[Treatment of encephalopathy by means of valproic acid with carglumic acid. Reply]. / Tratamiento de la encefalopatia inducida por acido valproico con acido carbaglumico. Replica.

TITLE: Tratamiento de la encefalopatia inducida por acido valproico con acido carbaglumico. Replica.

[Treatment of encephalopathy by means of valproic acid with carglumic acid: two case reports and a review of the literature]. / Tratamiento de la encefalopatia por acido valproico con acido carbaglumico: descripcion de dos casos y revision de la bibliografia.

INTRODUCTION: Valproic acid (VPA) is a drug mainly used to treat epilepsy. Hyperammonaemic encephalopathy due to VPA is a rare but serious complication. The mechanism by which VPA influences the increase in ammonia consists in blocking the urea cycle, thereby inhibiting N-acetylglutamate synthase and diminishing acetyl coenzyme A. Generally, the treatment employed has been to withdraw VPA and to administer arginine, carnitine, antibiotics, glucose and protein restriction. Previous experience with carglumic acid is limited to reports of isolated cases of paediatric patients. CASE REPORTS: We report the cases of two adult patients with encephalopathy due to VPA who were treated with carglumic acid, in addition to the conventional measures. Following treatment with the drug, ammonia levels can be seen to return to normal values. In one of the two cases, owing to the existence of another cause of encephalopathy, no clinical improvement was observed. CONCLUSIONS: From the biochemical point of view, treating encephalopathy due to VPA with carglumic acid is a logical step, as it reverses the blockage of the urea cycle conditioned by VPA. The mechanism proposed as being the one by which brain toxicity and, therefore, encephalopathy are produced is the passage of ammonia in the form of glutamine to the inside of the cell, which then returns to ammonia and glutamate in the mitochondria and leads to oxidative stress. Carglumic acid must be considered an important part of the treatment in adult patients with hyperammonaemic encephalopathy due to VPA, although a randomised clinical trial needs to be conducted with the drug in order to test its efficacy.

TITLE: Tratamiento de la encefalopatia por acido valproico con acido carbaglumico: descripcion de dos casos y revision de la bibliografia.Introduccion. El acido valproico (VPA) es un farmaco principalmente usado en la epilepsia. La encefalopatia hiperamoniemica por VPA es una complicacion grave e infrecuente. El mecanismo por el que el VPA influye en la elevacion del amonio es bloqueando el ciclo de la urea, inhibiendo la N-acetilglutamato sintasa y disminuyendo la acetil coenzima A. De forma general, el tratamiento que se ha empleado ha sido la suspension del VPA y la administracion de arginina, carnitina, antibioticos, glucosa y restriccion proteica. La experiencia con acido carbaglumico se limita a comunicaciones de casos aislados de pacientes pediatricos. Casos clinicos. Descripcion de dos casos de pacientes adultos con encefalopatia por VPA tratados, ademas de las medidas convencionales, con acido carbaglumico. Tras el tratamiento con el farmaco se aprecia una normalizacion de los niveles de amonio. En uno de los casos, al existir otra causa de encefalopatia, no se aprecio mejora clinica. Conclusiones. Desde el punto de vista bioquimico es logico tratar la encefalopatia por VPA con acido carbaglumico, ya que revierte el bloqueo del ciclo de la urea condicionado por el VPA. El mecanismo propuesto por el que se produce la toxicidad cerebral y, por tanto, la encefalopatia, es el paso de amonio en forma de glutamina al interior celular, que retorna a amonio y glutamato en la mitocondria y genera estres oxidativo. El acido carbaglumico ha de considerarse como parte importante del tratamiento en pacientes adultos con encefalopatia hiperamoniemica por VPA, aunque es necesario realizar un ensayo clinico aleatorizado con el farmaco para comprobar su eficacia.

Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals.

Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6%) patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4%) and 25 (5%) patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

[Striatal dopamine transporter density decrease in first episode schizophrenic patients treated with risperidone]. / Disminución del transportador de dopamina estriatal en primeros episodios psicóticos de pacientes esquizofrénicos tratados con risperidona.

UNLABELLED: Extrapyramidal symptoms and Parkinsonism (PS) are side effects commonly observed with antipsychotic treatment. However, about 24% of never-treated schizophrenic patients may suffer from PS, which contrast with that 1% observed from the general population. 123I-FP-CIT SPECT has probe useful to differentiate degenerative from non-degenerative PS, so it could be interesting using it for establishing the functional state of presynaptic dopamine neurons of these patients. AIM: To determine the dopamine transporter binding (DAT) in a homogeneous group of first-episode schizophrenic patients. METHODS: An open, transversal study. Thirty schizophrenic in-patients and 15 healthy subjects were recruited. Patients were treated with similar doses of risperidone and all subjects were scanned with 123I-FP-CIT. Extrapyramidal symptoms and psychopathological status was assessed by Simpson-Angus, CGI and PANSS. Semi-quantitative analyses of SPECT images were performed using ROIs placed in caudate nucleus, anterior, medium and posterior putamen and occipital cortex. RESULTS: Whole striatum 123I-FP-CIT binding ratio was significantly lower in patients than healthy subjects (t = 2.56, p < 0.014). This was observed in whole putamen (t = 2.66, p < 0.011), anterior (t = 2.35, p < 0.023), medium (t = 2.38, p < 0.022) and posterior putamen (t = 2.09, p < 0.042). No differences were observed in caudate nucleus (t = 1.81, p = 0.076). Females obtained higher binding ratios than males (t = -3.13, p < 0.003). No correlation was observed between 123I-FP-CIT binding ratios and clinical scales. CONCLUSION: In our series, first episode schizophrenic patients treated with risperidone have a decrease striatal DAT binding assessed with 123I-FP-CIT SPECT. This alteration could be related to their own schizophrenia disease or be secondary to the antipsychotic treatment.

Disminución del transportador de dopamina estriatal en primeros episodios psicóticos de pacientes esquizofrénicos tratados con risperidona / Striatal dopamine transporter density decrease in first episode schizophrenic patients treated with risperidone

El parkinsonismo (PS) es uno de los efectos secundarios más comunes de los fármacos antipsicóticos. Un 24 % de pacientes esquizofrénicos nunca tratados tienen PS, lo cual contrasta con el 1 % observado en la población normal. El 123I-FP-CIT podría determinar el estado funcional dopaminérgico presináptico de estos pacientes, ya que permite diferenciar PS degenerativo de no degenerativo.Objetivo. Evaluar la concentración del transportador de la dopamina (DAT) en un grupo homogéneo de pacientes jóvenes diagnosticados de esquizofrenia durante su primer episodio.Material y método. Estudio abierto, transversal. Se incluyeron 30 pacientes y 15 controles sanos. Los pacientes se trataron con dosis similares de risperidona y a todos los sujetos del estudio se les realizó una tomogammagrafía (SPECT) con 123I-FP-CIT. Se valoraron síntomas extrapiramidales y psicopatológicos mediante escalas Simpson-Angus, CGI y PANSS. El análisis de las imágenes de SPECT se realizó utilizando regiones de interés (ROI) en núcleos caudados, putamen anterior, medio, posterior y córtex occipital.Resultados. Los índices de captación global de 123I-FP-CIT fueron significativamente menores en pacientes esquizofrénicos que en sujetos sanos (t = 2,56; p < 0,014). Esta disminución significativa se apreció en todo el putamen (t = 2,66; p < 0,011), putamen anterior (t = 2,35; p < 0,023), medio (t = 2,38, p < 0,022) y posterior (t = 2,09; p < 0,042). No se observaron diferencias significativas en los núcleos caudados (t = 1,81; p = 0,076). Las mujeres obtuvieron índices de captación globales mayores que los hombres (t = ­3,13, p < 0,003). No se observó correlación entre la captación de 123I-FP-CIT y las diferentes escalas clínicas.Conclusión. En nuestra serie los pacientes esquizofrénicos con primer episodio psicótico tuvieron una disminución significativa de la captación estriatal del 123I-FP-CIT. Esta alteración podría ser debida a la propia enfermedad o ser secundaria al tratamiento antipsicótico

