Epidemiology, pathophysiology, and classification of the neurological symptoms of post-COVID-19 syndrome.

Introduction: Post-COVID-19 syndrome is a series of chronic signs and symptoms that may appear after SARS-CoV-2 infection, including fatigue, dyspnoea, chest pain, palpitations, anxiety, depression, and joint and muscle pain. The purpose of this study was to review the controversies on post-COVID-19 syndrome, the frequency of neurological symptoms, and the potential pathophysiological mechanisms. Methods: We present a narrative review of studies published in PubMed since the beginning of the pandemic (January 2020-July 2021). Results: Patients with history of COVID-19 have been found to present persistent neurological symptoms, including cognitive complaints, memory and concentration problems, headache, anosmia, ageusia, vertigo, and insomnia. Post-COVID-19 syndrome is a heterogeneous disease that lacks a universally accepted definition, which may explain the great variability in the estimated prevalence (2.3%-85%) and symptom duration. The criteria differentiating post-COVID-19 syndrome from chronic fatigue syndrome or critical illness syndrome are ambiguous. Risk factors include older age, female sex, certain comorbidities, and greater number of symptoms in the acute phase. The pathophysiology of the syndrome is largely unknown, although it is probably multifactorial, including immunological mechanisms, neural network dysfunction, neurotransmitter alterations, persistent viral damage, and functional impairment. Conclusions: Post-COVID-19 syndrome may present after mild or even asymptomatic SARS-CoV-2 infection, causing limitations in activities of daily living and in quality of life. Further research will clarify the origin and most appropriate management of these neurological alterations.

Introducción: El término "síndrome post-COVID" se emplea para describir una serie de signos y síntomas crónicos que pueden surgir tras la infección por el virus SARS-CoV-2, como fatiga, disnea, dolor torácico, palpitaciones, ansiedad, depresión, dolores articulares y musculares entre otros. El objetivo es revisar las controversias asociadas al síndrome post-COVID-19, la frecuencia de los síntomas neurológicos y su posible fisiopatología. Métodos: Revisión narrativa crítica de los estudios publicados desde el inicio de la pandemia en pubmed (enero 2020 a julio 2021). Resultados: Síntomas neurológicos persistentes (quejas cognitivas, problemas de memoria y concentración; cefalea, anosmia, ageusia, vértigo, insomnio, etc) se han descrito en personas que padecieron COVID-19. El síndrome post-COVID-19 no es una entidad homogénea y no tiene una definición universalmente aceptada, lo que explica la variación en las estimaciones sobre prevalencia (2,3%­85%) y duración de los síntomas. Los criterios que lo distinguen del síndrome de fatiga crónica o el síndrome del paciente crítico son ambiguos. Los factores de riesgo incluyen edad, sexo (mujer), comorbidades, y número de síntomas en la fase aguda. La fisiopatología es en gran medida desconocida, pero probablemente multifactorial, incluyendo mecanismos inmunológicos, disfunción de redes neuronales y alteración de neurotransmisores, daño viral persistente, y cuadros de origen funcional, entre otros. Conclusiones: Los síntomas post-COVID-19 pueden surgir tras padecer una infección leve o incluso asintomática, y causa limitaciones en las actividades de la vida diaria y calidad de vida. El progreso en la investigación nos ayudará a aclarar el origen y manejo de estas complejas alteraciones neurológicas.

Bilateral facial nerve palsy associated with COVID-19 and Epstein-Barr virus co-infection.

COVID-19 can occasionally be associated with cranial nerve involvement, but facial palsy, particularly if bilateral, is exceptional. We here report a patient who presented with severe bilateral facial palsy and evidence of SARS-CoV-2 infection preceded by upper respiratory symptoms. He also had serological evidence of coinfection with Epstein-Barr virus, which could have also played a role in his neurological manifestations. PCR in the cerebrospinal fluid was negative for both EBV and SARS-CoV-2, which suggests an indirect, immune-mediated mechanism rather than direct, viral-induced damage. The patient was treated with prednisone 60 mg/24h with a tapering schedule and had a favorable outcome, with an almost complete recovery in 3 weeks. SARS-CoV-2 adds to the list of infectious agents causative of bilateral facial palsy. Coinfection with SARS-CoV-2 is not rare and should be considered in the differential diagnosis.

[Reversible alterations in the dentate nuclei and rapid-onset cerebral atrophy due to neurotoxicity caused by lithium]. / Alteraciones reversibles en los nucleos dentados y atrofia cerebral de rapida instauracion debido a neurotoxicidad por litio.

