Theoretical investigation of a novel xylene-based light-driven unidirectional molecular motor.

In this study, the working mechanism of the first light-driven rotary molecular motors used to control an eight-base-pair DNA hairpin has been investigated. In particular, this linker was reported to have promising photophysical properties under physiological conditions, which motivated our work at the quantum mechanical level. Cis-trans isomerization is triggered by photon absorption at wavelengths ranging 300 nm-400 nm, promoting the rotor to the first excited state, and it is mediated by an energy-accessible conical intersection from which the ground state is reached back. The interconversion between the resulting unstable isomer and its stable form occurs at physiological conditions in the ground state and is thermally activated. Here, we compare three theoretical frameworks, generally used in the quantum description of medium-size chemical systems: Linear-Response Time-Dependent Density Functional Theory (LR-TDDFT), Spin-Flip TDDFT (SF-TDDFT), and multistate complete active space second-order perturbation theory on state-averaged complete active space self consistent field wavefunctions (MS-CASPT2//SA-CASSCF). In particular, we show the importance of resorting to a multireference approach to study the rotational cycle of light-driven molecular motors due to the occurrence of geometries described by several configurations. We also assess the accuracy and computational cost of the SF-TDDFT method when compared to MS-CASPT2 and LR-TDDFT.

Tamoxifen-independent recombination of reporter genes limits lineage tracing and mosaic analysis using CreERT2 lines.

The CreERT2/loxP system is widely used to induce conditional gene deletion in mice. One of the main advantages of the system is that Cre-mediated recombination can be controlled in time through Tamoxifen administration. This has allowed researchers to study the function of embryonic lethal genes at later developmental timepoints. In addition, CreERT2 mouse lines are commonly used in combination with reporter genes for lineage tracing and mosaic analysis. In order for these experiments to be reliable, it is crucial that the cell labeling approach only marks the desired cell population and their progeny, as unfaithful expression of reporter genes in other cell types or even unintended labeling of the correct cell population at an undesired time point could lead to wrong conclusions. Here we report that all CreERT2 mouse lines that we have studied exhibit a certain degree of Tamoxifen-independent, basal, Cre activity. Using Ai14 and Ai3, two commonly used fluorescent reporter genes, we show that those basal Cre activity levels are sufficient to label a significant amount of cells in a variety of tissues during embryogenesis, postnatal development and adulthood. This unintended labelling of cells imposes a serious problem for lineage tracing and mosaic analysis experiments. Importantly, however, we find that reporter constructs differ greatly in their susceptibility to basal CreERT2 activity. While Ai14 and Ai3 easily recombine under basal CreERT2 activity levels, mTmG and R26R-EYFP rarely become activated under these conditions and are therefore better suited for cell tracking experiments.

Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy.

BACKGROUND AND PURPOSE: Progressive multifocal leucoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) is the paradoxical worsening or unmasking of preexisting infection with JC virus attributable to a rapid recovery of the immune system after highly active antiretroviral therapy (HAART) initiation. We investigated the incidence and factors associated with PML-IRIS in HIV-infected patients. We also studied its influence on mortality of PML and the effect of corticosteroid therapy. METHODS: Single-center retrospective analysis of HIV-infected patients diagnosed with PML from 1996 to 2012 who received HAART. RESULTS: Among 59 PML patients treated with HAART, 18 (30.51%) developed PML-IRIS (five delayed PML-IRIS, 13 simultaneous PML-IRIS). Patients who developed IRIS had lower CD4 counts prior to treatment (102 vs. 68.5, P < 0.05) and experienced a greater decline in HIV-RNA levels in response to HAART (2.5log vs. 2.95log, P < 0.05). Gadolinium enhancement on MRI was observed in 31.25% of PML-IRIS cases versus 2.56% of PML non-IRIS (P < 0.01). Survival rates were higher in patients with PML-IRIS compared to those with PML non-IRIS. Eight patients received corticosteroids, five of which had a good outcome. Patients who died were severely ill when treatment was initiated whereas patients who survived were treated before major neurological deterioration occurred. CONCLUSIONS: Nearly one-third of HIV-infected patients with PML develop IRIS after initiating HAART. Patients severely immunocompromised who experience a rapid virological response to HAART have a higher risk for PML-IRIS. There was a trend for lower mortality in patients with IRIS. Early treatment with corticosteroids might be useful.

