Successful Treatment of a Rare Cholesterol Homeostasis Disorder Due to CYP27A1 Gene Mutation with Chenodeoxycholic Acid Therapy.

Cerebrotendinous xanthomatosis (CTX) is a genetic disorder of the cholesterol metabolic pathway, most often associated with variants in the CYP27A1 gene. The dysregulation of cholesterol metabolism results in the accumulation of metabolites such as cholestanol, which has a predilection for neuronal tissue and tendons. The condition is treatable with chenodeoxycholic acid (CDCA), which halts the production of these metabolites. We present two adult brothers, without diagnosis, suffering from ataxia, general muscle weakness and cognitive deficits. Both brothers suffered from early onset cataracts, watery stools and thoracic kyphoscoliosis. Magnetic resonance imaging revealed hyperintense alterations in the central nervous system and intratendinous xanthomas in the Achilles tendons. A biochemical analysis showed elevated levels of cholestanol, lathosterol and 7-dehydrocholesterol. Their family history was negative for neurological and metabolic disorders. Genetic testing revealed a pathogenic CYP27A1 variant (c.1184+1G>A) in both brothers, confirming the diagnosis. The patients were started on CDCA therapy and have shown significant improvement at their follow-up examinations. Early diagnosis and treatment initiation in CTX patients is of great importance, as the significant reversal of disease progression can be achieved. For this reason, clinical genetic testing is necessary when it comes to patients with an onset of cataracts, chronic diarrhea, and neurological symptoms in early childhood.

Reuse of textile wastewater for dyeing cotton knitted fabric with hybrid treatment: Coagulation/sand filtration/UF/NF-RO.

The aim of this study was to investigate the usefulness of a membrane hybrid process for the treatment of real textile wastewater (TWW) and its potential reuse in the dyeing of cotton knitted fabric (DCF) process. To determine a suitable pretreatment, sand filtration, coagulation, and UF hollow fiber (UF-HF) were compared on a laboratory scale in terms of turbidity, color, and total organic carbon (TOC). Here, UF-HF provided the best removal results of 93.6%, 99.0%, and 29.0%, respectively. The second stage involves the study of UF flat sheet membranes (5, 10, 20, and 50 kDa). The 5 kDa membrane provided the best permeate quality according to the chemical oxygen demand (COD), turbidity, TOC, conductivity, and color by 54.5%, 83.9%, 94.2%, and 45.7-83.3%, respectively. The final step was treatment with nanofiltration (NF) and reverse osmosis (RO) and these effluents were reused for dyeing. Finally, the effluents from UF-HF/5 kDa UF/RO (Scenario 1) and UF-HF/5 kDa UF/NF (Scenario 2) were analyzed for turbidity, COD, TOC, biological oxygen demand, conductivity, hardness, anions and cations, and color. Both scenarios provided high removal results of 76.3-83.5%, 94.6-97.7%, 88.5-99%, 95.4-98.0%, 59.2-99.0%, 88.7-98.7%, 60.7-99.1%, and 80.0-100%, respectively. They also satisfied the DCF tests compared to the standard DCF samples. The innovative aspect of this research is as follows: 1) the complete analysis of hybrid membrane separation processes for the purpose of reuse of treated textile wastewater and 2) the proposal of a new criterion for reuse for DCF.

Epilepsy in patients with pineal gland cyst.

