Arylsulfatase a gene polymorphisms in relapsing remitting multiple sclerosis: genotype-phenotype correlation and estimation of disease progression.

Arylsulfatase A (ASA) is a lysosomal enzyme involved in catabolism of cerebroside-sulfate, major lipid constituent of oligodendrocyte membranes. Various polymorphisms in ASA gene have been described, leading to different levels of enzyme deficiency. Progressive demyelination occurs in metachromatic leukodystrophy (MLD), while the condition of ASA-pseudodeficiency (ASA-PD) is suggested to contribute to complex pathogenesis of multiple sclerosis (MS). This work presents usefulness of genotype-phenotype correlation in estimation of disease severity and progression. The presence of two most common mutations associated with ASA-PD was analyzed in 56 patients with diagnosis of relapsing-remitting multiple sclerosis, by polymerase chain reaction restriction fragment length polymorphism method. In MS patients confirmed as ASA-PD mutations carriers, arylsulfatase activity was determined in leukocyte homogenates by spectrophotometry. To determine whether there is a difference between disability level and/or disease progression in patients with or without mutations we have estimated disability level using Expanded disability status scale (EDSS) and disease progression using Multiple sclerosis severity score (MSSS). Correlation of genotypes and disease progression was statistically analyzed by Kruskal-Wallis test. Patients showing higher MSSS score and found to be carriers of both analyzed ASA-PD mutations were additionally examined using conventional magnetic resonance (MR) techniques. The presence of either one or both mutations was determined in 13 patients. Lower ASA activities were observed in all MS patients carrying the mutations. Nine of the mutations carriers had mild disability (EDSS=0-4.0), 1 had moderate disability (EDSS=4.5-5.5), and 3 had severe disability (EDSS > or = 6.0). On the other hand, only 3 MS patients who were mutation carriers showed MSSS values lower than 5.000 while in other MS patients-mutation carriers the MSSS values ranged from 5.267 to 9.453. Comparison of MR findings between MS patients, mutations carrier vs. non-carrier, matched for sex, age and disease duration, showed that the total number of lesions and the number of hypointense lesions on T1-weighted images was greater in MS patient carrying the ASA-PD mutations. Our results on genotype-phenotype correlation analysis indicate a possible contribution of detected arylsulfatase A gene polymorphisms to the clinical severity of multiple sclerosis, estimated by EDSS, MSSS and MR findings. The MSSS proved to be more appropriate indicator of disease progression and should be more frequently used in clinical practice especially for comparison of disease progression in different groups of patients and identification of factors that may influence disease progression such as the presence of gene polymorphisms.

Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report.

Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.

The gynaecological-obstetrical practice of the renaissance physician Amatus Lusitanus (Dubrovnik, 1555-1557).

OBJECTIVE: A gynaecological-obstetrical causation review in Dubrovnik from 1555 to 1557. Extract from the book "Curationum Medicinalium Centuriae V et VI" Amatus Lusitanus. METHOD: A thorough life and work archive study of Amatus Lusitanus has been made and, for this review, extracted his gynaecological-obstetrical causation observations and annotations. RESULTS: Amatus Lusitanus was an undisputed, reputable and respected medical figure during the mid 16th century. He decisively focused on intern medicine, incorporating the gynaecological-obstetrical field. His work and skill, most assuredly, contributed to the better comprehension, acknowledgement and reputation of the gynaecological-obstetrical practice, thus leaving repute and respect in medical history latitude. CONCLUSION: All these cases occurred in Dubrovnik during 1555-1557 and Amatus is assuredly an excellent observer and exactist, extracting the "relevant from the non-relevant" even in Dubrovnik's gynaecological-obstetrical daily happenings. He thoughtfully concludes his inability to remedy a malignant, advanced illness of the uterus, presumes an utero-vesico-intestinal fistula and openly speaks of medical ineptness of this causation. Proud of his invention in treating "contracted nipples"; correct in his advice and recommendations of "long and difficult births". Impartial in his perception of puerperal sepsis and its unfavourable pathology outcome. His description of "hormone insufficiency" is concise and precise; the preferred procedure in an "abortus in tractu" is purposeful and meaningful. He closely works with other physicians living and working in Dubrovnik; conscientiously directing surgeons in procedures of stillborn child births. He explains and treats pyschosexual disturbances "without fault" and in concurrence with, not only, the contemporary knowledge of such sexual disturbances, but also in concurrence with contemporary psychiatric procedures that, even today, are applied in such pathology treatment.