Ischaemic stroke and SARS-CoV-2 infection: A causal or incidental association? / Ictus isquémico e infección por SARS-CoV-2, ¿asociación casual o causal?

INTRODUCTION: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. METHODS: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. RESULTS: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. CONCLUSIONS: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed.

An initial experience with intraoperative O-Arm for deep brain stimulation surgery: can it replace post-operative MRI?

Deep brain stimulation (DBS) is used to treat movement disorders, severe psychiatric disorders, and neuropathic pain, among other diseases. Advanced neuroimaging techniques allow direct or indirect localization of the target site, which is verified in many centers by the intraoperative recording of unitary neuronal activity. Intraoperative image acquisition technology (e.g., O-Arm) is increasingly used for accurate electrode positioning throughout the surgery. The aim of our study is to analyze the initial experience of our team in the utilization of O-Arm for planning DBS and monitoring its precision and accuracy throughout the procedure. The study included 13 patients with movement disorders. All underwent DBS with the intraoperative O-arm image acquisition system (iCT) and Medtronic StealthStation S7 cranial planning system, placing a total of 25 electrodes. For each patient, we calculated the difference between real and theoretic x, y, z coordinates, using the paired Student's t test to evaluate absolute and directional differences and the one-sample Student's t test to analyze differences in Euclidean distances. No statistically significant differences were found in absolute, directional, or Euclidean distances between intended and actual x, y, and z coordinates, based on iCT scan. Our experience confirms that utilization of the O-Arm system in DBS provides accurate and precise verification of electrode placements throughout the procedure. Recent studies found no significant differences between iCT and postoperative MRI, the current gold standard. Further prospective studies are warranted to test the elimination of postoperative MRI when this system is used.

Stroke-related mortality in a tertiary care hospital in Andalusia: Analysis and reflections. / Mortalidad asociada al ictus en un hospital andaluz de tercer nivel. Análisis y reflexiones.

OBJECTIVES: Stroke is a very common cause of death, especially in southern Spain. The present study analyses in-hospital mortality associated with stroke in an Andalusian tertiary care hospital. METHODS: We gathered the files of all patients who had died at Hospital Universitario Virgen de las Nieves in Granada in 2013 and whose death certificates indicated stroke as the cause of death. We also gathered stroke patients discharge data and compared them to that of patients with acute coronary syndrome (ACS). RESULTS: A total of 825 patients had a diagnosis of stroke (96 deaths, 11.6%); of these, 562 had ischaemic stroke (44 deaths, 7.8%) and 263 haemorrhagic stroke (52 deaths, 19.7%). Patients with haemorrhagic stroke therefore showed greater mortality rate (OR=2.9). Patients in this group died after a shorter time in hospital (median, 4 vs 7 days; mean, 6 days). However, patients with ischaemic stroke were older and presented with more comorbidities. On the other hand, 617 patients had a diagnosis of ACS (36 deaths, 5.8%). The mortality odds ratio (MOR) was 2.1 (stroke/SCA). Around 23% of the patients who died from stroke were taking anticoagulants. 60% of the deceased patients with ischaemic stroke and 20% of those with haemorrhagic stroke had atrial fibrillation (AF); 35% of the patients with ischaemic stroke and AF were taking anticoagulants. CONCLUSIONS: Stroke is associated with higher admission and in-hospital mortality rates than SCA. Likewise, patients with haemorrhagic stroke showed higher mortality rates than those with ischaemic stroke. Patients with fatal stroke usually had a history of long-term treatment with anticoagulants; 2 thirds of the patients with fatal ischaemic stroke and atrial fibrillation were not receiving anticoagulants. According to our results, optimising prevention in patients with AF may have a positive impact on stroke-related in-hospital mortality.

Abnormal thermography in Parkinson's disease.