Extrapyramidal symptoms and Parkinsonism (PS) are side effects commonly observed with antipsychotic treatment. However, about 24 % of never-treated schizophrenic patients may suffer from PS, which contrast with that 1 % observed from the general population. 123I-FP-CIT SPECT has probe useful to differentiate degenerative from non-degenerative PS, so it could be interesting using it for establishing the functional state of presynaptic dopamine neurons of these patients.Aim. To determine the dopamine transporter binding (DAT) in a homogeneous group of first-episode schizophrenic patients.Methods. An open, transversal study. Thirty schizophrenic in-patients and 15 healthy subjects were recruited. Patients were treated with similar doses of risperidone and all subjects were scanned with 123I-FP-CIT. Extrapyramidal symptoms and psychopathological status was assessed by Simpson-Angus, CGI and PANSS. Semi-quantitative analyses of SPECT images were performed using ROIs placed in caudate nucleus, anterior, medium and posterior putamen and occipital cortex.Results. Whole striatum 123I-FP-CIT binding ratio was significantly lower in patients than healthy subjects (t = 2.56, p < 0.014). This was observed in whole putamen (t = 2.66, p < 0.011), anterior (t = 2.35, p < 0.023), medium (t = 2.38, p < 0.022) and posterior putamen (t = 2.09, p < 0.042). No differences were observed in caudate nucleus (t = 1.81, p = 0.076). Females obtained higher binding ratios than males (t = ­3.13, p < 0.003). No correlation was observed between 123I-FP-CIT binding ratios and clinical scales.Conclusion. In our series, first episode schizophrenic patients treated with risperidone have a decrease striatal DAT binding assessed with 123I-FP-CIT SPECT. This alteration could be related to the own schizophrenia disease or be secondary to the antipsychotic treatment

Successful treatment of rhinocerebral zygomycosis with a combination of caspofungin and liposomal amphotericin B.

Genera of the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella, and Saksenaea) cause an angioinvasive infection called zygomycosis. Mortality rates can approach 100% depending on the patient's underlying disease and form of zygomycosis. We report here on the unusual case of a patient with acute myelogenous leukemia and zygomycosis unresponsive to monotherapy with liposomal amphotericin B, who responded favorably following the addition of the echinocandin caspofungin acetate.

Accurate topographical diagnosis of urinary tract infection in male patients with (111)indium-labelled leukocyte scintigraphy.

Background: Although the clinical diagnosis of urinary tract infection (UTI) is straightforward, the precise localization of the urogenital organ affected by the infection is often difficult to establish. Methods: To evaluate this, we prospectively studied 20 males with a clinical diagnosis of acute pyelonephritis (APN), acute prostatitis (AP) and febrile UTI (FUTI), as well as seven control females with APN. (111)Indium-labelled leukocyte scintigraphy (ILS) was performed during the febrile episode and repeated when patients were free of symptoms. Results: ILS showed an abnormal uptake in a urinary organ in every case. All patients with AP showed uptake in the pelvic area. Four male patients presented AP, one of them had uptake in the lumbar area, one in the lumbar and pelvic area, and two in the area of the prostate only. Six out of seven patients with FUTI presented uptake in the pelvic area. All female patients showed kidney uptake. After the clinical resolution of the UTI, no residual uptake was found in any case except for one. Conclusions: These results suggest that ILS is very useful in localizing the affected organ in febrile UTI. Most male patients with a febrile UTI presented a prostatic involvement, suggesting that many cases of APN or FUTI in males may actually be cases of AP not recognized by standard clinical evaluation.

