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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.

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.

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Rationale: Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates., Objectives: To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy., Methods: Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling., Results: Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77)., Conclusion: Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

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.

Gaucher disease type 3 (GD3) is a severely debilitating disorder characterized by multisystemic manifestations and neurodegeneration. Enzyme replacement therapy alleviates visceral signs and symptoms but has no effect on neurological features. Ambroxol has been suggested as an enzyme enhancement agent. Some studies have confirmed its effectiveness in preventing the progression of neurological manifestations of neuronopathic Gaucher disease. In this study, we report two GD3 siblings in whom ambroxol combined with enzyme replacement therapy was initiated at different stages of the disease. We demonstrate the enzyme enhancement effect of ambroxol on L444P/H225Q;D409H glucocerebrosidase activity through results of fibroblast studies and long-term clinical outcomes of the two patients. The sibling diagnosed at the age of four-and-a-half years with significant neurological involvement manifested relatively rapid improvement on ambroxol treatment, followed by stabilization of further course. The younger sibling, in whom the treatment was started at seven weeks, displayed attention deficit and low average cognitive functioning at the age of seven years, but did not manifest other neurological symptoms. The difference in neurological outcomes indicates that ambroxol delayed or even halted the evolution of neurological manifestations in the younger sibling. This observation suggests that early initiation of ambroxol treatment may arrest neurological involvement in some GD3 patients., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

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 cm 2 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 cm 2 and 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.

Hepatitis-associated aplastic anemia is a rare syndrome in which bone marrow failure occurs within weeks to 1 year after attack of acute hepatitis. Studies suggest that cytotoxic T lymphocytes play a central role in bone marrow destruction, but the exact etiology remains unknown. Bone marrow transplantation or immunosuppressive therapy are primary curative options. We present a case of a young male who was admitted to the Department of Gastroenterology and Hepatology for acute hepatitis of an unknown cause. Liver biopsy revealed extensive inflammatory process with hepatocyte necrosis. Forty days later, new onset pancytopenia was identified. Bone marrow biopsy showed severe hypocellularity, and he was diagnosed with severe hepatitis-associated aplastic anemia. Treatment with cyclosporine was initiated, but with inadequate response, and pretransplant evaluation was started. Due to severe neutropenia, following alveotomy procedure, the patient developed deep neck infection with consequent airway obstruction. Despite urgent treatment, his condition deteriorated to sepsis with lethal outcome., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Background: Cognitive deficits after perinatal brain lesion in preterm infants are among the most common neurodevelopmental disturbances. The relationship between structural changes on at term magnetic resonance imaging (MRI) and cognitive deficits in the preschool age should be a special focus due to timely intervention. The aim of this study was to correlate qualitative and quantitative MRI parameters of perinatal brain lesion in preterm children, on early neonatal MRI and follow up MRI, with general and specific cognitive functions in the preschool age., Methods: Twenty-one preterm infants with verified perinatal lesions based on clinical and ultrasound data underwent a brain MRI at term-equivalent age and a second MRI between 3 and 5 years of age. Qualitative and quantitative MRI analyses were done. All subjects underwent cognitive assessment (3-5 years) using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Developmental Neuropsychological Assessment (NEPSY-II)., Results: Results show that many structural changes on at term MRI and on follow up MRI in preterm born children moderately correlate with specific cognitive deficits in preschool age. At term equivalent MRI, white matter changes and cortical thickness correlate to general and specific cognitive functions in infants born preterm. By analyzing follow up MRI at preschool age, structural changes of different white matter segments, corpus callosum, cortical thickness and lobe volume correlate to some specific cognitive functions., Conclusion: Besides general cognitive delay, specific cognitive deficits in preterm children should be targeted in research and intervention, optimally combined with MRI scanning, providing timely and early intervention of cognitive deficits after perinatal brain lesion. Our results, as well as previously published results, suggest the importance of detailed preschool neuropsychological assessment, prior to enrolment in the school system. Although preliminary, our results expand our understanding of the relationship between early brain developmental lesions and cognitive outcome following premature birth., (Copyright © 2019. Published by Elsevier B.V.)

