Glutamine and citrulline concentrations reflect nitric oxide synthesis in the human nervous system. / Las concentraciones de glutamina y citrulina reflejan la síntesis del óxido nítrico en el sistema nervioso humano.

INTRODUCTION: Although citrulline is produced by nitric oxide (NO) synthase upon activation of the NMDA glutamate receptor, nitrite and nitrate (NOx) concentration is considered the best marker of NO synthesis, as citrulline is also metabolised by other enzymes. This study analyses the correlation between human cerebrospinal fluid NOx and citrulline concentrations in order to determine the extent to which citrulline reflects NO synthesis and glutamatergic neurotransmission. METHODS: Participants were patients with acute neurological diseases undergoing lumbar puncture (n=240). NOx and amino acid concentrations were determined by HPLC. RESULTS: NOx concentrations did not vary significantly where infection (p=0,110) or inflammation (p=0,349) were present. Multiple regression analysis showed that NOx concentration was correlated with glutamine (r=-0,319, p<0,001) and citrulline concentrations (r=0,293, p=0,005) but not with the citrulline/arginine ratio (r=-0,160, p=0,173). ANCOVA confirmed that NOx concentration was correlated with citrulline concentration (F=7,6, p=0,007) but not with the citrulline/arginine ratio (F=2,2, p=0,136), or presence of infection (F=1,8, p=0,173) or inflammation (F=1,4, p=0,227). No association was found between NOx and arginine or glutamate concentrations. CONCLUSION: The results suggest that CSF citrulline concentration reflects NOx synthesis to some extent, despite the contribution of other metabolic pathways. In addition, this study shows that glutamine is an important modulator of NO synthase activity, and that arginine and glutamate are not correlated with NOx.

[An unusual presentation of painful tic convulsive]. / Presentacion inusual de un tic convulsivo doloroso.

INTRODUCTION: The term 'painful tic convulsive' is used to describe the syndrome involving concomitant hemifacial spasm and ipsilateral trigeminal neuralgia. Vascular compression of the fifth and seventh cranial nerves is the most common cause, involving the entry and exit zone of rootlets coming from the brainstem; nevertheless, different etiologies of this syndrome has been previously reported. Treatment for this disease is based on surgical microvascular decompression of the nerve rootlets, but still a topic of debate. CASE REPORT: A 63-year-old woman with history of 14 years presenting left trigeminal neuralgia, associated with ipsilateral hemifacial spasm for more than ten years. Medical treatment was installed without adequate symptom control. Patient was subjected to surgical treatment via a microasterional approach, with dissection of arachnoid fibrous tissue surrounding fifth and seventh nerves during the first surgery. A second surgery was performed with insertion of a teflon fragment aside of each exit nerve root (V and VII-VIII complex). Symptoms resolved immediately after the surgery and has persisted during the 1-year follow-up. Painful tic convulsive etiology could be multifactorial. CONCLUSION: This report is the first clinical case describing basal arachnoiditis as a primary cause of painful tic convulsive.

TITLE: Presentacion inusual de un tic convulsivo doloroso.Introduccion. La presentacion clinica de un espasmo hemifacial asociado a neuralgia trigeminal ipsilateral se conoce como tic convulsivo doloroso. La causa mas comun de esta patologia es la compresion vascular de los nervios craneales V y complejo VII-VIII en la zona de entrada y salida de las raices en el tronco del encefalo, pero existen informes de diversas etiologias. Su tratamiento, aunque aun esta en discusion, se basa en la descompresion microvascular quirurgica. Caso clinico. Mujer de 63 años, con un cuadro de evolucion de 14 años de neuralgia trigeminal, con predominio en distribucion de la rama maxilar (V2) izquierda, asociado durante mas de 10 años a espasmo hemifacial ipsilateral. Tras fallar el tratamiento medico, se sometio a cirugia por abordaje microasterional, y en un primer momento se realizo una diseccion de adherencias aracnoideas firmes rodeando complejos nerviosos. En un segundo tiempo quirurgico se insertaron fragmentos de teflon en los sitios de entrada de los nervios V y complejo VII-VIII, y se logro una resolucion completa de la sintomatologia durante mas de un año. Conclusion. La etiologia del tic convulsivo doloroso en esta paciente fue aracnoiditis basal, lo cual la convierte en el unico caso comunicado hasta el momento con dicha etiologia.