Central nervous system involvement in adult patients with invasive infection caused by Streptococcus agalactiae.

INTRODUCTION: Streptococcus agalactiae is frequently an asymptomatic coloniser and a cause of neonatal and puerperal sepsis. Infections in nonpregnant adults are uncommon. The frequency of neurological complications caused by invasive infection with this microorganism in adults remains unknown. Here, we study the frequency and characteristics of central nervous system (CNS) involvement in adults with invasive S. agalactiae infection. PATIENTS AND METHODS: Review of all adults with invasive S. agalactiae infection between 2003 and 2011 in a tertiary hospital. RESULTS: S. agalactiae was isolated from blood, CSF or synovial fluid in 75 patients. Among them, 7 (9,3%) displayed neurological involvement: 5 men and 2 nonpregnant women, aged between 20 and 62 years. Diagnoses were spinal epidural abscess due to spondylodiscitis with spinal cord compression; acute bacterial meningitis; ischemic stroke as presentation of bacterial endocarditis (2 patients each); and meningoventriculitis after neurosurgery and ventricular shunting. One patient with endocarditis caused by S. agalactiae and S. aureus died in the acute phase, and another died 3 months later from metastatic cancer. The other patients recovered without sequelae. All patients had systemic predisposing factors for infection and 5 (71,4%) had experienced disruption of the mucocutaneous barrier as a possible origin of the infection. CONCLUSIONS: CNS involvement is not uncommon in adult patients with invasive infection caused by S. agalactiae. Isolating S. agalactiae, especially in cases of meningitis, should lead doctors to search for predisposing systemic disease and causes of mucocutaneous barrier disruption.

Continued declining incidence and improved survival of progressive multifocal leukoencephalopathy in HIV/AIDS patients in the current era.

To evaluate the situation and perspectives of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected patients, we investigated changes in the incidence, causes, and long-term outcome of this disease in 72 acquired immunodeficiency syndrome (AIDS) patients who were diagnosed with PML from 1996 to 2011. Patients were classified according to the date of diagnosis in the first (1996-2000, n = 35), second (2001-2006, n = 26), and recent or third highly active antiretroviral therapy (HAART) period (2007-2011, n = 11). Overall, the incidence of PML decreased from 14.8 cases/1,000 patients/year in 1996 to 2.6 in 2005 and 0.8 in 2011, and nearly two-thirds of recent cases (64 %) were observed in HIV patients not attending clinical visits. The baseline median CD4+ count was higher in recently PML-diagnosed patients (77 vs. 86 vs. 101 cells/mm(3); p < 0.01), and this fact was associated with a cerebrospinal fluid (CSF) inflammatory profile (from 11 to 31 to 55 %, p = 0.007) and with a significantly longer survival (attributable death, 54 vs. 35 vs. 36 %, respectively, p < 0.01). Thus, the overall 1-year and 3-year survival rates were 55 and 50 %, respectively, increasing to 79 % at 1 year for patients with CD4+ count above 100 cells/mm(3) at diagnosis. In a Cox regression analysis, an older age (hazard ratio, HR 0.76), a baseline CD4+ count above 100 cells/mm(3) (HR 0.33), and a CSF inflammatory profile (HR 0.12) were significantly associated with a longer survival. The clinical presentation and outcome of PML in AIDS patients continue to change dramatically. Now, a declining incidence and long-term survival is observed.

Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies.