Background: Acute stent thrombosis is a rare adverse event following endovascular treatment of carotid artery. Experience on the topic is scarce, making the therapeutic approach a clinical challenge. In cases of intraprocedural acute carotid stent thrombosis, thromboaspiration, thrombectomy, and thrombolysis have been used as successful modalities for achieving recanalization., Case Description: We describe a case of carotid artery dissection treated endovascularly and complicated by intraprocedural stent thrombosis, which was ultimately managed by emergent extracranial-intracranial bypass with radial artery graft connecting the external carotid artery to the ipsilateral middle cerebral artery., Conclusions: Neurosurgical management may represent a rescue option for otherwise unmanageable acute carotid stent thrombosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This report describes a case of neurosyphilis presenting with memory disturbances, attention deficit, and acute psychotic decompensation in an immunocompetent man. Despite the known connection of neurosyphilis with psychiatric symptoms, this cause often remains unrecognized. This report emphasizes the importance of maintaining a suspicion for the disease in patients with vague symptoms and describes the diagnostic difficulties., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Background: The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy., Methods: 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later., Results: Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio., Conclusion: Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.

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 cm 3 (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.

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.

Objectives: To evaluate the role of clinical parameters, MRI and ocular VEMP (oVEMP) and cervical VEMP (cVEMP) as predictors of development of chronic vestibular insufficiency after vestibular neuritis., Methods: Twenty-six patients with vestibular neuritis were included: 15 patients (58%) showed complete clinical recovery, and 11 patients (41%) were diagnosed with the syndrome of chronic vestibular insufficiency. Clinical parameters (vomiting, nystagmus, postural stability, and nausea) were assessed at diagnosis. MRI was performed within 3 months and VEMP within 6 days and at 1 year after the initial presentation. The amplitude asymmetry ratio (AR) was calculated using the following formula: AR=((healthy side-affected side)/(healthy side+affected side) × 100)., Results: Of all studied parameters, only chronic white matter supratentorial lesions present on brain MRI negatively correlated with clinical recovery (Phi coefficient=-0.637, p=0.001). The logistic regression analysis showed that positive brain MRI and older age reduced odds for clinical recovery. There was no correlation between clinical recovery and oVEMP AR recovery between groups (p=0.781). Seven patients showed improvement, and 19 showed worsening on oVEMP AR after a 1-year follow-up. Statistical regression model for predicting the outcome of clinical recovery using asymmetry score recovery, as an independent variable, was not statistically significant., Conclusions: Older age and chronic white matter lesions on brain MRI are positive predictors of development of chronic vestibular insufficiency after vestibular neuritis. VEMPs are not useful in predicting the development of chronic vestibular insufficiency., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

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.

The impact of glutathione S-transferases (GSTs) detoxification pathway on complex pathogenesis and heterogeneity of clinical findings in multiple sclerosis (MS), particularly the exact correlation between indicators of clinical severity and different GST genotypes, has not yet been fully elucidated. The aim of the study was to assess the relationship between disability level in multiple sclerosis (estimated by Kurtzke Expanded Disability Status Scale), disease progression (estimated by Multiple Sclerosis Severity Score), the level of brain atrophy and lesion load (determined by MRI) and detoxification status (analyzing glutathione S-transferase P1, GSTP1, genotype profile), in a group of 58 MS patients and 68 age/gendermatched controls. The results present the first evidence on significantly higher frequency of GSTP1 C341T polymorphism (C-T transition) in healthy subjects compared to MS patients, suggesting it may act as a moderating factor in developing MS clinical phenotype. Gender-dependent distribution of the C341T polymorphism was found in both MS patients and controls, with higher frequency of C-T transition in females. In addition, preliminary data showed higher proportion of male MS patients with higher median MSSS scores, as well as lower brain atrophy level and lesion load in MS patients carrying the C341T mutation. Observed gender difference in distribution of the C341T polymorphism in MS patients, as well as in disease progression, suggests that GSTP1 detoxification pathway occurs in a gender-dependent manner and could therefore add to clinical severity in male MS patients.

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.