No brain perfusion impairment at long-term follow-up in elderly patients treated with electroconvulsive therapy for major depression.

No functional neuroimaging study has previously assessed the long-term effects of electroconvulsive therapy (ECT) on brain perfusion. In this study, long-term follow-up brain perfusion in elderly patients treated with ECT for severe unipolar major depression was assessed. In 14 elderly major depressed patients who were ECT remitters, 22 elderly major depressed patients who were pharmacological treatment remitters and 25 age- and sex-matched healthy controls, a medication-free brain 9mTc-HMPAO-SPECT was performed after a minimum period of 12 months of euthymia and, in the case of the ECT remitters, at least 12 months after the last ECT session. Brain perfusion ratios in major depressed patients administered ECT were similar to those in major depressed patients receiving pharmacological treatment and in control subjects. This result suggests that elderly patients given ECT for severe unipolar major depression do not suffer brain perfusion abnormalities at long-term follow-up. Our study adds new evidence in favor of the safety of the ECT, particularly in elderly subjects.

111Indium labelled leukocyte scintigraphy in the detection of acute prostatitis.

Although prostatitis is a common problem the diagnosis is still controversial despite the availability of a wide variety of diagnostic tools. In fact, there is still no accurate method of localizing the infected tissue. The aims of the present study were to assess whether 111In labelled leukocytes (ILLs) accumulated in the infected tissue of acute prostatitis and if such uptake responded to treatment. We prospectively studied 10 adult male patients who had community acquired prostatitis and compared them with six male patients who had urinary tract infections but without prostatitis. An initial urinary culture and two blood cultures were carried out for each patient. All patients were followed up for 8 weeks after therapy was completed. Pre- and post-treatment scintigraphies were performed. Before treatment, all patients with prostatitis showed uptake of ILLs in the prostate area. After the patients had completed treatment with antibiotics, the scintigraphy results showed no uptake in the prostate area in 9/10 patients. The remaining patient showed a marked decrease in the uptake of ILLs. None of the six patients with urinary tract infection showed ILL uptake in the prostate region. It is suggested that ILLs could be useful for detecting acute prostatitis, especially in clinically ambiguous patients with urological infections. Furthermore, scintigraphy with 111In labelled leukocytes could help to determine the most appropriate course of therapy.

[Fast method of labelling leukocytes with 99mTc HM PAO]. / Método rápido de marcaje de leucocitos con 99mTc HM-PAO.

OBJECTIVE: To modify the method of labelling leukocytes with 99mTc HM-PAO by centrifuging 15 minutes at low gravity (g) instead of sedimentation at a variable time (30-90 minutes) to obtain leukocytic rich plasma (LRP). METHODS: The g number recovering the greatest number of leukocytes was determined. The cellular composition of LRP obtained by centrifugation and sedimentation was analyzed. Lastly, labelling results in two groups of patients (p) were compared: one group of 118 p using the traditional sedimentation method (SM) and another of 124 p using the proposed centrifugation alternative (CM). RESULTS: Centrifugation at 5xg produced the greatest recovery of leukocytes (93.1 5.1%). No significant difference was observed in leukocyte recovery in LRP obtained either by centrifugation or by sedimentation. However, red blood cell contamination was greater in centrifugation (12.8 4.9 x 108) than in sedimentation (7.7 3.5 x 108) (p < 0.0001). The comparison of the SM and the CM gave the following results:The number of leukocytes recovered in both methods was similar (73.9 15.1% vs 76.5 12.7%) with approximately the same platelet contamination (8.0 6.2 vs 8.4 6.5%). The number of red blood cell contaminants per leukocyte was 3.0 1.0 for the MS and 5.1 2.6 for the MC (p < 0.001). Labelling yield (LY) was somewhat higher for the CM (57.8 11.9%) than for the SM (50.8 12.6%) as a result of greater red blood cell contamination and superior radiochemical purity of the 99mTc HM-PAO used in the labelling by CM (90,9 5,9%) with regard to the SM (87.9 9.5%). No difference was observed in the scintigraphic images obtained with either of the methods, given the scarce uptake of the radiopharmaceutical by the red blood cells (3-7%) in comparison with the leukocyte uptake (70-90%). CONCLUSION: The proposed MC considerably reduces the labelling time of leukocytes with 99mTc HM-PAO without affecting the quality of scintigraphic images and represents an important labelling alternative of great interest to the Radiopharmacy Units of Nuclear Medicine Services.