INTRODUCTION: Treatment with lithium can cause several neurological side effects, even at therapeutic levels. CASE REPORT: We report the case of a 49-year-old woman, with bipolar disorder and depression, undergoing treatment with lithium, antidepressants and antipsychotics, who was admitted to hospital due to a clinical picture of visual hallucinations with an elevated lithaemia of 2.1 mEq/L (therapeutic range: 0.6-1.2 mEq/L). The patient developed a severe encephalopathy that required the use of assisted ventilation in the intensive care unit. Initial magnetic resonance imaging showed a reversible bilateral symmetrical hyperintensity in the dentate nuclei in T2 and T2-FLAIR sequences. Over the following months she gradually developed a pancerebellar syndrome with evidence of a marked loss of bilateral volume in the cerebellum, above all at the expense of the vermis, which was accompanied by a permanent and disabling cerebellar syndrome. CONCLUSIONS: Although treatment with lithium can cause a variety of neurological side effects, they are usually reversible. However, they occasionally give rise to permanent and disabling sequelae, as in the case of the patient reported here, with a marked and progressive cerebellar atrophy, accompanied by permanent sequelae in the form of a disabling cerebellar syndrome. The cerebellar neurotoxicity of lithium must be taken into account in the broad differential diagnosis of cerebellar ataxia in adults.

TITLE: Alteraciones reversibles en los nucleos dentados y atrofia cerebral de rapida instauracion debido a neurotoxicidad por litio.Introduccion. El tratamiento con litio puede ocasionar diversos efectos adversos neurologicos, incluso con niveles terapeuticos. Caso clinico. Mujer de 49 años, con trastorno bipolar y depresion, en tratamiento con litio, antidepresivos y antipsicoticos, que ingreso por un cuadro de alucinaciones visuales con una litemia elevada de 2,1 mEq/L (rango terapeutico: 0,6-1,2 mEq/L). Progreso a una encefalopatia grave que requirio asistencia respiratoria en la unidad de cuidados intensivos. La resonancia magnetica cerebral inicial mostro una hiperintensidad simetrica bilateral reversible en los nucleos dentados en las secuencias T2 y T2-FLAIR. A lo largo de los meses posteriores desarrollo de forma progresiva un sindrome pancerebeloso con evidencia de una marcada perdida de volumen bilateral en el cerebelo, sobre todo a expensas del vermis, que se acompaño clinicamente de un sindrome cerebeloso permanente e invalidante. Conclusiones. Aunque el tratamiento con litio ocasiona efectos adversos neurologicos variados, estos suelen ser reversibles. Puede dar lugar a secuelas permanentes e incapacitantes, como la paciente descrita, con una atrofia cerebelosa marcada y progresiva, acompañada de secuelas permanentes en forma de sindrome cerebeloso invalidante. La neurotoxicidad cerebelosa del litio debe considerarse en el amplio diagnostico diferencial que representa la ataxia cerebelosa del adulto.

[Personality factors, degree of disability and therapeutic management of patients with migraine visiting a neurology unit for the first time (Psicomig study)]. / Factores de personalidad, grado de discapacidad y abordaje terapeutico de los pacientes con migrana atendidos en primera consulta en neurologia (estudio Psicomig).

INTRODUCTION: Migraine has recently been associated to certain personality profiles and styles of coping. AIM: To explore the association between personality factors, disability and the therapeutic management of migraine. PATIENTS AND METHODS: We conducted an epidemiological, cross-sectional, multi-centre study with patients with migraine visiting a neurology unit for the first time. Socio-demographic and clinical data were collected about the patients. The NEO-FFI (Neuroticism-Extraversion-Openness Five-Factor Inventory) was used to evaluate personality factors; the degree of disability was evaluated using the Headache Impact Test (HIT-6) and the number of lost workday equivalents (LWDE) was measured. Bivariate logistic regression analyses were also performed. RESULTS: A total of 736 patients were recruited, of whom 700 were suitable for inclusion in the analysis (75.6% females; mean age: 35.5 ± 11.5 years). In all, 68.9% presented migraine without aura, 1-4 seizures/month (66.7%) and of moderate intensity (58.1%). A total of 76.1% of patients had severe disability according to the HIT-6. Of the 554 active patients, the mean number of lost workday equivalents in the previous three months was 6.8 ± 8.2. Patients showed greater emotional instability than the general population and they scored lower on extraversion, openness, agreeableness and conscientiousness. All the patients were being treated for their migraine: 47.3% by means of stepped treatment between seizures; 39.9% intra-seizures, and stratified in only 12.9%. CONCLUSIONS: This study confirms the impact of migraine in terms of disability and in terms of loss of labour output, together with its association with personality factors.