Relation of cerebrospinal fluid/plasma HIV-RNA discordance with neurocognitive impairment.

Neurological involvement is common in patients infected with HIV. The effectiveness of antiretroviral drugs in lowering the levels of HIV-RNA in cerebrospinal fluid (CSF) is limited by their inability to cross the blood-brain barrier. Discordance in CSF/plasma HIV-RNA levels may have a bearing on the progression of neurological disease in these patients. We report a woman with subacute neurocognitive impairment and abnormal findings on brain MRI, in whom there was a discordance between CSF/plasma HIV-RNA levels. The patient improved after a change in her highly active antiretroviral therapy (HAART) regimen. We also reviewed the available literature on the subject and found seven articles describing 27 patients.

Cryptococcoma of the brain in an immunocompetent man.

Cryptococcosis is a common opportunistic systemic disease in immunocompromised patients. Pulmonary or brain cryptococcosis is the most common clinical presentation. Immunocompetent patients can also be affected, especially in tropical and subtropical zones where the life cycle of the causal agent, Cryptococcus gattii, is completed. We present a previously healthy man with progressive intracranial hypertension and a right paraventricular mass on CT scan and MRI. Cryptococcus gattii yeasts were isolated from the cerebrospinal fluid. A ventriculoperitoneal shunt was placed and the patient was treated with amphotericin B, fluconazole and dexamethasone. The patient died due to severe intracranial hypertension.

Imbalance between nitric oxide and dopamine may underly aggression in acute neurological patients.

The neurochemical basis of aggressive behavior in humans is not fully understood. In this study we explored the relationship between aggressiveness (as measured by the Overt Aggression Scale), cognitive performance (as measured by the Mini Mental State Examination), and biochemical markers of dopamine neurotransmission (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO(x)) in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain infections. Aggressive behavior and cognitive performance showed an inverse correlation. NO(x)/HVA ratio was inversely correlated to aggressive behavior, and positively correlated to cognitive performance. A subanalysis with antipsychotic-naïve patients confirmed those results. The balance between nitric oxide and dopamine could be related to the cognitive control of aggressive impulse.

Albendazole trial at 15 or 30 mg/kg/day for subarachnoid and intraventricular cysticercosis.

Thirty-six patients with subarachnoid and intraventricular cysticercosis were randomly assigned to receive albendazole at 15 or 30 mg/kg/day plus dexamethasone for 8 days. Results favored a higher dose, with larger cyst reduction on MRI at 90 and 180 days and higher albendazole sulfoxide levels in plasma. An albendazole course at 30 mg/kg/day combined with corticosteroids is safe and more effective than the usual dose. A single treatment was insufficient in intraventricular and giant cysts.

[Frequency of neuropsychiatric signs and symptoms in patients with viral encephalitis]. / Frecuencia de signos y síntomas neuropsiquiátricos en pacientes con encefalitis viral.