Could the hypofrontality pattern in schizophrenia be modified through neuropsychological rehabilitation?

OBJECTIVE: The effects of neuropsychological treatment on cognitive hypofrontality were examined in schizophrenic patients through the score activation. METHOD: Eight subjects (six men and two women) with persistent negative symptoms and cognitive impairments were evaluated with single photon emission computed tomography (SPECT) procedures and neuropsychological battery before and after a neuropsychological treatment group. RESULTS: After treatment an enhancement in neuropsychological performance was found, especially in executive functions. The activation score showed an increase over baseline levels and no cognitive-dependent hypofrontality after treatment was found. Although the prefrontal blood flow changes were small and non-specific, they suggest a reduction of the cognitive hypofrontality after neuropsychological treatment. CONCLUSION: Cognitive improvements after neuropsychological treatment would possibly be related with the diminution of the functional hypoactivity in the prefrontal areas.

Quantified 99mTc-MIBI scintigraphy for predicting chemotherapy response in breast cancer patients: factors that influence the level of 99m Tc-MIBI uptake.

The aim of this study was to establish whether tumour uptake of 99mTc-MIBI can predict response to chemotherapy in patients with breast carcinoma. Forty women suffering from breast carcinoma confirmed by tumour biopsy were studied prospectively. Fifteen patients subsequently underwent surgery and 25 were candidates for neoadjuvant chemotherapy. Breast scintigraphy was performed and planar and tomographic views (single photon emission computed tomography (SPECT)) were obtained after injection of 740 MBq of 99mTc-MIBI. The tumoural uptake was quantified by computer analysis. P-glycoprotein was evaluated by immunohistochemistry only in operable patients. The response to chemotherapy was evaluated at 3 months upon completion of treatment. The results of this study showed no relationship between 99mTc-MIBI uptake and the histological type or tumour size. There was an inverse correlation with the degree of tumour differentiation (P<0.05). 99mTc-MIBI uptake in negative P-glycoprotein lesions (2.36+/-1.72) was higher than in positive P-glycoprotein lesions (1.53+/-1.29), although the difference was not statistically significant. Lesions which responded to chemotherapy (16) showed higher 99mTc-MIBI uptake (7.70+/-5.20) than non-responding lesions (nine) (2.21+/-1.0) (P<0.001). In conclusion, there is a correlation between 99mTc-MIBI uptake in breast cancer and response to chemotherapy. Furthermore, 99mTc-MIBI uptake may be influenced by other factors such as the degree of tumour differentiation or tumour P-glycoprotein levels.

Frontal cerebral perfusion dysfunction in elderly late-onset major depression assessed by 99MTC-HMPAO SPECT.

Baseline regional cerebral blood flow of thirty unmedicated late-onset unipolar major depressed patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls was imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. To avoid errors of diagnosis--in particular, confusion between major depression and organic cognitive impairment--only treatment responders were included in the final sample. Statistically significant differences were observed in both left and right anterior frontal regions, with reduced uptake in depressed patients; these differences were more pronounced in the left hemisphere. Among patients, there was no correlation between regional cerebral blood flow and the severity of baseline symptoms. Our results support the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally involved in elderly unipolar major depression, particularly in the late-onset subgroup.