[Acute encephalitis]. / Encefalitis agudas.

Acute encephalitis can be due to many causes, although most are viral, and is a medical emergency. A significant percentage remains without a definitive diagnosis due to the large number of etiologic agents. The single most frequent cause of sporadic encephalitis around the world is herpes simplex virus type 1, although in certain locations diverse local agents should be considered such as West Nile virus or tick-borne encephalitis, among others. Patients with encephalitis require intense care measures with special emphasis on respiratory problems secondary to a depressed level of consciousness, seizures, and intracranial hypertension due to cerebral edema. Herpes encephalitis has an incidence of 4 cases per million inhabitants. Clinical presentation, together with electroencephalography, magnetic resonance imaging and cerebrospinal fluid (CSF) findings are critical to establish a diagnosis. Polymerase chain reaction (PCR) in CSF is highly sensitive and specific (> 95%), but the results can be negative during the first 3 days of the disease. The treatment of choice is currently acyclovir 10 mg/kg/8 h for 10-21 days. Whenever resistance is suspected, foscarnet is an alternative. The family of arboviruses represents another important etiologic group of encephalities. These are zoonotic diseases transmitted by mosquitoes or ticks and include alphaviruses, bunyaviruses (Toscana virus and others) and flaviviruses. The West Nile virus belongs to the latter group. There is no specific therapy and diagnosis is based on serology and PCR depending on the suspected virus.

Encefalitis agudas / Acute encephalitis

La encefalitis aguda es una emergencia médica de etiología variada, aunque en su mayoría es viral. Un porcentaje elevado queda sin un diagnóstico etiológico específico debido al gran número de agentes causales. La causa más frecuente de encefalitis esporádica en todo el mundo es el virus del herpes simple tipo 1, aunque en determinadas localizaciones es importante considerar determinados agentes locales, como el virus del Nilo Occidental o la encefalitis transmitida por garrapata, entre otros. Los pacientes con encefalitis requieren cuidados generales, con especial énfasis en los problemas respiratorios derivados del deterioro del nivel de consciencia, las crisis epilépticas y la hipertensión intracraneal secundaria al edema cerebral. La encefalitis herpética tiene una incidencia de 4 casos por millón de habitantes. La presentación clínica junto al EEG, la RM y el análisis del LCR son claves en su diagnóstico. La PCR en el LCR es altamente sensible y específica (> 95%), aunque puede ser negativa en los primeros 3 días de enfermedad. El tratamiento de elección en la actualidad es el aciclovir intravenoso, a una dosis de 10 mg/kg/8 h, durante 10-21 días. En casos de resistencia, el foscarnet es una alternativa. Los arbovirus constituyen otro importante grupo etiológico en las encefalitis. Son zoonosis transmitidas por mosquitos o garrapatas e incluyen los alfa-virus, los bunyavirus (el virus de la Toscana y otros) y los flavivirus. Entre estos últimos destaca el virus del Nilo Occidental. No hay tratamiento específico y el diagnóstico se basa en la serología o la PCR dependiendo del tipo de virus (AU)

Acute encephalitis can be due to many causes, although most are viral, and is a medical emergency. A significant percentage remains without a definitive diagnosis due to the large number of etiologic agents. The single most frequent cause of sporadic encephalitis around the world is herpes simplex virus type 1, although in certain locations diverse local agents should be considered such as West Nile virus or tick-borne encephalitis, among others. Patients with encephalitis require intense care measures with special emphasis on respiratory problems secondary to a depressed level of consciousness, seizures, and intracranial hypertension due to cerebral edema. Herpes encephalitis has an incidence of 4 cases per million inhabitants. Clinical presentation, together with electroencephalography, magnetic resonance imaging and cerebrospinal fluid (CSF) findings are critical to establish a diagnosis. Polymerase chain reaction (PCR) in CSF is highly sensitive and specific (> 95%), but the results can be negative during the first 3 days of the disease. The treatment of choice is currently acyclovir 10 mg/kg/8 h for 10-21 days. Whenever resistance is suspected, foscarnet is an alternative. The family of arboviruses represents another important etiologic group of encephalities. These are zoonotic diseases transmitted by mosquitoes or ticks and include alphaviruses, bunyaviruses (Toscana virus and others) and flaviviruses. The West Nile virus belongs to the latter group. There is no specific therapy and diagnosis is based on serology and PCR depending on the suspected virus (AU)

Response to intravenous lidocaine in a patient with SUNCT syndrome.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome represents a serious therapeutic and diagnostic challenge, since it is usually refractory to most drugs and lacks biological markers. Response to intravenous lidocaine administration has been reported in some patients while it has failed in others. We report a patient with SUNCT syndrome who showed a clear-cut and consistent response to intravenous lidocaine therapy, which proved superior to placebo in a single-blinded fashion. Intravenous lidocaine should be considered in all patients with SUNCT syndrome. Response to this therapy could represent a diagnostic tool.