INTRODUCTION: Acute viral encephalitis (AVE) is a frequent condition that usually courses with psychiatric alterations but few systematic studies have been conducted to investigate it. AIMS: To determine the frequency and the progression of the neuropsychiatric symptoms in patients with AVE. PATIENTS AND METHODS: A retrospective study was carried out. AVE was defined as an acute and progressively coursing condition in previously healthy subjects, with clinical signs of diffuse alteration of the central nervous system, abnormal electroencephalogram and/or inflammatory cerebrospinal fluid (CSF). We excluded patients who previously had epilepsy, a positive serodiagnosis for human immunodeficiency virus (HIV), and cases compatible with herpes simplex encephalitis from electroencephalographic or imaging data with focalisation towards temporal, frontal, regions or a positive DNA test for herpes in CSF. Finally, 83 patients were included. The psychiatric signs and symptoms that were produced were recorded during the acute phase and one year after discharge from hospital (sequelae). RESULTS: The psychiatric disorders in the acute phase were psychomotor agitation (67%), drowsiness (55%), disorientation (47%), visual hallucinations (43%) and aggressiveness (34%). One year after hospitalisation, in a sample of 70 patients in a clinical control, we found memory disorders (16%), aggressiveness (9%), aphasia (8%), visual hallucinations (8%), and auditory hallucinations (7%). The mortality rate was 6%. CONCLUSIONS: Neuropsychiatric disorders are very frequent during the acute phase of viral encephalitis, which is relevant for the differential diagnosis in patients who visit emergency departments with behavioural disorders. One year after hospital discharge, the main sequelae are of a neuropsychiatric nature and cognitive impairment is predominant.

Frecuencia de signos y síntomas neuropsiquiátricos en pacientes con encefalitis viral / Frequency of neuropsychiatric signs and symptoms in patients with viral encephalitis

Introducción. La encefalitis viral aguda (EVA) es un padecimiento frecuente que suele cursar con alteraciones psiquiátricas, que han sido estudiadas de forma sistemática. Objetivo. Conocer la frecuencia y la evolución de las manifestaciones neuropsiquiátricas en pacientes con EVA. Pacientes y métodos. Se ha realizado un estudio retrospectivo. Se definió la EVA como un padecimiento agudo y de curso progresivo en sujetos previamente sanos, con signos clínicos de alteración difusa del sistema nervioso central, electroencefalograma anormal y/o líquido cefalorraquídeo (LCR) inflamatorio. Excluimos a los pacientes con epilepsia previa o serología positiva para el virus de la inmunodeficiencia humana (VIH), y los casos compatibles con encefalitis herpética por datos electroencefalográficos o de imagen con focalización hacia las regiones temporales o frontales, o con prueba de ADN positiva para herpes en el LCR. Se incluyeron 83 pacientes. Se registraron los signos y síntomas psiquiátricos manifestados durante la fase aguda y un año después del alta hospitalaria (secuelas). Resultados. Las alteraciones psiquiátricas en la fase aguda fueron: agitación psicomotora (67%), somnolencia (55%), desorientación (47%), alucinaciones visuales (43%) y agresividad (34%). Un año después de la hospitalización, en 70 pacientes en control clínico, encontramos: alteraciones de la memoria (16%), agresividad (9%), afasia (8%), alucinaciones visuales (8%) y alucinaciones auditivas (7%). La mortalidad fue del 6%. Conclusiones. Las alteraciones neuropsiquiátricas son muy frecuentes durante la fase aguda de la encefalitis viral, lo que es relevante para el diagnóstico diferencial de los pacientes que acuden a los servicios de urgencias con alteraciones conductuales. A un año del alta, las principales secuelas son neuropsiquiátricas, y predomina el déficit cognitivo (AU)

Introduction. Acute viral encephalitis (AVE) is a frequent condition that usually courses with psychiatric alterations but few systematic studies have been conducted to investigate it. Aims. To determine the frequency and the progression of the neuropsychiatric symptoms in patients with AVE. Patients and methods. A retrospective study was carried out. AVE was defined as an acute and progressively coursing condition in previously healthy subjects, with clinical signs of diffuse alteration of the central nervous system, abnormal electroencephalogram and/or inflammatory cerebrospinal fluid (CSF). We excluded patients who previously had epilepsy, a positive serodiagnosis for human immunodeficiency virus (HIV), and cases compatible with herpes simplex encephalitis from electroencephalographic or imaging data with focalisation towards temporal, frontal, regions or a positive DNA test for herpes in CSF. Finally, 83 patients were included. The psychiatric signs and symptoms that were produced were recorded during the acute phase and one year after discharge from hospital (sequelae). Results. The psychiatric disorders in the acute phase were psychomotor agitation (67%), drowsiness (55%), disorientation (47%), visual hallucinations (43%) and aggressiveness (34%). One year after hospitalisation, in a sample of 70 patients in a clinical control, we found memory disorders (16%), aggressiveness (9%), aphasia (8%), visual hallucinations (8%), and auditory hallucinations (7%). The mortality rate was 6%. Conclusions. Neuropsychiatric disorders are very frequent during the acute phase of viral encephalitis, which is relevant for the differential diagnosis in patients who visit emergency departments with behavioural disorders. One year after hospital discharge, the main sequelae are of a neuropsychiatric nature and cognitive impairment is predominant (AU)