BACKGROUND: Herpetic (HE) and autoimmune (AE) encephalitis share clinical and radiological features. We compared both types of encephalitis with the aim of making a differential clinical-radiological pattern. MATERIALS AND METHODS: All cases with a clinical diagnosis of encephalitis who attended our hospital between 1999 and 2012 were reviewed. We selected those cases with positive polymerase chain reaction for herpes simplex virus 1 (HSV-1) in the cerebrospinal fluid (CSF), and those with antineuronal antibodies or paraneoplastic etiology. We compared epidemiological, clinical, CSF, electroencephalographic and radiological findings. RESULTS: Twelve patients with positive polymerase chain reaction for HSV-1, and 10 patients with antineuronal antibody or paraneoplastic etiology were found. The only features found exclusively in one group were the presence of psychiatric symptoms and tumors in AE. Acute onset of symptoms, fever and aphasia were more frequent in HE, which showed higher level of proteins and erythrocyte count in CSF. Neuroimaging was abnormal in all cases of HE, but only in 60% of AE. Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement were more frequent in HE, and mesial temporal involvement in AE. The highest diagnostic values for differentiating HE from AE were the association of acute onset of symptoms and fever (sensitivity 0.92, specificity 1), and the absence of basal ganglia involvement (sensitivity 0.82, specificity 1). CONCLUSIONS: There are few differences between HE and AE. Psychiatric symptoms and association with tumors were unique for AE. Acute onset with fever and absence of basal ganglia involvement in magnetic resonance imaging support a diagnosis of HE.

Spinal cord infarction: aetiology, imaging findings, and prognostic factors in a series of 41 patients.

INTRODUCTION: Spinal cord infarction is a rare disease with a high rate of morbidity. Its diagnosis can be challenging and controversy remains regarding the best treatment. Few case series have been published. METHODS: We conducted a retrospective review of cases of spinal cord infarction attended in a tertiary hospital from 1999 to 2020. Aetiology and clinical, imaging, and prognostic features were assessed. RESULTS: Forty-one patients (58.5% men, mean [standard deviation] age 61 [17] years) were included in the study. Thirty-one patients (75.6%) presented vascular risk factors. Motor deficits were recorded in 39 (95.1%), pain in 20 (48.8%), sensory deficits in 33 (80.4%), and autonomic dysfunction in 24 (58.5%). MRI was performed in 37 (90.2%) patients. Diffusion-weighted images were available for 12 patients, with 10 showing diffusion restriction. The thoracic region was the most frequently affected (68.2%). Vascular imaging studies were performed in 33 patients (80.4%). The most frequent aetiologies were aortic dissection (6 cases), atherosclerosis demonstrated by vascular imaging (6 cases), fibrocartilaginous embolism (6 cases), surgery (5 cases), and hypotension (4 cases). Aetiology was undetermined in 12 patients (29.3%), although 9 of these presented vascular risk factors. At the end of the follow-up period (median, 24 months; interquartile range, 3-70), 12 patients (29.2%) were able to walk without assistance. Vascular risk factors and paraparesis were significantly associated with poorer prognosis (P < .05). DISCUSSION: Spinal cord infarction may present diverse aetiologies, with the cause remaining undetermined in many patients. Long-term functional prognosis is poor, and depends on baseline characteristics and clinical presentation. MRI, and especially diffusion-weighted sequences, is useful for early diagnosis.

Spinal cord infarction: aetiology, imaging findings, and prognostic factors in a series of 41 patients. / Infarto medular: etiología, hallazgos radiológicos y factores pronósticos en una serie de 41 pacientes.

INTRODUCTION: Spinal cord infarction is a rare disease with a high rate of morbidity. Its diagnosis can be challenging and controversy remains regarding the best treatment. Few case series have been published. METHODS: We conducted a retrospective review of cases of spinal cord infarction attended in a tertiary hospital from 1999 to 2020. Aetiology and clinical, imaging, and prognostic features were assessed. RESULTS: Forty-one patients (58.5% men, mean [standard deviation] age 61 [17] years) were included in the study. Thirty-one patients (75.6%) presented vascular risk factors. Motor deficits were recorded in 39 (95.1%), pain in 20 (48.8%), sensory deficits in 33 (80.4%), and autonomic dysfunction in 24 (58.5%). MRI was performed in 37 (90.2%) patients. Diffusion-weighted images were available for 12 patients, with 10 showing diffusion restriction. The thoracic region was the most frequently affected (68.2%). Vascular imaging studies were performed in 33 patients (80.4%). The most frequent aetiologies were aortic dissection (6 cases), atherosclerosis demonstrated by vascular imaging (6 cases), fibrocartilaginous embolism (6 cases), surgery (5 cases), and hypotension (4 cases). Aetiology was undetermined in 12 patients (29.3%), although 9 of these presented vascular risk factors. At the end of the follow-up period (median, 24 months; interquartile range, 3-70), 12 patients (29.2%) were able to walk without assistance. Vascular risk factors and paraparesis were significantly associated with poorer prognosis (P<.05). DISCUSSION: Spinal cord infarction may present diverse aetiologies, with the cause remaining undetermined in many patients. Long-term functional prognosis is poor, and depends on baseline characteristics and clinical presentation. MRI, and especially diffusion-weighted sequences, is useful for early diagnosis.

