Transient acute hydrocephalus after aneurysmal subarachnoid hemorrhage and aneurysm embolization: a single-center experience.

PURPOSE: Acute hydrocephalus is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). It can be self-limiting or require cerebrospinal fluid diversion. We aimed to determine the transient acute hydrocephalus (TAH) rate in patients with aSAH treated endovascularly and evaluate its predictive factors. METHODS: A retrospective review of 357 patients with aSAH who underwent endovascular treatment from March 2013 to December 2019 was performed. Clinical and radiographic data were analyzed and risk factors with potential significance for acute hydrocephalus were identified. We constructed a new risk score, the Drainage Or Transiency of Acute Hydrocephalus after Aneurysmal SAH (DOTAHAS) score, that may differentiate patients who would experience TAH from those needing surgical interventions. RESULTS: Acute hydrocephalus occurred in 129 patients (36%), out of whom in 66 patients (51%) it was self-limiting while 63 patients (49%) required external ventricular drainage placement. As independent risk factors for acute hydrocephalus, we identified older age, poor initial clinical condition, aSAH from posterior circulation, and the extent of cisternal and intraventricular hemorrhage. The following three factors were shown to predict acute hydrocephalus transiency and therefore included in the DOTAHAS score, ranging from 0 to 7 points: Hunt and Hess grade ≥ 3 (1 point), modified Fisher grade 4 (2 points), and Ventricular Hijdra Sum Score (vHSS) ≥ 6 (4 points). Patients scoring ≥ 3 points had significantly higher risk for EVD (P < 0.0001) than other patients. CONCLUSION: The newly developed DOTAHAS score can be useful in identifying patients with transient acute hydrocephalus. Further score evaluation is needed.

Comparison between stenting and conservative management of posterior circulation perforator aneurysms: Systematic review and case series.

PURPOSE: Posterior circulation perforator aneurysms (PCPAs) are a rare type of intracranial aneurysms whose natural history and optimal clinical management are still largely unexplored. This study aims to report our experience with treating ruptured PCPAs and to provide a systematic review of the literature to compare the two most established treatment options, endovascular stenting, and conservative management including administration of antifibrinolytic drugs and watchful waiting. METHODS: We performed a systematic review of the literature following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Major databases were searched for case reports and case report series written in the English language between 1995 and 2020. Additionally, we retrospectively reviewed our stroke center database for cases of ruptured PCPAs between January 2014 and July 2020. Endovascular stenting and conservative treatment were compared using endpoints, including favorable outcome rate (mRS 0-2), occlusion rate, mortality rate, periinterventional complication rate, and re-hemorrhage rate. RESULTS: We identified 31 patients treated endovascularly using stents and 33 patients treated conservatively, with the administration of antifibrinolytic drugs in 3 of them. Our analysis showed no statistically significant difference between the groups, except for the occlusion rate. CONCLUSIONS: The optimal management strategy of PCPAs is still unknown, but stenting can be considered as an effective occlusion method with an acceptable complication rate. Preventive ventricular drainage may be necessary due to the high hydrocephalus rate encountered in ruptured PCPAs.

Spinal dural arteriovenous fistulas: a report on outcomes in a single-center retrospective cohort treated surgically and/or endovascularly.

AIM: To report on the outcomes of spinal dural arteriovenous fistulas (sDAVFs) treatment in a single-center retrospective cohort. METHODS: Data were retrieved on sDAVF cases treated surgically and endovascularly between January 2009 and January 2020. Sociodemographic, clinical, imaging data, and outcomes were analyzed. RESULTS: Thirty-four patients were identified: 11 female, mean age 64.1 ± 11.5 years; mean time of symptom duration 12 (range 1-149) months. The sDAVF locations were the following: 18 (62.1%) thoracic, 4 (13.8%) lumbar, 4 (13.8%) sacral, and 3 (10%) with multiple location feeders. All patients had a motor deficit and affected walking, and the majority had a sensory deficit, bowel, and bladder dysfunction. Fifteen (44.1%) patients underwent surgical treatment, 7 (20.6%) underwent endovascular treatment, and 12 (35.3%) underwent both (crossover). Radiological myelopathy showed regression in 19 (55.9%) patients. Overall, clinical improvement (decrease in modified Rankin score) following treatment was observed in 14 patients (41.2%), worsening in 1 (2.9%), while other had unchanged status. The proportion of patients with initial treatment failure markedly differed between the before-2014 and after-2014 period. Patients who failed to improve had more extensive myelopathy. CONCLUSION: Patients who underwent surgery or endovascular treatment had on average significant clinical recovery, while those who underwent treatment crossover had negligible improvement. The extent of myelopathy seems to be associated with clinical improvement.

Diffusion-weighted MRI: impact of the size of the ROI in detecting metastases in subcentimeter lymph nodes in head and neck squamous cell carcinoma.