We herein report the case of a 32-year-old woman with sudden onset ataxia, limb dysmetria and somnolence. Emergency radiological findings showed bilateral cerebellar and thalamic infarctions as a result of a basilar artery occlusion. The patient was treated with intra-arterial (IA) and mechanical thrombolysis 12 hours after symptom onset and showed an excellent recovery. A diagnostic workup revealed a tumor mass on the mitral valve that was surgically removed, while a histological analysis confirmed a diagnosis of cardiac papillary fibroelastoma.

Autosomal recessive ataxias caused by mutations of the polymerase γ (POLG) gene make an important group of progressive ataxias accompanied by a diverse spectrum of neurological disorders. Because the clinical picture can be quite miscellaneous, it is challenging to assort patients to any of the currently described syndromes; therefore, to provide such a patient with a conclusive diagnosis can be challenging for the neurologist. A typical magnetic resonance imaging finding is probably the most useful landmark in the diagnostic process, which will steer the clinician toward POLG gene testing. To illustrate this, we present a case of progressive ataxia caused by A467T and W748S mutations of POLG gene, who presented with overlapping symptoms of autosomal recessive mitochondrial ataxic syndrome and SANDO, as well as choreoathetotic movements and dysphonia. After lengthy investigations, magnetic resonance imaging showed T2 and FLAIR hyperintensities in the thalamus, inferior olives, and cerebellum, which led us to the analysis of POLG mutations.

Primary position upbeat nystagmus is a rare clinical finding. We report a patient with clinically isolated syndrome suggestive of multiple sclerosis who presented with primary position upbeat nystagmus. MRI revealed a demyelinating lesion in the lower medulla, which affected the nucleus intercalatus; this type of lesion inhibits the flocculovestibular inhibitory pathway, thereby causing upbeat nystagmus. Nystagmus still persisted after pulsed corticosteroid therapy. This could be due to a loss of central adaptation of the vestibulo-ocular system in our patient, because of more diffuse brainstem damage, shown on vestibular-evoked myogenic potentials as delayed latencies on both sternocleidomastoid muscles and a conduction block for the left extraocular muscles., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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.

Cerebral sinovenous thrombosis in neonatal period may cause neurological impairment, epilepsy, and lead to stroke. It is caused primarily by coagulopathy of numerous reasons, occasionally perinatal asphyxia, traumatic delivery and hyperhomocysteinemia. Dandy-Walker malformation is characterized by agenesis or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa. Dandy-Walker malformation, variant, and mega cisterna magna represent a spectrum of developmental anomalies. Insults to developing cerebellar hemispheres and the fourth ventricle are believed to be the cause of malformation. Our patient was born from noncomplicated pregnancy, noncomplicated nontraumatic vaginal delivery at term, excellent Apgar scores, without peculiarities in clinical status. She was brest-fed by the 42nd hour of life when she had rightsided seizures during sleep that repeated for five times in next 24 hours. Brain Ultrasound (US) revealed clot in left lateral ventricle, slight dilatation of left ventricle, both sided periventricular echodensity, ischemia, slight enlargement of forth ventricle and a bit smaller cerebellum. There was no visible flow through left transverse, superior sagittal and straight sinus. Magnetic Resonance (MRI) confirmed the finding and showed thrombosis of left and right transverse venous sinuses and confluence of sinuses. Electroencephalogram (EEG) showed leftsided focal changes. The newborn was treated with phenobarbiton for 8 days and had no convulsions during that period. All coagulation parameters, homocistein, lipoproteins (a) and D-dimers were normal. There were no mutations on FV R506Q, PT 20210A, MTHFR 677C/T. No antiphospholipides were found. Heart US showed no structural anomalies. No other patology or risk factors were present at the time. Before discharge, US showed hydrocephalus. Flow in affected sinuses was visible with color Doppler. MRI showed recanalization of affected sinuses, also hydrocephalus and presentation of Dandy Walker On EEG there was borderline finding. Due to progression of hydrocephalus ventriculo-peritoneal shunt was placed. In age of 1 year EEG was slower for age but without focus. Neurological development was normal for age. The question is whether this child had intrauterine insult and inception of Dandy Walker with further postnatal progress of thrombosis and evolution to full picture of Dandy Walker with hydrocephalus OR thrombosis that led to development of hydrocephalus and Dandy Walker malformation in this child were accidental coexistance.

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.

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.