COVID-19 in Parkinson's disease: what holds the key?

INTRODUCTION: Parkinson's disease (PD) is more frequent in the elderly and increases the risk of respiratory infections. Previous data on PD and SARS-CoV-2 are scarce, suggesting a poor prognosis in advanced disease and second-line therapies. METHODS: A retrospective case-control study comparing patients with PD and COVID-19 and patients with PD without COVID-19 was conducted during the pandemic period in Spain (March 1st-July 31st 2020) in a tertiary university hospital. RESULTS: Thirty-nine (COVID-19 +) and 172 (COVID-19-) PD patients were included. Fifty-nine percent were males in both groups, with similar age (75.9 ± 9.0 COVID-19 + , 73.9 ± 10.0 COVID-19-), disease duration (8.9 ± 6.2 COVID-19 + , 8.5 ± 5.6 COVID-19-) and PD treatments. COVID-19 was mild in 10 (26%), required admission in 21 (54%) and caused death in 8 (21%) patients. Dementia was the only comorbidity more frequent in COVID-19 + patients (36% vs. 14%, p = 0.0013). However, in a multivariate analysis, institutionalization was the only variable associated with COVID-19 + (OR 17.0, 95% CI 5.0-60.0, p < 0.001). When considering severe COVID-19 (admission or death) vs. mild or absent COVID-19, institutionalization, neoplasm, dementia and a lower frequency of dopamine agonists were associated with severe COVID-19. In multivariate analysis, only institutionalization [OR 5.17, 95% CI 1.57-17, p = 0.004] and neoplasm [OR 8.0, 95%CI 1.27-49.8, p = 0.027] remained significantly associated. CONCLUSION: In our experience, institutionalization and oncologic comorbidity, rather than PD-related variables, increased the risk of developing COVID-19, and impacted on its severity. These findings suggest that epidemiologic factors and frailty are key factors for COVID-19 morbidity/mortality in PD. Appropriate preventive strategies should be implemented in institutionalized patients to prevent infection and improve prognosis.

3D Printing in Medicine for Preoperative Surgical Planning: A Review.

The aim of this paper is to review the recent evolution of additive manufacturing (AM) within the medical field of preoperative surgical planning. The discussion begins with an overview of the different techniques, pointing out their advantages and disadvantages as well as an in-depth comparison of different characteristics of the printed parts. Then, the state-of-the-art with respect to preoperative surgical planning is presented. On the one hand, different surgical planning prototypes manufactured by several AM technologies are described. On the other hand, materials used for mimicking different living tissues are explored by focusing on the material properties: elastic modulus, hardness, etc. As a result, doctors can practice before performing surgery and thereby reduce the time needed for the operation. The subject of patient education is also introduced. A thorough review of the process that is required to obtain 3D printed surgical planning prototypes, which is based on different stages, is then carried out. Finally, the ethical issues associated with 3D printing in medicine are discussed, along with its future perspectives. Overall, this is important for improving the outcome of the surgery, since doctors will be able to visualize the affected organs and even to practice surgery before performing it.

3D printed soft surgical planning prototype for a biliary tract rhabdomyosarcoma.

