Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

Olfactory vector hypothesis for encephalitis lethargica.

Viruses have long been implicated in the pathogenesis of classical encephalitis lethargica, which was first described by Constantin von Economo in 1917. In this article, I propose the hypothesis that an airborne virus travels along the olfactory conduit to infect the olfactory bulb; this local infection or induced neuroinflammation, in turn, retrogradely targets certain neuronal populations with sleep-wake regulatory functions in the hypothalamus and midbrain, leading to the development of wakeful inactivity, a hallmark clinical feature of the disease. Furthermore, the olfactory vector hypothesis may also explain the pathomechanism of the debilitating complication of the disease, i.e., postencephalitic parkinsonism, in terms of a recently discovered nigro-olfactory projection.

Postencephalitic parkinsonism: interesting clinico-imaging correlation.

IMPORTANCE: Post-encephalitic parkinsonism (PEP) is believed to be caused by a viral illness which causes degeneration of the nerve cells in the substantia nigra, resulting in clinical parkinsonism. Although common during the period of the First World War, the diagnosis of PEP is rarely entertained today. OBSERVATION: We report an adolescent boy of PEP, who was bedridden due to severe parkinsonism following the encephalitis attack. After relevant imaging and investigation, he was treated with levodopa which made him independent from a year long total dependent condition. RELEVANCE AND CONCLUSION: Encephalitis lethargica or PEP is one of the rare parkinsonian syndromes which may be amenable to treatment. Proper diagnosis and treatment may help the patient become ambulatory from the dreaded lethargic condition.

Oscilaciones cerebrales: papel fisiopatológico y terapéutico en algunas enfermedades neurológicas y psiquiátricas / Brain oscillations: pathophysiological and therapeutic role in some neurological and psychiatric diseases

Se usa el término «oscilación o actividad oscilatoria» para referirse a las fluctuaciones rítmicas de los potenciales postsinápticos de un grupo neuronal (potenciales de campo local) o de una región cortical (EEG, electrocorticografía) y también al patrón de descarga rítmico de los potenciales de acción de una neurona o un grupo neuronal. La actividad oscilatoria posibilita la sincronización entre grupos neuronales de la misma área cortical o de áreas distantes entre sí que intervienen en una acción motora, tarea cognitiva o perceptiva. Con frecuencia es motivo de confusión asociar la presencia de actividad oscilatoria con fenómenos de sincronización, ya que ambos fenómenos aunque relacionados no son equivalentes. En patologías neurológicas o psiquiátricas tan distintas como la enfermedad de Parkinson u otros movimientos anormales, la epilepsia o la esquizofrenia se han descrito anomalías de la actividad oscilatoria de distintas estructuras cerebrales o de su sincronización que podrían jugar un papel relevante en su fisiopatología. En esta revisión se discuten estos aspectos haciendo hincapié en su importancia por ser un mecanismo básico del funcionamiento cerebral y un nuevo mecanismo fisiopatólogico de la sintomatología de algunas enfermedades cerebrales (AU)

The terms «oscillations» or «oscillatory activity» are frequently used not only to define the rhythmic fluctuations of the postsynaptic potentials of a neuronal group (local field potentials) or a cortical region (EEG, MEG), but also to indicate the rhythmic discharge pattern of action potentials from a neuron or a small group of neurons. Oscillatory activity makes possible the synchronization of different neuronal groups from nearby or distant cortical regions that participate in the same motor, sensory or cognitive task. The presence of oscillatory activity is usually associated to the existence of synchronization, but both phenomena are not necessarily always equivalent. Abnormalities of oscillatory activities or synchronization within or between different brain structures have been described in several neurological and psychiatric diseases; these abnormalities might play a relevant pathophysiological role in Parkinson´s disease (and other movement disorders), schizophrenia or epilepsy. This review discusses all these aspects, with emphasis on their potential role both as a basic mechanism in brain function and as a pathophysiological substrate for some of the symptoms and signs observed in several diseases (AU)

Contemporary Encephalitis Lethargica: phenotype, laboratory findings and treatment outcomes.

BACKGROUND: Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL. METHODS: Patients were diagnosed over a period of 3 years using proposed diagnostic criteria. Extensive laboratory and imaging tests were performed for exclusion of other causes. Anti-neuronal antibodies against human basal ganglia were detected with western immunoblotting and (18)F-FDG PET imaging was performed. Selected cases were videotaped. RESULTS: Our patients (M/F: 5/3) ranged from 2-28 years (mean 9.3 +/- 9.5). Encephalopathy, sleep disturbances and extrapyramidal symptoms were present in all cases. Laboratory investigations revealed CSF leukocytosis in 5/8 patients and anti-BG Ab in 4/7 patients. MRIs revealed structural abnormalities in 7/8 cases. (18)F-FDG PET showed basal ganglionic hypermetabolism in 4/7 patients. Treatment approaches included immunomodulating and symptomatic therapies. We report no mortality from EL in our series. CONCLUSIONS: There seems to be little doubt that cases of EL still occur. Diagnosis may be based on clinical suspicion and laboratory/imaging tests may lead to early initiation of immunomodulating and supporting therapies. We suggest that in addition to anti-BG Abs FDG PET should be considered as a diagnostic tool for EL.

Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options.

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

[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.

Constantin von Economo's contribution to the understanding of movement disorders.

Constantin von Economo's (CvE) main scientific achievements were his studies on the cytoarchitectonics of the cerebral cortex, sleep, and encephalitis lethargica (EL). He found a close relationship between motor symptoms and psychiatric and behavioral disorders in EL and postencephalitic Parkinsonism and identified the underlying neuropathology in the diencephalon and the brainstem. In agreement with Tretiakoff's findings in Parkinson's disease, CvE related postencephalitic Parkinsonism to neuronal loss in the substantia nigra. Several of CvE's early, less well-known publications also deal with the basal ganglia and movement disorders. He demonstrated in rabbits that the substantia nigra modulates automatization, coordination, and succession of masticatory movements and swallowing. In a study on the effects of experimental lesions of the cerebral peduncle in cats and monkeys, CvE hypothesized a corticotegmental pathway that maintains motor functions after pyramidal tract lesions. Recent studies have identified this pathway, which ends in the pedunculopontine nucleus. In a study on posthemiplegic chorea, CvE discussed various pathophysiological hypotheses that partly resemble modern concepts of chorea. In a clinicopathological study on Wilson's disease, CvE traced the striofugal fibers and visualized the basal ganglia outflow pathways. CvE was an outstanding multidisciplinary movement disorder specialist who contributed substantially to modern basal ganglia research.

Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system.

Human narcolepsy is a chronic sleep disorder affecting 1:2000 individuals. The disease is characterized by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep, such as sleep paralysis and hypnagogic hallucinations. Recently, it was discovered that the pathophysiology of (idiopathic) narcolepsy-cataplexy is linked to hypocretin ligand deficiency in the brain and cerebrospinal fluid (CSF), as well as the positivity of the human leukocyte antigen (HLA) DR2/DQ6 (DQB1*0602). The symptoms of narcolepsy can also occur during the course of other neurological conditions (i.e. symptomatic narcolepsy). We define symptomatic narcolepsy as those cases that meet the International Sleep Disorders Narcolepsy Criteria, and which are also associated with a significant underlying neurological disorder that accounts for excessive daytime sleepiness (EDS) and temporal associations. To date, we have counted 116 symptomatic cases of narcolepsy reported in literature. As, several authors previously reported, inherited disorders (n=38), tumors (n=33), and head trauma (n=19) are the three most frequent causes for symptomatic narcolepsy. Of the 116 cases, 10 are associated with multiple sclerosis, one case of acute disseminated encephalomyelitis, and relatively rare cases were reported with vascular disorders (n=6), encephalitis (n=4) and degeneration (n=1), and hererodegenerative disorder (three cases in a family). EDS without cataplexy or any REM sleep abnormalities is also often associated with these neurological conditions, and defined as symptomatic cases of EDS. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, review of the literature reveals numerous unquestionable cases of symptomatic narcolepsy. These include cases with HLA negative and/or late onset, and cases in which the occurrences of the narcoleptic symptoms are parallel with the rise and fall of the causative disease. A review of these cases (especially those with brain tumors), illustrates a clear picture that the hypothalamus is most often involved. Several cases of symptomatic cataplexy (without EDS) were also reported and in contrast, these cases appear to be often associated with non-hypothalamic structures. CSF hypocretin-1 measurement were also carried out in a limited number of symptomatic cases of narcolepsy/EDS, including narcolepsy/EDS associated with tumors (n=5), head trauma (n=3), vascular disorders (n=5), encephalopathies (n=3), degeneration (n=30), demyelinating disorder (n=7), genetic/congenital disorders (n=11) and others (n=2). Reduced CSF hypocretin-1 levels were seen in most symptomatic narcolepsy cases of EDS with various etiologies and EDS in these cases is sometimes reversible with an improvement of the causative neurological disorder and an improvement of the hypocretin status. It is also noted that some symptomatic EDS cases (with Parkinson diseases and the thalamic infarction) appeared, but they are not linked with hypocretin ligand deficiency. In contrast to idiopathic narcolepsy cases, an occurrence of cataplexy is not tightly associated with hypocretin ligand deficiency in symptomatic cases. Since CSF hypocretin measures are still experimental, cases with sleep abnormalities/cataplexy are habitually selected for CSF hypocretin measures. Therefore, it is still not known whether all or a large majority of cases with low CSF hypocretin-1 levels with CNS interventions, exhibit EDS/cataplexy. It appears that further studies of the involvement of the hypocretin system in symptomatic narcolepsy and EDS are helpful to understand the pathophysiological mechanisms for the occurrence of EDS and cataplexy.