Simultaneous treatment of a pituitary adenoma and an internal carotid artery aneurysm through a supraorbital keyhole approach.

We describe a case in which an incidental left carotid aneurysm was found during the preoperative evaluation of a pituitary adenoma. After magnetic resonance imaging (MRI) and angiography delineated their characteristics, we chose to treat both lesions simultaneously through a left supraorbital keyhole approach. The aneurysm clipping was followed by intracapsular resection of the tumor that was identified later as a non-secretory adenoma. The postoperative course was uneventful. This case shows that in carefully selected patients it is possible to treat successfully concurrent conditions through a minimally invasive approach, with the well known advantages of low morbidity and a short hospital stay.

The clinical spectrum of neurological manifestations in AIDS patients in Mexico.

BACKGROUND: Neurological complications may be present clinically in up to 39% of patients infected with HIV or AIDS. Some reports have shown different profiles of neurological illness related to geographic variations and the population studied. METHODS: This retrospective study describes the neurological manifestations of patients with AIDS seen between 1990 and 1998 at a single neurological referral hospital in Mexico City. RESULTS: One hundred forty-nine patients were included, 133 males (89%) and 16 females (10.7%). The average age was 33.8 years (9 to 75 years). Upon admission, only 50 patients (33.6%) were known to be seropositive to HIV-1. In 75 patients (50.3%), the neurological illness was definitory of AIDS and also was its first recognized clinical manifestation. The most common infection problems were brain toxoplasmosis (32.2%), meningeal cryptococcosis (21.5%), tuberculosis (8.7%), and AIDS-dementia complex (8.7%). There were eight (5.4%) cases of ischemic cerebrovascular disease and four (2. 7%) neoplasms. Two primary brain lymphomas and single cases of astrocytoma and oligodendroglioma, progressive multifocal leukoencephalopathy (PML), aseptic meningitis, acute encephalitis, transverse myelitis, myopathy, and cranial neuropathy were also seen. CONCLUSION: In comparison with other studies of neurological complications of AIDS, opportunistic infections amenable to treatment in our population were more common. A high case fatality rate was observed, as was a large proportion of patients in whom the neurological illness was the first manifestation of HIV infection or AIDS due to denied, unknown, or unrecognized risk factors for HIV infection.

Candida albicans cerebral granulomas associated with a nonfunctional cerebrospinal fluid shunt: case report.

OBJECTIVE AND IMPORTANCE: We report an unusual case of basal ganglia granulomas caused by Candida albicans that surrounded the proximal segment of a nonfunctional cerebrospinal fluid shunt in a previously healthy patient. CLINICAL PRESENTATION: A 22-year-old woman had undergone ventriculoatrial cerebrospinal fluid shunt placement for posttraumatic hydrocephalus 3 years previously. One year later, a shunt revision was followed by wound dehiscence with local infection at the neck level. She received oral administration of antibiotics for 3 months until the wound closed. Twelve weeks before admission, the patient experienced pulmonary emboli. She received anticoagulants, and the distal segment of the shunt was removed. Five weeks after shunt removal, she presented with headache and left-sided hemiplegia caused by right basal ganglia inflammatory masses. INTERVENTION: A stereotactic brain biopsy was performed, and the shunt remnants were removed. Microscopically, the lesions were acutely and chronically inflamed. C. albicans grew in tissue and in shunt hardware cultures. The patient was treated with 1.1 g of intravenously administered amphotericin B and orally administered ketoconazole; she recovered completely. CONCLUSION: C. albicans brain granulomas occur rarely in immunocompetent patients. Despite the large size of the lesions and severe brain edema, the absence of an underlying disease contributed to complete resolution after shunt removal and antifungal therapy.