Biliary tract rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor which is located in the biliary tract. Although this tumor represents less than 1% of the total amount of childhood cancers, when localized, a >70% overall 5-year survival rate, the resection is clinically challenging and complications might exist during the biliary obstruction. Although surgery remains a mainstay, complete tumor resection is generally difficult to achieve without mutilation and severe long-term sequelae. Therefore, manufacturing multi-material 3D surgical planning prototypes of the case provides a great opportunity for surgeons to learn beforehand what they can expect. Additionally, practicing before the operation enhances the probability of success. That is why different compositions of materials have been characterized to match the mechanical properties of the liver. To do this, Dynamic Mechanical Analysis (DMA) tests and Shore hardness tests have been carried out. Amongst the material samples produced, 6%wt PVA (poly vinyl alcohol)/1%wt PHY (Phytagel)-1FT (Freeze-Thaw cycles) and 1%wt agarose appear as the best options for mimicking the liver tissue in terms of viscoelasticity. Regarding the Shore hardness, the best solution is 1%wt agarose. Additionally, a surgical planning prototype using this last material mentioned was manufactured and validated using a CT (Computed Tomography) scanner. In most of the structures the difference between the 3D model and the organ in terms of dimensions is less than 3.35 mm, which represents a low dimensional error, around 1%. On the other hand, the total manufacturing cost of the 3D physical model was €513 which is relatively low in comparison with other technologies.

Forty years of Tuberculous meningitis: The new face of an old enemy.

BACKGROUND: Tuberculous meningitis (TBM) occurs in 1-5% of cases of tuberculosis. Without early treatment, mortality and permanent disability rates are high. METHODS: A retrospective study performed at a tertiary hospital in Madrid (Spain) to describe clinical, diagnostic, and therapeutic aspects of TBM and analyze epidemiological trends over forty years, divided into two intervals (1979-1998 and 1999-2018). RESULTS: Overall, TBM was diagnosed in 65 patients (1.8% of new tuberculosis diagnoses), 48 in the first period and 17 in the second one. Median age at diagnosis increased from 38.5 to 77 years (p = 0.003). The proportion of non-HIV immunosuppressed patients increased (from 2.1% to 29.4%, p < 0.001), while the percentage of patients with a history of drug-abuse decreased (from 33.3% to 5.9%, p = 0.027). The median time between the onset of neurological symptoms and lumbar puncture increased from seven to 15 days (p = 0.040). The time between the onset of symptoms and the initiation of tuberculostatic treatment also increased from eleven to 18 days (p = 0.555). Results from image, biochemical, and microbiological tests showed no differences between both periods. A decreasing trend was observed in survival rates at 1-week (from 97.9% to 64.7%, p < 0.001), 1-month (from 91.7% to 58.8%, p = 0.002) and 1-year (from 85.4% to 47.1%, p = 0.002) after TBM diagnosis. CONCLUSIONS: The profile of patients diagnosed with TBM has changed from a young HIV-infected patient with a history of drug addiction to an elderly patient with non-HIV immunosuppression. Diagnosis and start of treatment both experienced a noticeable delay in the second period, which could help explain the increase in mortality observed across the two periods.

[Acute global amnesia as an exclusive presenting symptom of thalamic infarct: a diagnostic challenge]. / Amnesia global aguda como forma exclusiva de presentacion de infarto talamico: un reto diagnostico.

INTRODUCTION: Isolated acute amnesia is an exceptional presenting symptom of thalamic stroke. This study analyses the clinical profile, the diagnosis, the treatment and the prognosis of these patients. CASE REPORTS: We conducted a retrospective review of the cases of thalamic infarct that presented exclusively as acute amnesia in our university tertiary hospital (n = 3) and a review of similar cases in PubMed (n = 20). 48% presented at least one risk factor of stroke (arterial hypertension, dyslipidaemia, diabetes mellitus, atrial fibrillation or a previous stroke). Amnesia was anterograde in three cases (13%) and global in the remaining 20 (87%). The infarct was detected in neuroimaging studies carried out within the first 24 hours in one patient (4%) and later in all the others; the average time until a diagnosis was established was 11 days. The initial CT scan was normal in five patients (22%). Eight cases (35%) required magnetic resonance imaging to detect the infarct. Of these, four subjects were studied directly with MR imaging. Amnesia clearly improved in eight patients (35%), and three of them (13%) made a full recovery. Fifteen patients (65%) presented mnemonic sequelae that interfered with their functional capacity. The clinical picture lasted less than 24 hours in two patients (9%). None of the cases received revasculisation therapy in the acute phase. CONCLUSION: The diagnosis of thalamic infarcts that begin exclusively with amnesia is very difficult and this has negative repercussions on their treatment in the acute phase. These infarcts can produce a functionally disabling memory deficit in a high percentage of patients.