PURPOSE: Our aim is to determine the impact of the size of ROI in detecting subcentimeter metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). Secondary aim is to determine the impact of the histopathologic grade of the primary cancer on the ADC value of the metastatic nodes. METHODS: The prospective study included 51 patients with histopathologically proven HNSCC at the primary site. Primary site includes oral cavity, oropharynx, larynx, and hypopharynx. ADC values of the lymph nodes were measured on ADC maps by placing two ROIs in the lymph nodes (0.2 cm2 in the center of the node and the whole node). Lymph nodes were dissected by levels, marked by the surgeon, and sent to the pathologist. RESULTS: By applying a smaller ROI, ADC values have greater sensitivity, specificity, NPV, PPV, and AUC in detecting metastasis compared to the ADC value of the entire node (88.0%, 80.73%, 90.7%, 75.9%, 0.912% versus 80.0%, 77.98%, 85% ,71.4%, and 0.819%, respectively) p < 0.001. Statistically significant negative correlation was established between the tumor grade and the ADC of lymph node at ROI 0.2 cm2and ROI of the whole lymph node (rho = - 0.425; p = 0.002, and rho = - 0.298; p = 0.038, respectively). CONCLUSION: ROI size affects the ADC value of the nodes. The higher histopathological grade of the primary tumor is inversely correlated with the ADC value of the lymph nodes.

Choline and N-acetyl aspartate levels in the dorsolateral prefrontal cortex at the beginning of the recovery phase as markers of increased risk for depressive episode recurrence under different duration of maintenance therapy and after it: a retrospective cohort study.

AIM: To evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression. METHODS: This retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model. RESULTS: NAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery. CONCLUSION: Patients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients.

Hypopituitarism after gamma knife radiosurgery for pituitary adenoma.

PURPOSE: The aim of the study was to investigate the incidence of and risk factors for hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenoma. MATERIALS AND METHODS: We conducted a retrospective analysis of the pituitary function of 90 patients who underwent GKRS for pituitary adenoma at the University Hospital Centre Zagreb between 2003 and 2014. Twenty seven of them met the inclusion criteria and the others were excluded from the study due to pituitary insufficiency which was present before GKRS. Eighteen patients had non-functioning and 9 patients had secretory adenomas. Median patients' age was 56 years (24-82). GKRS was performed using the Leksell gamma knife Model C. The median prescription radiation dose was 20 Gy (15-25) and the median tumor volume size was 3.4 cm3 (0.06-16.81). New onset hypopituitarism was defined as a new deficit of one of the three hormonal axes (corticotroph, thyreotroph, or gonadotroph) ≥3 months following GKRS. SPSS was used for statistical analysis, with the significance level at P<0.05. RESULTS: During the median follow-up period of 72 months (range 6-144), 30% of patients developed new hypopituitarism after GKRS. This corresponds to incidence of one new case of hypopituitarism per 15 patient-years. Age, gender, tumor function, tumor volume, suprasellar extension, prescription dose of radiation, as well as dose-volume to the pituitary gland, stalk and hypothalamus were not predictive factors for the development of hypopituitarism. CONCLUSIONS: In our cohort of patients with pituitary tumors who underwent GKRS, 30% developed new hypopituitarism during the follow-up period.

Long-term angiographic outcome of stent-assisted coiling compared to non-assisted coiling of intracranial saccular aneurysms.

AIM: To compare angiographic result at long-term follow-up, and rates of progressive occlusion, recurrence, and retreatment of stent-assisted coiled (SAC) and non-assisted coiled (NAC) intracranial saccular aneurysms. METHODS: Retrospective evaluation of department records identified 260 patients with 283 saccular intracranial aneurysms who had long-term angiographic follow-up (more than 12 months) and were successfully treated with SAC (89 aneurysms) or NAC (194 aneurysms) at the University Hospital Center Zagreb from June 2005 to July 2012. Initial and control angiographic results in both groups were graded using Roy/Raymond scale, converted to descriptive terms, and the differences between them were evaluated for statistical significance. A multivariate analysis was performed to identify factors related to progression of aneurysm occlusion and recurrence at follow-up, and those related to aneurysm retreatment. RESULTS: There were more progressively occluded aneurysms in SAC group (38 of 89 aneurysms, 42.7%) than in NAC group (46 of 194, 23.7%) (P=0.002), but there were no significant differences in the rates of recanalization, regrowth, and stable result. Multivariate logistic regression identified the use of stent as the most important factor associated with progressive occlusion (P=0.015, odds ratio 2.22, 95% confidence interval 1.17-4.21), and large aneurysm size and posterior circulation location as most predictive of aneurysm recurrence and retreatment. CONCLUSION: The use of stent is associated with delayed occlusion of initially incompletely coiled aneurysms during follow-up, but does not reduce the rate of recurrence and retreatment compared to coiling alone. Long-term angiographic follow-up is needed for both SAC and NAC aneurysms.