Yawning?

Since antiquity yawning has attracted a moderate interest among philosophers, psychologists, physiologists, as well as educators, moralists and physicians. Organisms from birds to men and from the womb to the deathbed were found to be displaying it. While sometimes satisfying to the producer, its display is offensive to the lay observer. Hippocrates had it on his lists of useful 'natures.' Aristotle dropped a few words on the matter. Boerhaave elevated its function to the intellect of animals. Haller has commented on its relation to the acoustic system, blood-flow, and baby sleep. Darwin mentioned it in connection with emotional behavior. Some modern authors praised its beneficial effects on respiration and smell. In the 1960s, Ashley Montagu tried to correct the contemporary failure to explain the behavior by the fact of raised CO2 and arterial compression. It also interested some neurologists, especially in its association with the encephalitis lethargica in the 1920s, with 'spasmodic yawning,' with epilepsy, not to speak of hysteria. As to boredom or its stimulus, a 40-page dissertation survives from the court of Frederick the Great of the 18th century condemning idleness, a subject that also inspired Blaise Pascal and William James. But in the Hindu world, public yawning was a religious offense.

von Economo encephalitis.

In April 1917, Dr Constantin von Economo presented his clinical and pathologic findings of a new disease--soon to be part of a worldwide epidemic--before the Vienna Psychiatric Society. He named it encephalitis lethargica. After years of careful observation, he collected and analyzed thousands of cases and classified them into 3 clinical syndromes: somnolent-ophthalmoplegic, hyperkinetic, and amyostatic-akinetic forms. He described the now legendary postencephalitic Parkinsonism, noting that symptoms could emerge years after the original infection, often without signs of prodromal "flu." He emphasized the neuropathologic findings: inflammatory changes in the tegmentum of the midbrain accounting for the sleep disturbance and ocular signs. After encountering sporadic cases following the epidemic, he concluded that the somnolent-ophthalmoplegic syndrome was the primary expression of encephalitis lethargica. This article outlines the observations and conclusions of Dr von Economo during and after the epidemic through seminal quotations primarily from his published works, as well as from more recent reports.

Ante litteram description of atypical parkinsonian cases.

We have searched in the neurological literature for cases of atypical parkinsonism published before the epidemic encephalitis era. Some of these cases can be recognized. Therefore the epidemic encephalitis has no etiological importance in these clinical syndromes.

El triste final prematuro de la pianista chilena Rosa Renard Artigas 1894-1949 / The sad and premature ending of the chilean pianist Rosa Renard Artigas 1894-1949

Se analiza en forma restrospectiva la enfermedad neurológica que terminó prematuramente con la vida de Rosa Renard Artigas a los 55 años de edad. Ella fue conocida y admirada internacionalmente como una notable pianista y su muerte ocurrió 4 meses después de su triunfo presentación en el Carnegie Hall de Nueva York. El diagnóstico de encefalitis letárgica hecho por su médico personal aparece muy cuestionable, dados el comienzo subagudo y las manifestaciones neurológicas que son muy discordantes con lo descrito como signos característicos de la encefalitis letárgica por Von Economo. En cambio, la probabilidad de una posible enfermedad de Creutzfeldt-Jakob es altamente sugerente en este caso

Arterial oxygen saturation in severely disabled people: effect of oral feeding in the sitting position.

Control of the circulatory and respiratory systems is especially important in severely disabled people. The purpose of this study was to clarify the response of hemoglobin oxygen saturation level (SpO(2)), pulse rate, and respiratory rate during oral feeding in severely disabled persons. Continuous measurement of these variables was done by pulse oximetry and respiratory inductance plethysmography under two experimental settings in eight severely disabled persons aged 14-28 yrs. Setting I consisted of the following three procedures: (a) a 30-min period in the supine position, (b) a 50-min period in a sitting position, and (c) a 30-min period in the supine position. Setting II consisted of the following four procedures: (a) a 30-min period before the meal in the supine position, (b) a nonspecified period in a sitting position during which the meal was taken, (c) a 30-min period after the meal in the same sitting position, and (d) a 30-min period in the supine position. Results showed that mean SpO(2) level decreased and mean pulse rate increased during the meal in almost all subjects. In many cases, pulse rate and SpO(2) level did not return to baseline values in the sitting position after the meal. These findings indicate that oral feeding of severely disabled persons in a sitting position places considerable stress on the circulatory system, the effects of which may last after the meal in some cases.

Dopaminergic therapy in acute encephalitis lethargica.

We describe a patient with an acute illness, with clinical features characteristic of encephalitis lethargica, who responded repeatedly to trials of an apomorphine infusion and subsequently to oral levodopa therapy. This observation implies a direct acute neurotropic effect of the encephalitis on nigral dopaminergic cells. Dopaminergic medication may therefore be helpful in the acute stage of encephalitis lethargica as well as in the delayed post-encephalitic parkinsonian phase of the syndrome.