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

A large scale genetic and epidemiological study of Huntington's disease (HD) was carried out in Greece from January 1995 to December 2008. Diagnostic testing was carried out in 461 symptomatic individuals, while 256 were tested for presymptomatic purposes. The diagnosis of HD with a CAG expansion ≥ 36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 2.5 to 5.4:100,000, while the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) sent for confirmation. The false-positive cases 15.6% were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was 8.6%. A prenatal test was requested in six pregnancies. The findings of our study do not differ significantly from those of similar studies from other European countries despite the relative genetic isolation of Greece. Of interest is the identification of clusters of HD in Greece. The presence or absence of a family history of HD should be interpreted cautiously, during the diagnostic process.

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 (tau(T)) or hyperphosphorylated at threonin-181(tau(P-181)) form and beta amyloid peptide 1-42 (A beta 42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD. METHODS: The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls. RESULTS: Alzheimer's disease and MD showed increased levels of tau(T), tau(P) and reduced levels of A beta 42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying >or=85% of patients, either in the form of a discriminant function or in the form of the tau(T) x tau(P-181)/A beta 42 formula. CONCLUSIONS: Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.

A case of refractory secondary paroxysmal kinesigenic dyskinesia with high sensitivity to phenytoin monotherapy.

We report on a 42-year-old man with paroxysmal kinesigenic dyskinesia who was referred as a refractory case to any drug used in the past as monotherapy or in combination. Our decision to discontinue his current combined medication and to administer only high-dose phenytoin led to significant improvement. It is of interest to note that the previous use of phenytoin in combination with other antiepileptic and neuroleptic drugs had no effect. In addition, the co-administration of gabapentin led to a dramatic recurrence of the episodes.

Pseudodominant Friedreich's ataxia with phenotypic heterogeneity.

OBJECTIVE: A family with a clinically heterogeneous progressive ataxia in two generations is presented. METHODS: Having eliminated mutations within the known dominant spinocerebellar ataxia genes, the family was investigated for expansion at the Friedreich's gene. RESULTS: The affected members (father, son and daughter) were homozygous for the mutation at the Friedreich's gene, while the unaffected (the mother and her sister) were heterozygous. CONCLUSION: This pseudodominant form of Friedreich's ataxia should be considered in families with an apparently autosomal dominant progressive ataxia in conjunction with sensory neuropathy and pyramidal signs.

Psychosis or simply a new manifestation of neurosyphilis?

The widespread use of antibiotics in recent years has caused a significant reduction in the incidence of neurosyphilis and changes in its clinical features. We present a case that initially presented as persistent headache and untreatable psychosis. Neurosyphilis was diagnosed during the clinical evaluation. Blood serum analyses for syphilis were positive for rapid plasma reagin titres, the Venereal Disease Research Laboratories test and fluorescent treponemal antibody absorption. A lumbar puncture was performed and cerebrospinal fluid analysis resulted in the diagnosis of neurosyphilis. The patient completed a 2-week course of treatment with aqueous crystalline penicillin G and his symptoms subsequently improved. We suggest that neurosyphilis should always be included in the differential diagnosis of untreatable psychosis.

Platelet monoamine oxidase activity in subjects tested for Huntington's disease gene mutation.

Monoamine oxidase activity (MAO) has been related to neuronal damage, since the oxidative deamination of biogenic amines produces free radicals that may enhance oxidative stress. Elevated enzyme activities in brain (MAO-A and MAO-B forms) and in platelets (MAO-B form) have been reported in several degenerative diseases, indicating that MAO activity may be involved in the disease progression. We estimated platelet MAO activity in a group of 59 patients (34 males) with HD, 20 subjects (7 males) at risk, and 29 (14 males) healthy subjects with positive family history for HD, categorized according to clinical features and the number of CAG repeat units (CAG-RN) at the Huntington gene. A group of 64 subjects (36 males) with negative family history for HD served as controls. In contrast to some previous studies, platelet MAO activities in both male and female patients (CAG-RN 40 to 62) with overt symptomatology, were not different compared to same sex control subjects. Subjects at risk (CAG-RN 39 to 52), though, showed significantly lower activities compared to same sex patients or controls. MAO activities seem to increase with disease progression, and tend to be higher in patients with dementia. The increases may be an epiphenomenon of disease pathology, but the possibility that an increase in the expression of the enzyme precedes the onset of the disease and contributes to enhanced oxidative stress should be considered in future longitudinal studies as a possible mechanism that accelerates disease progression.

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.

Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis.

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n = 72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.

Beck Depression Inventory in the detection of depression among neurological inpatients.