TITLE: Amnesia global aguda como forma exclusiva de presentacion de infarto talamico: un reto diagnostico.Introduccion. La amnesia aguda aislada es una forma excepcional de presentacion del ictus talamico. Se analizan el perfil clinico, el diagnostico, el tratamiento y el pronostico de estos pacientes. Casos clinicos. Revision retrospectiva de los casos de infarto talamico que se presentaron exclusivamente como amnesia aguda en nuestro hospital terciario universitario (n = 3) y revision de casos similares en PubMed (n = 20). El 48% presentaba al menos un factor de riesgo de ictus (hipertension arterial, dislipidemia, diabetes mellitus, fibrilacion auricular o ictus previo). La amnesia fue anterograda en tres casos (13%) y global en los otros 20 (87%). El infarto se detecto en estudio de neuroimagen en las primeras 24 horas en un paciente (4%) y posteriormente en los demas, y la media de dias hasta el diagnostico fue de 11. La tomografia computarizada inicial fue normal en cinco (22%) pacientes. Precisaron estudio por resonancia magnetica ocho (35%) casos para detectar el infarto. De estos, cuatro sujetos se estudiaron directamente con resonancia magnetica. La amnesia presento una mejoria clara en ocho (35%) pacientes, y la recuperacion fue completa en tres (13%). Las secuelas mnesicas que interferian la capacidad funcional se presentaron en 15 pacientes (65%). La clinica persistio menos de 24 horas en dos pacientes (9%). Ningun caso recibio tratamiento revascularizador en fase aguda. Conclusion. Los infartos talamicos que comienzan de forma exclusiva con amnesia presentan notables dificultades diagnosticas que repercuten negativamente en su tratamiento en la fase aguda. Estos infartos pueden producir un deficit mnesico funcionalmente discapacitante en un porcentaje elevado de pacientes.

[Occipital condyle syndrome as the first symptom of a metastatic hepatocellular carcinoma. Two case reports]. / Sindrome del condilo occipital como primera manifestacion de un carcinoma hepatocelular metastasico. Presentacion de dos casos.

INTRODUCTION: Occipital condyle syndrome consists of the presence of unilateral occipital headache exacerbated by moving the head and is accompanied by paralysis of the ipsilateral hypoglossal nerve. One of its causes is infiltration of the base of the skull by bone metastases, especially those affecting the hypoglossal nerve due to infiltration as it passes through the osseous canal. CASE REPORTS: We report two clinical cases of occipital condyle syndrome secondary to metastatic hepatocarcinoma. The first is that of a 52-year-old male with liver cirrhosis secondary to liver pathology caused by hepatitis C virus with occipital condyle syndrome as the presenting symptom in disseminated hepatocarcinoma. The second case is that of a 56-year-old male after recurrence of hepatocarcinoma following a liver transplant, despite not fulfilling the Milan criteria. CONCLUSION: Occipital condyle syndrome is an alarm symptom and requires a thorough study by means of imaging tests, since it may be the first symptom of an undetected hepatocarcinoma.