In vitro activity of moxifloxacin(BAY 12-8039) against respiratory tract pathogens from six Latin-American countries.

The in vitro antibacterial activity of moxifloxacin (BAY 12-8039) was evaluated against 636 isolates of respiratory tract pathogens. The isolates were collected from July 1997 to August 1998 in the frame of a multinational Latin American study. E-test strips calibrated to read moxifloxacin MIC ranges from 0.002 to 32 microg/ml were used in susceptibility testing. Weekly quality control tests in each laboratory ensured reproducibility. Laboratories from Argentina, Brazil, Chile, Colombia, Mexico and Uruguay participated. MIC(90) for moxifloxacin were as follows: Streptococcus pneumoniae (304 isolates) 0.25 microg/ml, Haemophilus influenzae (135 isolates) 0.125 microg/ ml, Streptococcus pyogenes (66 isolates) 0.25 microg/ml, Moraxella catarrhalis (62 isolates) 0. 25 microg/ml and methicillin-sensitive Staphylococcus aureus (69 isolates) 0.25 microg/ml. These results agreed with reports from other areas. Moxifloxacin showed excellent activity against respiratory pathogens from participant countries.

Cranial epidural empyema with osteomyelitis caused by actinomyces, CT, and MRI appearance.

Actinomycosis is an uncommon cause of intracranial infection. Epidural empyema represents about 6% of CNS actinomycotic lesions. A case of an epidural empyema with parietal bone osteomyelitis caused by Actinomyces israelii is presented. Relevant neuroimaging features were bone erosions and a multiloculated collection with annular contrast enhancing on CT. Postoperative MRI revealed extensive involvement of the neighbor dura, falx, and subdural space. MRI was crucial to follow-up the response to antibiotic treatment.

Transient hemifacial spasm associated with subarachnoid brainstem cysticercosis: a case report.

The authors present the case of a 69 year old woman who developed bladder incontinence and confusion. A CT scan showed severe hydrocephalus and calcifications, prompting a ventriculoperitoneal shunt placement. On the day after operation the patient presented left hemifacial spasm. MR revealed a subarachnoid cysticercus rostral to the pons, and surgical excision was proposed. She refused surgery and was placed on prednisone. Brainstem auditory responses were absent on the left side 2 months after shunting and were still abnormal 53 months later. The hemifacial spasm disappeared 3 months after shunt placement and has not recurred in 5 years of follow-up.

Effects of pentoxifylline or dexamethasone in combination with amphotericin B in experimental murine cerebral cryptococcosis: evidence of neuroexcitatory pathogenic mechanisms.

In a murine model of intracerebral infection by Cryptococcus neoformans the therapeutic effects of pentoxifylline or dexamethasone were studied alone and in combination with amphotericin B. Assessed parameters were mean survival time, brain histopathology index, amounts of glutamate and gamma-aminobutyric acid in the brain, and yeast CFU per brain. Survival increased significantly in mice treated with dexamethasone, amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline; the latter had significantly longer survival than other treated groups. Indices of histopathological damage were similar in all treated groups. In infected untreated mice, the amounts of glutamate in the brain were decreased, presumably by depletion. In mice treated with amphotericin B plus dexamethasone, glutamate levels returned to the range of control mice. No differences in the amounts of gamma-aminobutyric acid were found between control and treatment groups. Brain fungal counts were significantly lower in mice treated with amphotericin B, amphotericin B plus dexamethasone, and amphotericin B plus pentoxifylline than in untreated animals. In this model, pentoxifylline in combination with amphotericin B improved survival, decreasing the fungal burden, and has potential as adjuvant therapy in cerebral cryptococcosis.

Effects of prednisone on ventriculoperitoneal shunt function in hydrocephalus secondary to cysticercosis: a preliminary study.