BACKGROUND: An autonomic denervation and abnormal vasomotor reflex in the skin have been described in Parkinson's disease (PD) and might be evaluable using thermography with cold stress test. METHODS: A cross-sectional pilot study was undertaken in 35 adults: 15 patients with PD and abnormal [(123)I]-metaiodobenzylguanidine cardiac scintigraphy and 20 healthy controls. Baseline thermography of both hands was obtained before immersing one in cold water (3 ± 1 °C) for 2 min. Continuous thermography was performed in: non-immersed hand (right or with lesser motor involvement) during immersion of the contralateral hand and for 6 min afterward; and contralateral immersed hand for 6 min post-immersion. The region of interest was the dorsal skin of the third finger, distal phalanx. RESULTS: PD patients showed a lower mean baseline hand temperature (p = 0.037) and greater thermal difference between dorsum of wrist and third finger (p = 0.036) and between hands (p = 0.0001) versus controls, regardless of the motor laterality. Both tests evidenced an adequate capacity to differentiate between groups: in the non-immersed hand, the PD patients did not show the normal cooling pattern or final thermal overshoot observed in controls (F = 5.29; p = 0.001), and there was an AUC of 0.897 (95%CI 0.796-0.998) for this cooling; in the immersed hand, thermal recovery at 6 min post-immersion was lesser in patients (29 ± 17% vs. 55 ± 28%, p = 0.002), with an AUC of 0.810 (95%CI 0.662-0.958). CONCLUSIONS: PD patients reveal abnormal skin thermal responses in thermography with cold stress test, suggesting cutaneous autonomic dysfunction. This simple technique may be useful to evaluate autonomic dysfunction in PD.

Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in Parkinson's disease.

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS - NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS - Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery.

[Calamities in movement disorders]. / Catástrofes en trastornos del movimiento.

The field of movement disorders largely covers subacute or chronic diseases that are usually treated in outpatient clinics. However, the much less frequent acute disorders require urgent recognition and treatment. The present article reviews the entities that frequently require neurointensive management and whose development can prove "calamitous". These include neuroleptic malignant syndrome and related conditions, status dystonicus, and hemiballism.

Efficacy and safety of pallidal stimulation in primary dystonia: results of the Spanish multicentric study.

BACKGROUND: Dystonia is a complex clinical syndrome originated by a wide range of aetiologies. The diagnosis of dystonia is made after the evaluation of aetiological, phenomenological and genetic factors. Medications, except in patients with dopa-responsive dystonia, are of limited efficacy. Botulinum toxin injections are not applicable to patients with generalised dystonia, since many muscular groups contribute to disability. Clinical studies in children and adults with primary generalised dystonia (PGD) have reported beneficial effects of bilateral GPi deep brain stimulation (DBS) in both motor symptoms and disability produced by dystonia as well as a favourable impact of DBS in the health-related quality of life (HRQoL). Some clinical aspects of GPi stimulation in primary dystonia still remain controversial such as the influence of disease duration or age at onset in determining the postoperative clinical outcome. RESULTS: The authors report the results of a multicentric study designed to assess the tolerability and clinical effects of bilateral pallidal DBS on motor impairment, functional disability, quality of life, pain and mood in patients with medically refractory primary generalised or segmental dystonia.

[Diagnostic value of cardiac 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy in Lewy body disorders]. / Valor diagnóstico de la gammagrafía cardíaca con 123I-metaiodobenzilguanidina en las enfermedades con cuerpos de Lewy.