TITLE: Sindrome del condilo occipital como primera manifestacion de un carcinoma hepatocelular metastasico. Presentacion de dos casos.Introduccion. El sindrome del condilo occipital consiste en la presencia de cefalea occipital unilateral que empeora con los movimientos cefalicos y se acompaña de paralisis del XII par ipsilateral. La infiltracion de la base del craneo por metastasis oseas se encuentra entre sus etiologias, especialmente las que afectan por infiltracion al nervio hipogloso en su paso a traves del canal oseo. Casos clinicos. Se presentan dos casos clinicos de sindrome del condilo occipital secundario a un hepatocarcinoma metastasico. El primero, un varon de 52 años con cirrosis hepatica secundaria a hepatopatia por virus de la hepatitis C, con sindrome del condilo occipital como sintoma inicial en un hepatocarcinoma diseminado; y el segundo, un varon de 56 años, tras recidiva de un hepatocarcinoma despues de un trasplante hepatico, a pesar de no cumplir los criterios de Milan. Conclusion. El sindrome del condilo occipital es un sintoma de alarma y requiere realizar un estudio completo mediante pruebas de imagen, puesto que puede ser la primera manifestacion de un hepatocarcinoma oculto.

[How did encephalitis lethargica affect Spain? An analysis of the cases reported between 1918 and 1936]. / Cómo fue la encefalitis letárgica en España? Análisis de los casos publicados entre 1918 y 1936.

AIM: Encephalitis lethargica spread as a pandemic over the period 1918-1921. Clinically, it displayed an important degree of polymorphism and the clinical presentation varied from one outbreak to the next and from one region to another. Few studies have been carried out on the encephalitis lethargica epidemic in Spain. To determine the characteristics of its clinical and developmental features, we reviewed the cases reported in the Spanish medical literature over the period 1918-1936. DEVELOPMENT: A total of 120 cases were analysed. Most of them (75%) occurred during the winter of 1919-1920. The mean age was 27 years (range: 0-59 years). Most of them presented feverish syndromes (82%). The most frequent neurological symptoms were disorders affecting the cranial nerves, especially the oculomotor nerves, sleep rhythm disorders, altered mental or conscious status, pupillary abnormalities and movement disorders. Important variations were observed in the clinical presentation and in the developmental course. Although most cases did not present pure clinical forms, the predominant forms were somnolent-ophthalmoplegic (46%) and hyperkinetic (17%), which were associated with delusions with chorea or myoclonias. The most uncommon were amyostatic forms (Parkinsonian, 4%). The mortality rate was 23%. Most of the survivors (69%) were cured in the acute phase with no significant sequelae. CONCLUSIONS: The maximum incidence of encephalitis lethargica in Spain was registered during the winter of 1919-1920. It presented an important degree of clinical polymorphism, with predominance of an association between lethargy and ophthalmoplegia, and was linked to a high mortality rate.

[Post-encephalitic syndromes in the Spanish medical literature]. / Síndromes postencefalíticos en la literatura médica española.

AIM: A large number of patients with encephalitis lethargica developed different post-encephalitic syndromes (PES), which have an important medical and social impact. We studied the clinical and historical aspects of PES in Spain by reviewing the medical literature published in this country between 1918 and 1936. DEVELOPMENT: There are no statistical data concerning PES in Spain, although Spanish physicians drew attention to their high rate of prevalence and their repercussions on community health. Most of the 140 patients that were reviewed (74%) presented predominant Parkinsonism, but some features of Parkinsonism were observed in nearly all cases. Other movement disorders (focal dystonias, chorea, myoclonus, oculogyric crises, abnormalities affecting breathing rate) were described, as well as sleep, endocrine and vegetative disorders. Psychiatric disorders were often reported, the most frequent being bradyphrenia associated to Parkinsonism, but a hypomanic picture with impulsive behaviour was very characteristic among young people. PES was diagnosed on average two years after the episode of acute encephalitis lethargica, although it often appeared immediately afterwards. Many studies discuss the contribution made by PES to further our knowledge of the pathophysiology of extrapyramidal diseases and about the involvement of the basal ganglia in psychiatric and behavioural disorders. CONCLUSIONS: Despite the absence of statistical data, Spanish authors highlighted the important repercussions the PES had on community health, as well as the role they played in extending our knowledge of the pathophysiology of the basal ganglia. Cases of Parkinsonism were predominant, although all kinds of post-encephalitic manifestations were reported.

[Tarantism in Spain in the eighteen century: latrodectism and suggestion]. / El tarantismo en España en el siglo XVIII: latrodectismo y sugestion.