OBJECTIVE: The aim of the study is to describe types of epileptic seizures in patients with pineal gland cyst (PGC) and their outcome during follow up period (6-10 years). We wanted to determine whether patients with epilepsy differ in PGC volume and compression of the PGC on surrounding brain structures compared to patients with PGC, without epilepsy. PATIENTS AND METHODS: We analyzed prospectivelly 92 patients with PGC detected on magnetic resonance (MR) of the brain due to various neurological symptoms during the period 2006-2010. Data on described compression of the PGC on surrounding brain structures and size of the PGC were collected. RESULTS: 29 patients (16 women, 13 men), mean age 21.17 years had epilepsy and PGC (epilepsy group). 63 patients (44 women, 19 men), mean age 26.97 years had PGC without epilepsy (control group). Complex partial seizures were present in 8 patients, complex partial seizures with secondary generalization in 8 patients, generalized tonic clonic seizures (GTCS) in 10 and absance seizures in 3 patients. Mean PGC volume in epilepsy group was 855.93 mm3, in control group 651.59 mm3. There was no statistically significant difference between epilepsy and control group in PGC volume. Compression of PGC on surrounding brain structures was found in 3/29 patients (10.34%) in epilepsy group and in 11/63 patients (17.46%) in control group with no statistically significant difference between epilepsy and control group. All patients with epilepsy were put on antiepileptic therapy (AET). During the follow up period, 23 patients (79.31%) were seizure free, 3 patients (13.04%) had reduction in seizure frequency, whereas 3 patients had no improvement in seizure frequency. Two patients from epilepsy group and 3 patients from control group were operated with histologically confirmed diagnosis of PGC in 4, and pinealocytoma in 1 patient. CONCLUSIONS: In patients with PGC, epileptic seizures were classified as: complex partial seizures (with or without secondary generalization), GTCS and absance seizures. All patients were put on AET. During follow up period 79.31% patients were seizure free. There was no difference in PGC volume, nor in described compression of the PGC on surrounding brain structures between epilepsy and control group. Based on our findings, pathomechanism of epileptic seizures in patients with PGC cannot be attributable solely to PGC volume or described compression on surrounding brain structures based on MRI findings.

Visual evoked potentials in patients with pineal gland cyst.

AIMS: The functional effect of the pineal gland cyst is difficult to evaluate with visual field examination. The aim of this study is to investigate the usefulness of visual evoked potentials (VEP) in patients with pineal gland cyst due to the possible compression on the visual pathway. SUBJECTS AND METHODS: Black-and-white pattern-reversal checkerboard VEP were recorded in 75 patients (50 females and 25 males, mean age 26.3 ± 15.7 and 25.6 ± 17.6 years, respectively) with pineal gland cyst detected on magnetic resonance of the brain (subject group) and 75 age and sex-matched control subjects (control group). Amplitudes and P100 latencies were collected and later grouped as: (1) normal finding; (2) prechiasmal; (3) prechiasmal and postchiasmal; and (4) postchiasmal dysfunction. RESULTS: P100 latencies differed significantly between subject (110.26 ± 13.23 ms) and control group (101.01 ± 5.36 ms) (p < 0.01). Findings of the VEP differed significantly (p < 0.01) between subject and control group, mainly due to the postchiasmal dysfunction frequency in subject group. Findings of the VEP differed significantly according to the pineal gland cyst volume (p = 0.006) with more frequent postchiasmal dysfunctions among subjects with larger cysts. Postchiasmal changes were significantly more frequent in patients with described compression of the cyst on surrounding brain structures (p = 0.016). CONCLUSIONS: Postchiasmal dysfunction on VEP can be seen in patients with pineal gland cyst, mostly with larger cysts and with compression of the cyst on surrounding brain structures. VEP serve as a useful method to determine functional impairment of the visual pathway in patients with pineal gland cyst.

Diagnostic value of some less frequently considered blink reflex parameters in idiopathic trigeminal neuralgia.

AIM OF THE STUDY: We have done a study investigating the value of some less frequently considered Blink reflex parameters for establishing the diagnosis of idiopathic trigeminal neuralgia. PATIENTS: The study was done on 50 patients suffering from idiopathic trigeminal neuralgia, diagnosed according to the guidelines of the International Classification of Headache Disorders, with no other apparent illness. METHODS: We have stimulated the supraorbital nerve at the forehead (foramen n. supraorbitalis) and recorded the reflex response on both mm. orbiculares oculi. Incidence of following findings was determined: (1) occurrence of ipsilateral R3 component, (2) prolonged duration (>25 ms) of R2 when stimulating the affected side and (3) occurrence of R1 component during the stimulation of contralateral supraorbital nerve. We have compared these findings to those of 50 healthy subjects from the control group (Chi-square, p < 0.05). Sensitivity, specificity and diagnostic value for individual parameters were determined. RESULTS AND CONCLUSION: All three parameters tested proved to have a significantly higher incidence in the group of subjects. The occurrence of R3 component on the affected side showed the highest diagnostic value. SIGNIFICANCE: We believe these findings could electrophysiologically reinforce the clinically established diagnosis of idiopathic trigeminal neuralgia.