INTRODUCTION: Lewy body disorders such as Parkinson's disease (PD) and Lewy body dementia (LBD) are associated with cardiac sympathetic denervation, which can be visualized on 123I-MIBG scintigraphy. Our objectives were to study the diagnostic value of this technique in Lewy body disorders and its relationship with PD clinical variables. PATIENTS AND METHODS: We studied 90 patients: 51 with PD, 19 with LBD, 9 with multiple system atrophy (MSA) and 11 controls. Scintigraphy images were qualitatively evaluated and early and delayed heart-to-mediastinum ratios (HMR) were calculated. The main confounding factors (ischemic heart disease, diabetes, hypertension and drugs) were controlled by multivariate linear regression analysis. We investigated correlations between scintigraphy variables and PD variables. RESULTS: The delayed HMR, which showed better discriminative ability was 2.03 +/- 0.32 in controls, 1.37 +/- 0.30 in PD (p<0.001 vs controls), 1.47+/-0.45 in LBD (p=0.001 vs controls) and 1.69+/-0.28 in MSA (p=0.02 vs controls; p=0.004 vs PD). This ratio was influenced by PD/LBD diagnosis (beta= -0.638; p<0.001) and to a lesser degree, by ischemic heart disease (beta= -0.244; p=0.028). Optimal cut-off value between PD/LBD and controls was 1.71 (83% sensitivity and 82% specificity). Within the PD group, those with a family history of PD/LB showed higher delayed HMR values (1.65+/-0.34 vs 1.30+/-0.24 without history; p<0.001) and proportion with normal scintigraphy (56% vs 5%; p=0.001). CONCLUSIONS: Cardiac 123I-MIBG scintigraphy is useful in the diagnosis of Lewy body disorders, although its value in PD is conditioned by having a family history of PD.

Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders?: a cohort study.

OBJECTIVE: To determine the prevalence of alpha-synuclein (AS) aggregates in abdominopelvic autonomic plexuses in the general population and to evaluate the relationship between this finding and the subsequent development of neurologic dysfunction. METHODS: First, surgical specimens from 100 patients (ages 44 to 84) undergoing a wide resection of an abdominopelvic organ were examined by anti-AS immunostaining. Second, 16 patients (6 AS+ and 10 randomly selected AS-) participated in yearly double-blinded neurologic assessments. RESULTS: AS aggregates were found in autonomic plexuses in 9% of the whole sample (95% CI 3.4 to 14.6%) but were more common in vesicoprostatic (26%) than in digestive tract (4%) specimens. At 16 months after the biopsy, no prevalent cases of Parkinson disease, dementia, or autonomic failure were diagnosed among participants. One AS+ patient had previously been diagnosed with REM sleep behavior disorder. Seven of 10 control subjects but none of the 6 AS+ patients had a diagnosis of hypertension (p = 0.01). During phase IV of Valsalva maneuver, AS+ group exhibited a longer blood pressure recovery time (p = 0.03), with one patient showing absence of blood pressure overshoot. Cardiac [(123)I]metaiodobenzylguanidine uptake was reduced in the AS+ group (p = 0.03). Striatal [(123)I]ioflupane uptake was abnormally low in only one AS+ patient. At 30 months after the biopsy, lower cardiac and striatal uptake values tended to correlate with higher Unified Parkinson's Disease Rating Scale III scores (p = 0.07). CONCLUSION: The common presence of alpha-synuclein aggregates in peripheral autonomic neurons may represent an early presymptomatic phase in the development of Lewy body disorders.

[Cell therapy and other neuroregenerative strategies in Parkinson's disease (II)]. / Terapia celular y otras estrategias neurorregenerativas en la enfermedad de Parkinson (II).

OBJECTIVE: To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease (PD). A previous first part focused on the results of adrenal medulla and human fetal mesencephalic transplants, and this second part addresses transplants of other cell types, administration of trophic factors, and gene therapy. DEVELOPMENT: As an alternative to human fetal mesencephalic neurons, other donor cells types (porcine mesencephalic neurons, retinal pigment epithelial cells) with similar 'dopaminergic' action mechanism have been tried, although with heterogeneous results. Transplantation of carotid body cell aggregates may be a promising therapy because of its neurotrophic action mechanism. The perspectives of cell therapies based on genetically modified cells and precursor cells of different origin are also reviewed. Among other neuroregenerative approaches, the clinical outcomes of direct administration of neurotrophic factors and the perspectives for in vivo gene therapy are also addressed. CONCLUSIONS: The objective of neuroregenerative therapy for PD should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells), and in vivo gene therapy.

[Cell therapy and other neuroregenerative strategies in Parkinson's disease (I)]. / Terapia celular y otras estrategias neurorregenerativas en la enfermedad de Parkinson (I).