INTRODUCTION: Tarantism is the disease caused by the bite of the tarantula, in which the music tarantella triggers an involuntary dance. It is known in Italy since the sixteenth century. AIM: To analyze the tarantism reported in Spain at the end of the eighteenth century, with special attention to its neurological aspects, and to propose its medical and psychopathological explanation. DEVELOPMENT: An epidemic of people affected by the tarantula bite occurred in Spain in 1782. Spanish doctors described appropriately the clinical effects, identical to those produced by the bite of the spider black widow (Latrodectus tredecimguttatus), which was at that time identified as a tarantula. The cases reported by Francisco Xavier Cid cured with the involuntary dance triggered by the tarantella, as was described in Italy since the sixteenth century. Our interpretation is that this curative effect of dance in Spain was induced by suggestion. In Spanish patients there were no behavioral disturbances, periodic recurrences or collective involvement as those reported by Italian authors, which suggest an hysterical phenomenon, probably a continuation of the dancing mania of the Middle Age. CONCLUSIONS: Tarantism reported in Spain in the eighteenth century includes two different phenomena: the systemic symptoms produced by the tarantula bite, which is actually latrodectism, and the curative effect of the tarantella, explained by suggestion. The psychiatric disturbances, with a hysterical nature, falsely associated to the tarantula bite, observed in Italy, were not present among the Spanish cases of tarantism in the eighteenth century.

TITLE: El tarantismo en España en el siglo XVIII: latrodectismo y sugestion.Introduccion. El tarantismo es la enfermedad producida por la picadura de la tarantula, en la que la musica de la tarantela desencadena un baile involuntario. Se conoce en Italia desde el siglo XVI. Objetivo. Analizar el tarantismo descrito en España a finales del siglo XVIII, atendiendo especialmente a sus aspectos neurologicos, y proponer su explicacion medica y psicopatologica. Desarrollo. En 1782 hubo una epidemia de afectados por picadura de tarantula en España. Medicos españoles describieron correctamente los efectos clinicos, identicos a los provocados por la picadura de la araña viuda negra (Latrodectus tredecimguttatus), identificada en la epoca como tarantula. Los casos descritos por Francisco Xavier Cid curaban con el baile involuntario provocado por la tarantela, como se describia en Italia desde el siglo XVI. Interpretamos el efecto curativo de este baile en España como un fenomeno de sugestion. En los pacientes españoles no se producian los trastornos del comportamiento, las recidivas periodicas ni la afectacion colectiva descritos por autores italianos, y que sugieren un fenomeno histerico, probablemente continuacion de la mania danzante de la Edad Media. Conclusiones. El tarantismo descrito en España en el siglo XVIII incluye dos fenomenos distintos: los sintomas sistemicos producidos de la mordedura de la tarantula, que es en realidad un latrodectismo, y el efecto curativo de la tarantela, lo cual se explica por un fenomeno de sugestion. Los trastornos psiquicos falsamente asociados a la picadura de la tarantula observados en Italia, de origen histerico, no estuvieron presentes en los casos españoles de tarantismo del siglo XVIII.

Sacral myeloradiculitis complicating genital herpes in a HIV-infected patient.

Myeloradiculitis is a rare neurological complication of herpes simplex type 2 (HSV-2) infection, frequently associated with a fatal outcome. Among patients with HIV infection, HSV-2 myeloradiculitis has occasionally been reported, always associated with advanced immunosuppression and AIDS. We report a patient with HIV infection but no history of previous opportunistic infections, who developed sacral myeloradiculitis immediately after an episode of genital herpes. Magnetic resonance imaging with gadolinium showed necrotizing myelitis in the conus medullaris and enhancement of sacral roots. CD4 lymphocyte count was 530/mm3. Other possible causes of myeloradiculitis in HIV-infected patients were appropriately excluded. Acyclovir therapy resulted in partial clinical improvement. This report shows that myeloradiculitis as a complication of genital herpes may occur in the early stages of HIV infection and may have a favourable outcome with antiviral treatment.