Parkinsonian syndrome and ataxia as a presenting finding of acquired hepatocerebral degeneration.

The term "acquired hepatocerebral degeneration" (AHD) was coined to describe clinical entity distinct from genetically defined Wilson's disease. AHD is chronic neurological disorder, characterized by extrapyramidal and neuropsychiatric symptoms accompanied with advanced liver disease with portosystemic shunts. In majority of AHD cases, extrapyramidal symptoms appear in the presence of known liver disease. Here we present a patient with subacute onset of bilateral, asymmetric, hypokinetic-rigid syndrome and ataxia as initial presentation of liver cirrhosis. Manganese toxicity have major role in AHD pathogenesis. Failure of liver detoxification and presence of portosystemic shunting enables neurotoxic substance of manganese to avoid hepatic metabolism and to enter and accumulate in central nervous system. Predilection brain regions for manganese deposits are globus pallidum (GP) and substantia nigra (SN). Characteristic MRI findings of bilateral, symmetrical hyperintensities of GP and SN on T1-weighted sequences supported the diagnosis of AHD in our patient. In addition, increased T2 signal in dendate nuclei seen in our patient is rare radiological finding. So far, no consensus guidelines regarding medical treatment of AHD exist. We initiated low-dose levodopa treatment, but failed to provide beneficial effect. In conclusion, AHD is distinct clinical entity that should be included in differential diagnosis of both typical and atypical parkinsonian syndromes. Furthermore, our case highlights the importance of performing MRI in patients with atypical parkinsonism.

Fatal outcome of posterior "reversible" encephalopathy syndrome in metastatic colorectal carcinoma after irinotecan and fluoropyrimidine chemotherapy regimen.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity characterized by headaches, altered mental status, seizures, and visual disturbances. It can occur in many different clinical entities such as severe hypertension and pre-eclampsia, or due to cytotoxic or immunosuppressive therapies. The pathogenesis of PRES is unclear, with dysregulated cerebral auto-regulation and endothelial dysfunction as important mechanisms proposed. Endothelial dysfunction is important especially in cases associated with cytotoxic therapies. Herein, we describe a patient with PRES with fatal outcome, who presented 5 days after the infusion of cycle 1 of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy, without prior hypertension and other comorbidity, suggesting a link between PRES and FOLFIRI regimen. To our knowledge, this case report is the first describing PRES after FOLFIRI regimen, although others have described PRES after FOLFIRI with bevacizumab in colonic cancer patients.

A 5-Year Follow-Up after Endovascular Treatment of 402 Intracranial Aneurysms-A Single-Centre Experience.

The aim of our study was to evaluate the early and long-term clinical and morphological outcomes of the endovascular treatment of ruptured and non-ruptured intracranial aneurysms in a cohort of patients from a single centre. We retrospectively analysed the treatment outcomes of 402 endovascularly treated intracranial aneurysms with an average follow-up of 5.5 years. All included patients were treated with endovascular techniques (coil, stent or both). We analysed patient demographics, risk factors for an aneurysm rupture, aneurysm characteristics, and clinical and angiographic complications and outcomes. We analysed and compared the data from the two groups, ruptured aneurysms (RAs) and unruptured aneurysms (UAs), separately. Out of the 318 patients included, a good early clinical outcome was achieved in 78.5% of RAs and in 95.3% of UAs. No complications occurred in 87.71% of patients with UAs and in 80.45% with RAs. The periprocedural rupture rate for UAs and RAs was 0.8% and 2.2%, respectively. The rate of thromboembolic events was 4.8 and 8% for UAs and RAs, respectively. A retreatment due to the recanalisation was required in 9.21% of patients with UAs and in 16.66% of patients with RAs. The results from our centre showed an overall favourable clinical outcome with acceptable periprocedural complications for both RAs and UR aneurysms and proved the endovascular method as safe and effective in the treatment of intracranial aneurysms.

Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping.

PURPOSE: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). METHODS: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. RESULTS: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. CONCLUSION: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes.

Comparative Targeted Metabolomics of Ischemic Stroke: Thrombi and Serum Profiling for the Identification of Stroke-Related Metabolites.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke. Metabolomics has been shown as a promising tool for biomarker discovery since many post-ischemic metabolites can be found in the plasma or serum of the patient. In this research, we performed a comparative targeted metabolomic analysis of stroke thrombi, stroke patient serums, and healthy control serums in order to determine the alteration in the patients' metabolomes, which might serve as biomarkers for early prediction or stroke prevention. The most statistically altered metabolites characterized in the patient serums compared with the control serums were glutamate and serotonin, followed by phospholipids and triacylglycerols. In stroke thrombi compared with the patients' serums, the most significantly altered metabolites were classified as lipids, with choline-containing phospholipids and sphingomyelins having the highest discriminatory score. The results of this preliminary study could help in understanding the roles of different metabolic changes that occur during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers for ischemic stroke.