Moyamoya disease in a patient with brain tumor: case report.

A 40-year-old male presented to emergency room with epileptic grand mal seizure. He had untreated hypertension, and prior diagnostic investigation showed duplex renal arteries of the right kidney with hyperreninemia in the left renal vein. He was nonsmoker, with moderate alcohol intake. Neurologic examination was normal except for high blood pressure and tongue bite. Electroencephalogram was nonspecific. Nuclear magnetic resonance (NMR) showed vascular lesions in the white matter and infratentorially an expansive lesion with no postcontrast imbibition in the right cerebellar hemisphere. Neurosonography revealed hypoplasia of both internal carotid arteries (ICA), mean diameter <2 mm, subtotal stenosis at the origin of both ICA, and development of collateral path, typical for moyamoya disease. Magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) confirmed the neurosonography diagnosis. Immunologic tests for vasculitis were negative, while hematologic examination showed 4G allele for PAI-1. Serum lipids were elevated. We recommended neurosurgical operation of brain tumor. Histopathologic finding showed meningioma. This case is interesting because of the rare complex cerebrovascular disease, i.e. coexistence ofhypoplasia of both ICA, bilateral subtotal stenosis of ICA, intracranial moyamoya disease, and brain tumor.

Brainstem raphe lesion in patients with major depressive disorder and in patients with suicidal ideation recorded on transcranial sonography.

Recent transcranial sonography (TCS) studies showed that disruption of echogenic midbrain line, corresponding to basal limbic system and raphe nuclei (RN) within, might represent functional marker for the development of depression. Major depressive disorder (MDD) is one of the most common psychiatric disorders associated with suicidal ideation. We initiated this study to assess the usefulness of TCS recording in a group of MDD patients and in MDD patients who also reported suicidal ideation, on the assumption that TCS might serve as a screening method for differentiating patients at risk of suicide. Altogether 71 subjects: 17 patients with MDD, 14 patients with MDD who also reported suicidal ideation and 40 healthy controls, were studied using TCS by two independent physicians. Reduced raphe echogenicity was found in 8 of 17 (47%) of the patients with MDD but only in 6 of 40 (15%) controls. In patients with suicidal ideations that finding was even more pronounced (12 of 14, 86%) with the highest frequency of completely not visible TCS RN finding (10 of 14, 72%). Data showed that altered echogenicity of the RN is frequent in patients with suicidal ideation. Normal RN echogenicity in MDD patients was associated with less severe depressive symptoms and rarely with the presence of suicidal ideations. As far as we know, these are the first ever obtained results which show that TCS might help differentiating MDD patients with suicidal risk or eventually predict good disease recovery based on the findings of RN hypo- or normoechogenicity.

Median nerve imaging using high-resolution ultrasound in healthy subjects.

