resonance imaging showed mild leukoencephalopathy and hypointensities in deep gray matter nuclei. The DaT-scan revealed a decrease in presynaptic dopamine reuptake. CONCLUSION Clinical and neuroradiological findings and the possible sensitivity to neuroleptics indicate dopaminergic impairment. Our case suggests that chronic toluene abuse causes presynaptic dopaminergic depletion.