Isolated and persistent cognitive dysfunction in a patient with acute disseminated encephalomyelitis.

We report a case of pathology-proven acute disseminated encephalomyelitis (ADEM) in which the patient's symptoms were solely cognitive. Although cognitive dysfunction is a well-recognized symptom in adults with multiple sclerosis, cognitive assessment of adults with ADEM has rarely been reported. A 35-year-old woman was referred to our center for evaluation of cognitive disturbance and demyelinating lesions seen on brain magnetic resonance imaging (MRI). We performed a neurologic examination, full neuropsychological assessment, brain MRI, blood and cerebrospinal fluid analyses, visual evoked potentials, and brain biopsy. The patient's Mini-Mental State Examination score was 26/30. Cognitive assessment revealed multiple severe dysfunctions, mainly in executive and attention tasks. She scored below the normal range on the Digit Span Forward and Backward Test and the Trail Making Test Part B. The Frontal Assessment Battery showed deficits in mental flexibility, motor programming, and inhibitory control. She also scored in the impaired range on tests of verbal fluency and memory. The brain MRI and biopsy confirmed a diagnosis of ADEM. This case report points to the limitations of relying on clinical presentation, neuroimaging, and current controversial diagnostic criteria in diagnosing ADEM in adults, and highlights the essential role of pathologic evaluation.

Young stroke patient with patent foramen ovale and intracranial stenosis-a case report.

The prevalence of patent foramen ovale is approximately 20% in the global population. In patients under the age of 55 years, it has been proven as a cause of acute ischemic embolic stroke of otherwise undetermined source. We present a case of a 25-year-old patient who experienced an acute stroke of dominant hemisphere due to internal carotid artery occlusion.The patient underwent mechanical thrombectomy, followed by acute intracranial stenting due to persistent subocclusion of internal carotid artery. Further diagnostic investigations revealed a significant patent foramen ovale. During subsequent follow-up periods, the patient encountered multiple transient ischemic attacks despite receiving antithrombotic therapy. The indicated angiography examination revealed in-stent stenosis and thrombosis, which were resolved after optimal medical treatment. Following patent foramen ovale closure, the patient remained free from further neurological events during the subsequent two-year follow-up periods. This case emphasizes the necessity of comprehensive diagnostic evaluations in young individuals with stroke and underscores the importance of prudent slection of medical therapies.

Endovascular treatment of AVM-associated aneurysm of anterior inferior cerebellar artery through persistent primitive hypoglossal artery.

We present a patient with the combination of persistent primitive hypoglossal artery and the origin of left common carotid artery from the brachiocephalic trunk, who had subarachnoid haemorrhage caused by a ruptured aneurysm. The aneurysm was on distal anterior inferior cerebellar artery which was a feeder to cerebellar arterio-venous malformation.

Clinical sensitivity and specificity of multiple T2-hyperintensities on brain magnetic resonance imaging in diagnosis of neurofibromatosis type 1 in children: diagnostic accuracy study.

AIM: To determine the prevalence, number, and location of multiple (≥2) T2-hyperintensities on brain magnetic resonance imaging (MRI) in children with neurofibromatosis type 1 (NF1) and their correlation with age, and to establish their sensitivity, specificity, and accuracy for the diagnosis of NF1 in children, especially in the early age (2-7 years). METHODS: We performed a cross-sectional study of 162 patients with NF1 from Croatian Neurofibromatosis Association Database and 163 control children between the ages of 2 and 18 years who underwent brain MRI between 1989 and 2009. RESULTS: Multiple T2-hyperintensities were present in 74% of NF1 patients and 1.8% of controls. They were mainly located in the basal ganglia, brainstem, and cerebellum and were significantly decreased in prevalence and number in the older age. T2-hyperintensities had excellent diagnostic accuracy with the area under the receiver operating characteristic (ROC) curve of 0.849 and 95% confidence interval (CI) of 0.805-0.886. The diagnostic sensitivity, specificity, and accuracy rate of T2-hyperintensities for NF1 were highest in the youngest age (2-7 years): 81% (95% CI 71%-89.1%), 99% (95% CI 92.3%-100%), and 85.8 (95% CI 83.3-93.8), respectively. CONCLUSION: This study strongly suggests the inclusion of T2-hyperintensities on brain MRI on the list of diagnostic criteria for NF1, especially in children of early age, when the clinical penetration of the NF1 gene has not yet been completely finished.

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.

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.