Although electroneuro- and electromyography are still the leading diagnostic methods for investigation of peripheral nerve function, they do not provide information on their morphology. This study was conducted to evaluate the suitability of ultrasonography in visualization of median nerve in healthy volunteers. Twenty-five asymptomatic volunteers (17 women and 8 men), age range 21-47 years, participated in the study. Body height was measured and handedness ascertained, as well as average time spent daily working on a computer. The device used was Aloka Prosound Alpha10 Premier with a 13-MHz probe, using custom preset for musculoskeletal sonography. The following dimensions of median nerve at the pisiform bone level were measured bilaterally: cross-sectional area (CSA), circumference, and longer and shorter diameter. Using the latter values, the flattening ratio (FR) was calculated. Median nerve and the surrounding soft tissue structures were easily depicted in all study subjects. The mean median nerve CSA was 9.70 mm2 (range 5-15 mm2, SD 2.25 mm2), mean FR (longer/shorter diameter) 4.04 (range 2.16-6.08), and median height 172.72 cm. Only one subject was left-handed. The mean time spent daily working on a computer (overall mean of 3.2 h/day) did not correlate with either CSA or FR for the dominant hand. In four subjects, an aberrant artery accompanying median nerve was visualized. High-resolution sonographic imaging is a fast and noninvasive method for assessment of various morphological properties of median nerve and can be used to enhance diagnostic efficiency.

Emergency EEG and diagnostic yield.

The aim of the study was to determine whether an acute loss of consciousness, mental status change or related symptoms correlated with the presence of epileptiform abnormalities on urgent EEG. We analyzed 228 consecutive patients admitted to Emergency Room during the past 12 months and referred for urgent EEG evaluation. All patients had either a brief loss of consciousness or acute brain disorder, with a clinical diagnosis of epilepsy, syncope, head trauma, headache, transient ischemic attack (TIA) or vertigo. Statistical analysis was performed using Spearman's rho test for group comparison and multivariate regression analysis. The mean age of patients was 48 +/- 20 years. The frequency of referring clinical diagnoses was as follows: epilepsy 44.7% (102/228), TIA 15.8% (36/228), syncope 15.4% (35/228), headache 11% (25/228), vertigo 7.9% (18/228) and acute head trauma 5.3% (12/228). EEG indicated epileptiform abnormalities in 14.9% (34/228) and focal slowing in 9.2% (21/228) of patients. The majority of them (26%; 21/81) had a clinical diagnosis of epilepsy. There was a significant correlation between clinical diagnosis of epilepsy and epileptiform EEG (Spearman's rho = 0.13; P < 0.04). Multivariate regression analysis showed that there was no predictive value in the clinical diagnosis of epilepsy and epileptiform EEG (beta = 1.483, P = 0.16). In conclusion, epilepsy was the most common clinical diagnosis in patients referred for urgent EEG. There was a significant correlation between the diagnosis and specific EEG abnormalities, however, the diagnosis of epilepsy failed to predict epileptiform activity on EEG. Study results suggested urgent EEG to have a high yield in patients with epilepsy.

Pineal gland cysts--an overview.

Pineal cysts occur in all ages, predominantly in adults in the fourth decade of life. In series of magnetic resonance imaging (MRI) studies, the prevalence of pineal cysts ranged between 1.3% and 4.3% of patients examined for various neurologic reasons and up to 10.8% of asymptomatic healthy volunteers. The diagnosis of pineal cyst is usually established by MRI with defined radiological criteria to distinguish benign pineal cyst from tumors of this area. A recent study demonstrated the findings obtained by transcranial sonography to correspond to those obtained by MRI in the detection of both pineal gland cyst and pineal gland itself, and could be used in the future mainly as follow up examination. Pineal cysts usually have no clinical implications and remain asymptomatic for years. The most common symptoms include headache, vertigo, visual and oculomotor disturbances, and obstructive hydrocephalus. Less frequently, patients present with ataxia, motor and sensory impairment, mental and emotional disturbances, epilepsy, circadian rhythm disturbances, hypothalamic dysfunction of precocious puberty, and recently described occurrence of secondary parkinsonism. Symptomatic cysts vary in size from 7 mm to 45 mm, whereas asymptomatic cysts are usually less than 10 mm in diameter, although a relationship between the cyst size and the onset of symptoms has been proved to be irrelevant in many cases. There is agreement that surgical intervention should be undertaken in patients presenting with hydrocephalus, progression of neurologic symptoms, or cyst enlargement. Tissue sample of the pineal lesion can be obtained by open surgery, stereotaxy and neuroendoscopy.