Salivary scintigraphy for assessing the protective effect of pilocarpine in head and neck irradiated tumours.

Patients with head and neck cancers can develop salivary hypofunction after radiotherapy. The use of pilocarpine during radiotherapy treatment has been shown to be an effective treatment, although its usefulness is being discussed. The aim of this study was: (1) to determine the value of a semiquantitative scintigraphy method for measuring the uptake and excretory salivary function of patients with head and neck irradiated tumours; and (2) to study the usefulness of pilocarpine as a salivary gland protector during radiotherapy. We prospectively studied 49 patients (mean age 61 years, range 29-87 years) with head and neck cancer in need of radiotherapy. Patients were divided into two groups consecutively: group P (26 patients) received 5 mg of pilocarpine three times per day starting the day before radiation therapy, and group NP (23 patients) received radiotherapy without pilocarpine and were used as the control group. Salivary gland scintigraphy and a visual analogue scale (VAS) of mouth dryness were obtained from each patient before radiotherapy and during the first year after treatment. The most frequent finding after radiotherapy was a quick impairment in parotid and submaxillary excretion (P < 0.001). There were no statistical differences comparing the pilocarpine group against the non-pilocarpine group. Parotid and submaxillary uptake significantly decreased after radiotherapy in both groups (P < 0.001). However, a tendency to recover within the pilocarpine group was observed in both the parotids and the submaxillary glands at 12 months. No differences were found comparing the VAS results in both groups. Strikingly, VAS data did not correlate with salivary gland dysfunction observed by means of scintigraphy. In conclusion, salivary scintigraphy is a useful technique to evaluate objectively the salivary gland function of patients with head and neck irradiated tumours as well as to test the response to pilocarpine. However, despite better results on the salivary uptake at 12 months, pilocarpine did not significantly improve salivary gland function.

Sentinel lymph node biopsy in breast cancer patients: subdermal versus peritumoural radiocolloid injection.

BACKGROUND AND AIMS: Sentinel lymph node (SLN) biopsy has been widely used in the management of melanoma and breast cancer. The aims of this study were (1) to compare the results obtained with the two main injection techniques, the peritumoural and subdermal; and (2) to determine the reliability of SLN to predict the regional lymph node status. METHOD: We prospectively studied 80 women (mean age 56 years) with breast cancer. Thirty-four of them were T1 and the remaining 46 were T2. Patients were divided into two groups. Group A, 36 patients were injected subdermally, surrounding the tumour site. Group B, 44 patients were injected peritumourally guided by ultrasound if non-palpable. Planar images were performed 15 min after the injection and continued until SLN identification. Before surgery, blue dye injection was administered similarly to the radiocolloid. After incision, a hand-held gamma probe was used to reach the SLN. All nodes harvested were analysed by classic pathology techniques. RESULTS: Overall, lymphoscintigraphy allowed the detection of SLN in 75/80 patients (94%). All subdermal lymphoscintigraphies were positive (36/36) compared with 89% of peritumoural (39/44). Blue dye detected SLN in 23/31 patients (74%) after subdermal injection and in 24/34 patients (71%) after peritumoural injection. The sensitivity to localize the SLN with lymphoscintigraphy+blue dye+gamma probe was 92% (33/36) within the subdermal group and 91% (40/44) within the peritumoural group. Overall, five false negative SLN were found. All of these corresponded to T2 tumours with a size greater than 2.5 cm. The negative predictive value and the accuracy were 93% and 94%, respectively, for the subdermal group and 90% and 93% for the peritumoural group. CONCLUSIONS: (1) Our results indicate that both techniques have similar results. However, we suggest that T2 tumours with a size greater than 2.5 cm should be excluded from the SLN technique, in order to improve the accuracy and negative predictive value. (2) Lymphoscintigraphy is essential for visualizing the SLN, and blue dye can be helpful when the gamma probe does not localize the SLN.