[Spinal cord hemorrhage complicating diagnostic lumbar puncture]. / Complicación espinal hemorrágica secundaria a una punción lumbar diagnóstica.

INTRODUCTION: Spinal cord hematoma is a serious and feared complication of lumbar puncture. We here describe two patients who developed a spinal cord hematoma following diagnostic lumbar punctures. CASE REPORTS: CASE 1: a 22-year-old male with a syndrome of cerebrospinal fluid hypotension, with normal coagulation parameters, underwent a traumatic, diagnostic lumbar puncture followed, a few hours later, by back pain irradiated to the legs. MRI showed the presence of a subdural hematoma from the lower dorsal region to the sacral region. A conservative approach, without surgery, was decided and he showed a complete recovery. CASE 2: a 69-year-old woman underwent a diagnostic lumbar puncture for the study of recent-onset headache with tinnitus and unstable gait. Puncture was traumatic and cerebrospinal fluid was normal. A few hours later, she complained of back pain and sciatica, and examination revealed a bilateral Lassegue sign. She required urinary catheterization. MRI showed an epidural hematoma from the T10 vertebra to the sacral area. Her outcome with a conservative approach was also excellent. CONCLUSIONS: Spinal cord hematomas can occur after a traumatic lumbar puncture in people without coagulation disorders or any other predisposing factor. Although surgery has been traditionally advocated in these cases, a conservative approach is an option when symptoms are mild and a close follow-up is possible.

Impact of preventive therapy with nadolol and topiramate on the quality of life of migraine patients.

Preventive therapy is aimed at reducing migraine frequency, but should also improve the much deteriorated quality of life of the migraneur. We aimed to evaluate the impact of preventive therapy with two widely employed drugs (topiramate and nadolol) on the quality of life of migraine patients. A population of consecutive migraineurs aged > or = 16 years, with frequent migraines, was selected prospectively for evaluation at baseline and after 16 weeks of therapy with nadolol or topiramate (40 mg and 100 mg daily, respectively) by generic and specific quality of life questionnaires (SF-36 and MSQOL) and by an anxiety and depression scale (HADS). Preventive therapy resulted in a statistically significant improvement in physical domains of the SF-36, whereas mental domains remained almost unchanged. Despite this improvement, all domains remained below the population norms. The HADS revealed a moderate depressive state at baseline that did not change with therapy. The MSQOL global score also revealed statistically significant improvement. Both drugs were similarly effective, although topiramate was superior on the role physical domain compared with nadolol. Preventive therapy with nadolol and topiramate significantly improves the quality of life of migraineurs, although additional efforts are needed to place them in a nearer-to-normal situation compared with the general population.

[Neurological complications of the human immunodeficiency virus (HIV) infection]. / Complicaciones neurológicas de la infección por el virus de la inmunodeficiencia humana.

Human immunodeficiency virus infection (HIV) is entering into its third decade affecting more than 40 million persons on the plane, with an extraordinary incidence in the underdeveloped world, especially in the African continent where more than 25 million are affected, with more than 3 million new yearly infections and where the life expectancy is at 47 years. Although the vaccination is still far away, the introduction of combined antiretroviral therapy in the middle of the 90's was an important advance that contributed to converting an infection that previously had a very high rate of short-term mortality into a chronic disease. The neurological complications of this infection vary enormously. They affect any location of the neuroaxis and can appear at any stage of infection. It is not rare that more than one neurological complication exists. Such complications may be a consequence of the infection itself (primary) or related with immune depression accompanying it (secondary). Among the former, dementia associated to HIV and peripheral polyneuropathy stand out. Among the latter, opportunistic viral and fungal infections and lymphoma of the nervous systems stand out. In recent years different tests that help to establish the diagnoses of these entities have been developed, a necessary step to initiate adequate therapies. The immune state of the patient, reflected by the peripheral count of CD4 lymphocytes and serum viral load, helps us to establish the most likely causes of the neurological problems that appear in the context of this infection. We briefly review the most outstanding characteristics of each one of them in this work.