[Association of epilepsy and headache from the patient perspective]. / Povezanost epilepsija i glavobolje iz perspektive bolesnika.

Headache occurs more frequently in patients with epilepsy as compared to the general population. Current studies in patients with epilepsy and migraine show that this increased frequency is independent of the seizure type, etiology or age at onset. People with epilepsy are 2.4 times more likely to be diagnosed with migraine. In our study, we evaluated patients' attitudes toward comorbidity of epilepsy and all headache types. Study results showed a significant number of patients to have experienced headaches after being diagnosed with epilepsy, and some of them assumed it was a side effect of their antiepileptic drug. Based on these data, we propose a more detailed assessment of the history of epilepsy including questions on headache, and offer the epilepsy patient a newer antiepileptic drug. In this way, we can significantly decrease the comorbidity of these two neurologic disorders and improve the quality of life in epilepsy patients.

Prevalence of mood dysfunction in epilepsy patients in Croatia.

Fifty consecutive and consenting epilepsy patients from the Zagreb Epilepsy Center were examined for the presence of depressive symptoms using the Beck Depression Inventory (BDI). This questionnaire has been previously validated for use in the Croatian population. Mean age of the patients was 30.8 +/- 13.5 years, 60.4% were females. Majority of them were employed (72.9%) and single (62.5%), and 35.4% had a university degree. Most of them had complex partial seizures (n=40, 80%), and 6 (12%) were diagnosed with idiopathic generalized epilepsy. Assessment with the BDI showed that 33.3% of patients had recent depressive symptoms: 6.3% had mild depressive symptoms, 8.4% moderate and 18.6% severe depressive symptoms. Three patients (6.4%) attempted suicide in the past, two of them had current suicidal ideation, and all of them were severely depressed. This is the first and preliminary study assessing mood dysfunction in epilepsy patients in Croatia. Increased prevalence of depression in epilepsy patients suggests specific approach and need for early treatment.

Transcranial sonography in the evaluation of pineal lesions: two-year follow up study.

We have recently reported that transcranial sonography (TCS) is a method competitive to magnetic resonance neuroimaging (MRI) in the evaluation of pineal gland lesions. The aim of the present is study was to assess the usefulness of TCS in a larger patient sample during a two-year follow up. Twenty patients with incidental pineal gland cyst (PGC) detected by MRI scan of the brain and 40 healthy controls without any previous documented data on a disease related to pineal gland were evaluated by TCS and compared with MRI scans. There were no statistically significant differences in PGC size measured by TCS by two observers (p = 0.475), PGC size measured by TCS and MRI (first observer, p = 0.453; and second observer, p = 0.425), size of the pineal gland measured by TCS and MRI in control group (first observer, p = 0.497; and second observer, p = 0.370), and pineal gland size measured by TCS by two observers in control group (p = 0.473). Study results suggested TCS to be a suitable method in the evaluation of pineal gland lesions. Although its resolution cannot match the MRI resolution, its repeatability and accuracy might add to its practical value. We suggest that the repeat MRI scan of such lesions might be replaced by clinical and TCS follow up.

Effect of war on the occurrence of epileptic seizures in children.

We studied the occurrence of epileptic seizures in 72 children from war-affected and 39 children from non-war-affected areas during and after the 1991-1992 war in Croatia. During the war, children from war-affected areas who had "stable" epilepsy before the war and regularly took antiepilepsy medications had epileptic seizures more often than children from areas not affected by the war. In 2002, all children (n=10) whose first epileptic seizure was related to a stressful event had a "stable" condition, whereas 4 of 10 children whose first epileptic seizure was not stress-related had an "unstable" condition. Typical absence seizures were observed in 6 of 10 children in the stress-related group and none in the non-stress-related patient group. Stressful life events can be provocative factors for the occurrence of epileptic seizures. Typical absence seizures are more likely to be provoked by stress then other types of epileptic seizures.