OBJECTIVE: To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease. This first part focuses on the results of adrenal medulla and human fetal mesencephalic transplants, and a second part will address transplants of other cell types, administration of trophic factors, and gene therapy. DEVELOPMENT: Adrenal medulla transplants were abandoned because of their inconsistent results and high morbidity. Although fetal mesencephalic transplantation can produce long-term restoration of striatal dopamine deficiency, this neurochemical effect is clinically inadequate in presence of progressive neuronal loss. Other strategies with similar 'dopaminergic' action mechanism are not a therapeutic option in this setting. CONCLUSIONS: The objective of neuroregenerative therapy for Parkinson's disease should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells, including stem cells), and in vivo gene therapy.

Different patterns of medication change after subthalamic or pallidal stimulation for Parkinson's disease: target related effect or selection bias?

BACKGROUND: Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is favoured over bilateral globus pallidus internus (Gpi) DBS for symptomatic treatment of advanced Parkinson's disease (PD) due to the possibility of reducing medication, despite lack of definitive comparative evidence. OBJECTIVE: To analyse outcomes after one year of bilateral Gpi or STN DBS, with consideration of influence of selection bias on the pattern of postsurgical medication change. METHODS: The first patients to undergo bilateral Gpi (n = 10) or STN (n = 10) DBS at our centre were studied. They were assessed presurgically and one year after surgery (CAPIT protocol). RESULTS: Before surgery the Gpi DBS group had more dyskinesias and received lower doses of medication. At one year, mean reduction in UPDRS off medication score was 35% and 39% in the Gpi and STN groups, respectively (non-significant difference). Dyskinesias reduced in proportion to presurgical severity. The levodopa equivalent dose was significantly reduced only in the STN group (24%). This study high-lights the absence of significant differences between the groups in clinical scales and medication dose at one year. In the multivariate analysis of predictive factors for off-state motor improvement, the presurgical levodopa equivalent dose showed a direct relation in the STN and an inverse relation in the Gpi group. CONCLUSION: Differences in the patterns of medication change after Gpi and STN DBS may be partly due to a patient selection bias. Both procedures may be equally useful for different subgroups of patients with advanced PD, Gpi DBS especially for patients with lower threshold for dyskinesia.

[Clinical utility of deep brain stimulation in an advanced Parkinson's disease]. / Utilidad clínica de la estimulación cerebral profunda en la enfermedad de Parkinson avanzada.

INTRODUCTION: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) have demonstrated efficacy in advanced Parkinson's disease (PD). We aimed to assess the clinical utility of these procedures in terms of the quality of life, and to determine the pre and postsurgical characteristics related to the outcome. METHOD: A prospective study was conducted on a cohort of 20 patients with advanced PD who underwent bilateral DBS: 14 in STN and 6 in GPi. They were assessed according to the CAPSIT-PD protocol before and after surgery, with a mean follow-up of 9 and 11 months, respectively. The main outcome variables were change in the UPDRS III score in off efficacy and the PDQ-39 quality of life questionnaire score (clinical utility). RESULTS: The STN group improved their UPDRS III in off by a mean of 35% (p = 0.001) and their PDQ-39 by 21% (p = 0.026). The GPi group improved their UPDRS III in off by 21% (p = 0.028) and their PDQ-39 by 37% (p = 0.116). The presurgical levodopa-equivalent dose was a positive predictor of the efficacy and clinical utility of STN DBS and a negative predictor of the efficacy of GPi DBS. In both groups, the clinical utility was determined by improvement in functional disability in off scales. CONCLUSIONS: Bilateral DBS demonstrated middle-term efficacy and clinical utility in the treatment of advanced PD. The presurgical levodopa-equivalent dose was a predictor of the efficacy and clinical utility of DBS.

[Callosotomy in the treatment of drug-resistant epilepsy]. / La callosotomía en el tratamiento de la epilepsia farmacorresistente.