[Cannabis and cerebrovascular disease]. / Cannabis y patología vascular cerebral.

INTRODUCTION: Drug use is a well-kown risk factor for cerebrovascular disease in young people. Cannabis is the most widely consumed among the illicit drugs worldwide, but it has only exceptionally been associated to cerebrovascular disease. CLINICAL CASE: We here describe 2 young patients (26 and 29 years, respectively) who suffered from ischemic stroke in temporal relation with cannabis consumption. CONCLUSIONS: The review of the literature on this topic reveals another 18 patients with stroke in association to cannabis use. They all were young people with ischemic stroke. Although a causal relationship is difficult to establish due to the widespread use of cannabis, this drug may play an etiologic role in ischemic stroke.

EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task force.

Despite being a considerable problem in neurological practice and responsible for one-third of seizure-related admissions, there is little consensus as to the optimal investigation and management of alcohol-related seizures. The final literature search was undertaken in September 2004. Consensus recommendations are given graded according to the EFNS guidance regulations. To support the history taking, use of a structured questionnaire is recommended. When the drinking history is inconclusive, elevated values of carbohydrate-deficient transferrin and/or gammaglutamyl transferase can support a clinical suspicion. A first epileptic seizure should prompt neuroimaging (CT or MRI). Before starting any carbohydrate containing fluids or food, patients presenting with suspected alcohol overuse should be given prophylactic thiamine parenterally. After an alcohol withdrawal seizure (AWS), the patient should be observed in hospital for at least 24 h and the severity of withdrawal symptoms needs to be followed. For patients with no history of withdrawal seizures and mild to moderate withdrawal symptoms, routine seizure preventive treatment is not necessary. Generally, benzodiazepines are efficacious and safe for primary and secondary seizure prevention; diazepam or, if available, lorazepam, is recommended. The efficacy of other drugs is insufficiently documented. Concerning long-term recommendations for non-alcohol dependent patients with partial epilepsy and controlled seizures, small amounts of alcohol may be safe. Alcohol-related seizures require particular attention both in the diagnostic work-up and treatment. Benzodiazepines should be chosen for the treatment and prevention of recurrent AWS.

Recurrent stroke associated with cannabis use.

Drug misuse represents a risk factor for cerebrovascular disease, especially among young people. Despite the fact that cannabis is the most widely used illicit drug, there are only a few reports associating its use with cerebrovascular disease. We describe a patient who suffered three ischaemic strokes immediately after cannabis consumption. Other stroke aetiologies were ruled out, and neuroimaging revealed infarcts in different arterial areas as well as evidence of non-atherosclerotic arterial disease, which suggests an underlying vasculopathy of uncertain (toxic or inflammatory) origin. Cannabis use may be associated with ischaemic stroke in young patients, but its mechanism is unclear.

[Acute confusional state secondary to transient headache and neurological deficits with cerebrospinal fluid lymphocytosis]. / Estado confusional agudo secundario a síndrome de cefalea y déficit neurológicos transitorios con linfocitosis en líquido cefalorraquídeo.

Pseudomigraine with pleocytosis (now referred to as syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis, IHS ICHD-II code 7.8) is only infrequently accompanied by a confusional state and no cases have been described so far in association with severe agitation. We report on a patient who suffered from two episodes of headache with transient focal neurological deficits that were consistent with pseudomigraine with pleocytosis but that were followed by an intense confusional, agitated state that required admission in the intensive care unit. This possibility should be included in the differential diagnosis of confusional, agitated states.

Quality of life in migraine patients: a qualitative study.

The impact of migraine on quality of life has been traditionally evaluated by quantitative analysis, but diverse aspects remain insufficiently assessed, so a complementary qualitative approach may have advantages. The aim of this study was to assess the impact of migraine on the quality of life of migraineurs through the perception of patients and their relatives, and healthcare professionals. Qualitative methods were used, including six focus groups and nine personal interviews with 33 migraine patients under physician-directed treatment, five self-medicated patients, five relatives of migraine patients and seven healthcare professionals. Migraine has a negative affect on the quality of life, including physical, emotional and social aspects of daily life such as family, work and social relationships. Family environment and psychological well-being of patients were the aspects most affected according to patients and relatives. Health professionals emphasized work impairment and focused on pharmacological management and on the need for adequate information about migraine for non-medicated patients and patients' relatives. Qualitative methods, such as focus groups and interviews, are a valuable resource for assessing quality of life and well-being of migraine patients. These techniques open up new areas for further research.