In a prospective open study, 15 patients with hydrocephalus secondary to cysticercosis who required insertion of a ventriculoperitoneal (VP) shunt were treated with 50 mg of prednisone given orally three times a week. Treatment began in the 1st postoperative week, with isoniazid and pyridoxine administered daily as antituberculous chemoprophylaxis. The drug regimen was continued with close follow up for 24 months. Clinical status, Karnofsky performance status (KPS) scores, and postoperative course in the prednisone-treated group were compared with 30 control patients with hydrocephalus due to cysticercosis. The control patients were matched by age and sex, underwent surgical shunting in the same period, and were followed routinely by the neurosurgery staff. Lumbar cerebrospinal fluid (CSF) was studied in 2, 16, and 32 weeks postoperatively in the prednisone group. At 24-month follow up two (13%) of 15 patients in the prednisone group and 19 (60%) of 30 patients in the control group required surgical shunt revisions for symptomatic shunt obstruction (p=0.002). Follow-up studies of CSF performed at 32 weeks in the prednisone group revealed improvement of abnormal values with statistically significant differences for glucose (p<0.02). Serial imaging studies in the prednisone group revealed persistence of cysticercal cysts with no change in size. Mean initial KPS scores were similar in both groups. At the end of the follow-up period, the mean KPS score was significantly higher in the prednisone group (p=0.003). Prednisone and chemoprophylactic drugs were well tolerated. These results suggest that in selected patients with hydrocephalus secondary to cysticercosis, intermittent long-term prednisone therapy after VP shunting may reduce shunt malfunction and improve the functional status of the patients.

Predictive value of digital subtraction angiography in patients with tuberculous meningitis.

Digital subtraction angiography (DSA) was performed in 24 adults with tuberculous meningitis (TBM) and results were correlated with 24 admission and 16 follow-up CT examinations. 19 MRI studies and clinical outcome at a mean follow-up of 44 weeks. DSA was abnormal in 11 patients. Abnormal DSA was associated with advanced clinical stages of the Medical Research Council classification, admission CT with hydrocephalus or gyral cortical enhancement. MRI disclosed brain infarcts not seen on initial CT in 8 cases. Of seven patients who died, 4 had abnormal and 3 normal DSA. Among patients who survived, those with normal DSA had a better functional outcome by Karnofsky scores. During follow-up infarcts were evident in 16 patients. Abnormal DSA in relation to brain infarcts had a sensitivity of 0.56, specificity 0.75, positive predictive value 0.82 and negative predictive value 0.46. A single arteriogram does not predict the outcome in patients with TBM and its value is limited in the assessment of vascular complications of TBM. Angiography in TBM is justified only in specific clinical trials to assess new therapeutic modalities against infarcts.

Subarachnoid hemorrhage secondary to a ruptured inflammatory aneurysm: a possible manifestation of neurocysticercosis: case report.

We report a case of a 32-year-old man who presented with subarachnoid hemorrhage. As revealed by lumbar puncture, the cerebrospinal fluid had low glucose, high protein levels, and pleocytosis with 5% of eosinophils. Cultures were negative. Enzyme-linked immunosorbent assay and complement fixation reactions for cysticercosis in cerebrospinal fluid were positive. An angiogram revealed an aneurysm of the right anteroinferior cerebellar artery. At surgery, the aneurysm was found to be surrounded by thickened leptomeninges, which histologically presented dense inflammation and remains of Cysticercus. The aneurysm could not be clipped, and it was wrapped. Postoperatively, the patient had dizziness and right ear tinnitus. He received prednisone therapy on alternate days and subsequently received albendazole for subarachnoid cysticerci. At the 4-year follow-up, the patient was asymptomatic and had normal cerebrospinal fluid. Although we cannot rule out a congenital aneurysm, its location inside an area of severe arachnoiditis around a cysticercus suggests an inflammatory origin. This type of vascular lesion not reported before should be suspected in patients with chronic cysticercotic meningitis.