At the present time corpus callosotomy is a valuable option in the management of some patients with drug-resistant epilepsy who are not candidates for resective procedures. The records of six patients who underwent callosotomy at 'Hospital Virgen de las Nieves' (Granada, Spain) in the past four years were retrospectively analyzed. The patients all had intractable primary or secondarily generalized seizures, were severely handicapped by its frequency and nature (especially with drop attacks and multiple injuries) and were not suitable for other surgical procedure. The results of surgery (five anterior callosotomies and one subtotal section) are described after an average follow-up period of 2.5 years. Overall, four patients achieved significant improvement (at least 50% reduction in seizure frequency, severity, or both, affecting quality of life), with a marked reduction (> 75%) in two of them. There was no clinical deterioration, significant surgical complication nor relevant additional long-term neuro-psychological deficit in any case. Previous studies have been reviewed mainly to find those prognostic factors associated with a better seizure outcome or with the occurrence of complications. The best results are obtained in those patients with drop attacks (including atonic seizures) as the most frequent and disabling seizure type. According to the type of epilepsy, patients with localization-related epilepsy (especially when symptomatic of a focal brain damage) and those with the Lennox-Gastaut syndrome are the most likely to benefit from the procedure. It is suggested that, in the first place, a two-thirds anterior callosotomy should be performed particularly with atonic seizure are the most frequent seizure type. We may proceed with completion of callosal division as a second stage in those patients in whom a significant improvement has not been observed. In severely retarded patients with multiple seizure types, one-stage complete section may be performed. The procedure is relatively safe, with a low incidence of morbidity and clinically significant long-term neuro-psychological deficits. Further larger clinical studies are necessary to elucidate many aspects which are still unresolved. More uniformity would be desirable in the evaluation of patients, surgical technique, follow-up and presentation of results.

[Non-giant cell temporal arteritis as a manifestation of Churg-Strauss syndrome. Presentation of a case and review of literature]. / Arteritis no de células gigantes de la temporal como manifestación clínica del síndrome de Churg-Strauss. Presentación de un caso y revisión de la literatura.

Most cases of temporal arteritis are of the giant cell variety, with cases involving other histologic patterns occurring rarely. There are only 4 descriptions in the literature of non giant cell temporal arteritis as a manifestation of Churg-Strauss syndrome. We report the case of a 74-year-old man with a history of bronchial asthma who presented with systemic symptoms and right temporal cephalea with diplopia, diffuse muscle pain and transient skin lesions on the extremities. The right temporal artery was enlarged and painful but pulsatile. Tests showed a high erythrocyte sedimentation rate and leukocytosis with relative and absolute eosinophilia. Biopsy of the temporal artery revealed polymorphic inflammatory infiltration throughout the vas, with numerous eosinophils and non giant cells, confirming a diagnosis of Churg-Strauss syndrome with extension to the temporal artery. Temporal arteritis should be considered a syndrome with variable substrate pathology; the possibility that it is a rare manifestation of systemic necrotizing vasculitis should not be ruled out.

[Complete third nerve paralysis as clinical presentation of multiple sclerosis]. / Parálisis completa del tercer par como forma de presentación de esclerosis múltiple.

An acute attack of cephalea and third nerve palsy with pupillary involvement may be caused by a variety of entities, but aneurysm of the posterior communicating artery must certainly be ruled out. We describe a 22 year old patient in whom this clinical profile was an unusual first sign of multiple sclerosis.

[Clinical iconographic dissociation in a case of monophasic demyelinating disease]. / Disociación clinicoiconográfica en un caso de enfermedad desmielinizante monofásica.

We report a patient with monophasic inflammatory demyelinizing disease whose initial symptoms and imaging studies led to the undertaking of a cerebral biopsy for suspicion of an expansive process. The evolution of the both the CT and MR imaging studies with contrast and overall the surprising size of the lesions in MR when the patient was clinically asymptomatic support the hypothesis of residual dysfunction in the hemato-encephalic barrier as a cause of the persistence of MR images. This explanation appears more acceptable than its attribution to a gliosis secondary to previous inflammation.