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.

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.

[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.

[Central pontine and extrapontine myelinolysis: clinical case, brain magnetic resonance and evolution in 13 patients]. / Mielinolisis central pontina y extrapontina: cuadro clínico, resonancia magnética cerebral y evolución en 13 pacientes.

INTRODUCTION: Central pontine myelinolysis (CPM) is a disease characterized by the destruction of the myelin in the brainstem, generally associated with alcoholism, rapid correction of hyponatremia and other electrolytic alterations. The clinical symptoms, etiopathogenic factors, neuroimaging and evolution of the series of patients diagnosed of central pontine/extrapontine myelinolysis (CPEM) are described. METHODS: Review of all the clinical histories with diagnoses of CPM made in our hospital since 1989. All the cases were reviewed, ruling out those having a magnetic resonance or clinical picture not clearly consistent with the diagnosis. Age, symptoms, comorbidity, associated metabolite alterations and clinical evolution were analyzed. RESULTS: 13 cases whose ages ranged from 28 to 81 years were identified. Hyponatremia was identified during the clinical course in six patients, with neurological worsening associated to its correction in 3 of them. No sodium disorders were identified in 7 patients. Seven of the patients had associated alcoholism. Hyperintense lesions were found in all the cases in T2 sequences and FLAIR in the brainstem consistent with the typical pattern of the osmotic demyelinization syndrome. The severity of the clinical picture identified varied from a symptomatic patient to coma in 9 cases. In regards to the clinical course, four patients completely recovered, eight had residual symptoms with different severity and one patient died. CONCLUSIONS: The series is representative of the clinical and etiopathogenic spectrum of the osmotic demyelinization syndrome. Most of the clinically symptomatic patients improve if the secondary complications are controlled.

[Tethered cord syndrome in the adult]. / Síndrome de médula anclada en el adulto.

INTRODUCTION: The tethered cord syndrome (TCS) is a congenital malformation with a pathologic fixation of the spinal cord in the spinal canal. It presents clinically as musculoskeletal, cutaneous, urological and neurological manifestations. The diagnosis is based on the clinical manifestations and on the MRI (Magnetic Resonance Imaging) of the lumbar spine. It is usually diagnosed in childhood, but the symptoms can appear in adult life. METHOD: We reviewed all the cases of TCS in the adult diagnosed in our hospital between 1998 and 2005. The following parameters were evaluated: mean age at onset, initial symptoms, signs, MRI findings and outcome. RESULTS: Four 22 to 72 year old patients were diagnosed. The age at onset varied from 16 to 52 years old and the diagnosis took between 2 and 20 years to be established. The most frequent initial symptoms were the muscular atrophy and the motor weakness in the lower extremities. Two patients exhibited cutaneous stigmata (one had hypertrichosis and the other one a lipoma in the sacrum area) and one a partial agenesis of the sacrum. The most frequent MRI finding was a low lying cord with a lipoma in the sacrum area. In three patients the cord was detethered surgically, but only two of them improved. CONCLUSIONS: The TCS is an uncommon disease in adult, which is usually diagnosed very late in the adult. Because of its insidious and non specific symptomatology, and of its potential surgical treatment, it should be considered in the differential diagnosis of medullar syndromes and polyneuropathies.

[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.

[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.

[Thrombolytic treatment in acute ischemic stroke in a center without previous experience. Development of internal organization and first results]. / Tratamiento trombolítico del ictus isquémico agudo en un centro sin experiencia previa. Desarrollo de la organización interna y primeros resultados.

BACKGROUND AND OBJECTIVE: Treatment of acute ischemic stroke within three hours with intravenous tissue-type plasminogen activator (t-PA) has been recently approved by the European Drug Agency. We present the development of an internal organization system that has permitted thrombolytic treatment in our center without previous experience as well as the results of the first year. PATIENTS AND METHOD: Development of the thrombolysis educational program for the staff informed, of the internal organization system, and combined care protocols among the participating services. Prospective registry of patients treated with t-PA within the period 1/2004-2/2006. We collected demographic data, stroke assessment scales score (NIHSS), time to treatment, seven day and three months mortality, symptomatic hemorrhagic transformation, systemic bleedings, functional independency at three months, early significant improvement and significant deterioration. RESULTS: Fifty-three patients were treated. Mean age: 65 +/- 13 years; 56% women. Mean NIHSS pre-treatment: 14 +/- 4.7. Mean time to hospital arrival: 62 +/- 40 minutes; door-to-treatment: 68 +/- 22 minutes, and mean time from stroke onset to treatment: 130 +/- 31 minutes. Symptomatic hemorrhagic transformation: 5.8%. Systemic bleeding: 3.8%. Seven day mortality: 5.6%; three months mortality: 15.1%. Early significant improvement: 51%. Significant neurological deterioration: 7.5%. Functional independency at three months: 51%. CONCLUSIONS: Treatment of acute ischemic stroke within three hours with intravenous t-PA is safe and is associated with a favourable outcome when it is applied by neurologists specifically trained in acute stroke management.

[The Martín Larios affair and the beginnings of neurology in Spain. Charcot refuted by Escuder, Vera and Simarro]. / El asunto Martín Larios y los inicios de la neurología en España: Charcot refutado por Escuder, Vera y Simarro.

Jean Martin Charcot travelled to Spain in December 1887 in the company of Alfred Hardy for the medical examination of Martin Larios y Larios, a member of the Spanish parliament. Martín Larios had shown behavioral disturbances and had married secretly for the second time against the advice of his family, one of the richest and more dominating families in Spain during the 19th century. In their report Charcot and Hardy gave a diagnosis of mental insanity probably due to general paresis, as they had noted memory deficits and delusion of grandeur. With this and other medical reports, the family tried to obtain the legal incapacity of Martín Larios. Initially the judgements favoured the incapacity, but Martín Larios and his wife appealed with the support of the Spanish doctors José María Escuder, Jaime Vera and Luis Simarro. They demonstrated, in an exhaustive and clinically rigorous report, the normality of the mental status of Martín Larios, and refuted the diagnosis given by Charcot and Hardy. This report is one of the first examples of the clinical evaluation of a neurologic patient in Spain and shows the high clinical standards achieved by the precursors of the neurological school of Madrid. The great influence of Charcot's own school over Spanish neurology in its beginnings stands out in this report. Charcot and Hardy wrote a second report in reply to Escuder, Vera and Simarro. After a complex lawsuit, the opinion of the Spanish doctors finally prevailed against the legal incapacity of Martín Larios.

Cajal's views on the Nobel Prize for physiology and medicine (October 1904).

In this report we present and discuss an unpublished letter written by Santiago Ramon y Cajal in October 1904 in relation to his possible nomination for the Nobel Prize for Physiology and Medicine. This letter shows that Cajal was aware of his previous nominations for the Prize. He was convinced that these nominations had not been successful because neither anatomy nor histology were among the sciences included in the Nobel Statutes' definition of Physiology or Medicine. He gives a list of the merits he thought might be used for a new nomination, which included only works concluded during the previous five years.