The validity of the Beck Depression Inventory (BDI) was assessed in a group of 150 neurological inpatients using Receiver Operating Characteristic analysis and DSM-III-R as external criterion. As regards depressive disorders as a whole, it was found that the best trade-off between sensitivity and specificity was the cutoff score of 20. The discriminating ability of the BDI for major depressive disorder was quite satisfactory at the cutoff score of 29 contrary to the dysthymic disorder in which the discriminating power of the BDI was not acceptable. In conclusion, the use of the BDI in neurological settings is useful with cutoff scores depending on the research purposes.

An epidemiological study of headaches among medical students in Athens.

In order to study the prevalence of frequent headaches among the medical students of Athens University, an epidemiological survey was carried out among 588 medical students (318 men and 270 women), with mean age 23.5 years. Two questionnaires were designed for the study: one general, consisting of 10 questions and a second one, specific for headache sufferers, consisting of 117 questions. All those with headache who voluntarily completed the two questionnaires also underwent a neurological examination. Thirty point eight percent of men and 50.3% of women reported various headache attacks during the previous 6 months (39.6% in both sexes). However, only the 11.9% of students (from both sexes) reported that they suffered from disturbing headaches. The 6-month prevalence of migraine was 2.4% and 9.5% for tension-type headache (in both sexes). Cluster headache was not traced. The prevalence of nonclassifiable headaches (according to the criteria of the International Headache Society) was 0.85%. Headache was correlated to sex (more frequent among women) and anxiety level (Hamilton scale for anxiety). Headache prevalence was not correlated to smoking and social class.

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. Our findings favor multifactorial inheritance, but the contribution of a major gene can not be excluded.

Type II glycogenosis and thyroxine binding globulin deficiency in the same family.

An eight-member family is presented with two female members suffering from the juvenile form of acid maltase deficiency (AMD), the diagnosis confirmed by biochemical study of muscle. Biochemical leucocyte investigation revealed reduced a-glucosidase activity in both patients, a brother and the parents. Endocrinological study of the family disclosed reduced levels of thyroxine binding globulin (TBG) in the father and the three daughters. We consider the co-existence of AMD and TBG deficiency interesting, as thyroxine seems to play a role in the activation of acid maltase.

Size and proportion of fiber types in human muscle fascicles.

Size and distribution of 2 histochemical types of muscle fibers within the human muscle fascicle were investigated. Cryostat sections (ATPase, pH 9.4) were studied from 15 quadriceps femoris, 15 biceps brachii and 15 deltoid muscles taken at autopsy from 12 males and 9 females who had no history of neuromuscular disease. The number and the lesser diameter of type 1 and type 2 fibers were counted and percentage and mean diameter of the 2 types of fibers were calculated separately for periphery and interior of randomly selected fascicles. The results showed that a progressive age-related reduction of the diameter of type 2 fibers is observed and the predominance of type 2 fibers in the periphery is a constant finding in all muscles studied, regardless of sex and age.

GHQ-28 as an aid to detect mental disorders in neurological inpatients.

The prevalence of mental disorders (DSM-IIIR criteria) among 107 neurological inpatients was estimated, as well as the extent to which disorders were detected by neurologists. The validity of the scaled version of the General Health Questionnaire (GHQ-28) was evaluated using Receiver Operating Characteristic (ROC) analysis and DSM-IIIR as external criteria. Of the 107 patients who submitted to a structured psychiatric interview (SCID-R), 56 (52.3%) showed evidence of a mental disorder. Major depressive episode (n = 16), generalized anxiety disorders (n = 13) and dysthymia (n = 12) were the most frequent diagnoses. The neurologists recognized only 13/107 cases (12.1%). Significantly more women than men exhibited some form of mental disorder. The validation of GHQ-28 in the series of 107 neurological inpatients indicated that the best trade-off between sensitivity and specificity was the cut-off score of 5/6. The high occurrence of mental disorder, in association with the low rate of detection by the neurologists, points to the need for special attention to be paid to this problem by staff and experts.

External ophthalmoplegia with ragged-red fibres and acetylcholine receptor antibodies.

The cases of two elderly women with external ophthalmoplegia, generalized muscle weakness and serum anti-acetylcholine receptor antibodies, are presented. The electophysiological studies showed a myopathic pattern but no indications of myasthenia after repetitive stimulation. The edrophonium test was negative and there was no response to anticholinesterase medication. In addition, elevated serum lactic acid levels and ragged-red muscle fibres in the muscle biopsy, were observed in both patients. These findings are discussed in relation to the fact that anti-acetylcholine receptor antibodies are diagnostic of myasthenia gravis, whereas ragged-red fibres and elevated lactic acid are correlated with mitochondrial myopathies.