New-Onset Movement Disorders Associated with COVID-19.

Introduction: Movement disorders are increasingly described in hospitalized and milder cases of SARS-CoV-2 infection, despite a very low prevalence compared to the total patients. Methods: We reviewed the scientific literature published in English, spanning from the initial descriptions of COVID-19 until January 25, 2021, in the PubMed/MEDLINE database. Results: We identified 93 new-onset movement disorders cases (44 articles) from 200 papers screened in the database or reference lists. Myoclonus was present in 63.4% (n = 59), ataxia in 38.7% (n = 36), action/postural tremor in 10.8% (n = 10), rigid-akinetic syndrome in 5.38% (n = 5), oculomotor abnormalities in 20.4% (n = 19), catatonia in 2.1% (n = 2), dystonia in 1.1% (n = 1), chorea in 1.1% (n = 1), functional (psychogenic) movement disorders in 3.2% (n = 3) of the reported COVID-19 cases with any movement disorder. Encephalopathy was a common association (n = 37, 39.78%). Discussion: Comprehensive neurophysiological, clinical, and neuroimaging descriptions of movement disorders in the setting of SARS-CoV-2 infection are still lacking, and their pathophysiology may be related to inflammatory, postinfectious, or even indirect mechanisms not specific to SARS-CoV-2, such as ischemic-hypoxic brain insults, drug effects, sepsis, kidney failure. Cortical/subcortical myoclonus, which the cited secondary mechanisms can largely cause, seems to be the most common hyperkinetic abnormal movement, and it might occur in association with encephalopathy and ataxia. Conclusion: This brief review contributes to the clinical description of SARS-CoV-2 potential neurological manifestations, assisting clinical neurologists in identifying features of these uncommon syndromes as a part of COVID-19 symptomatology. Highlights: - Movement disorders are probably uncommon neurological manifestations in SARS-CoV-2 infection;- Myoclonus is the most reported movement disorder associated with COVID-19, its clinical complications or pharmacological management;- The pathophysiology is yet not well-understood but can include systemic inflammation, autoimmune mechanisms, or hypoxia.

Movement disorders in children with congenital Zika virus syndrome.

BACKGROUND: Congenital Zika Virus Syndrome (CZVS) denotes the neurologic and developmental sequelae of congenital infection of the Zika virus. While prior studies have detailed the associated clinical phenotypes, new findings continue to be identified. Abnormal postures and movements have been previously described in children with CZVS, but not in detail. OBJECTIVE: To examine a cohort of infants with CZVS and characterize the spectrum of motor abnormalities, especially movement disorders. DESIGN: Cross-sectional prospective study of 21 infants with confirmed CZVS. SETTING: Single-center cohort of 32 patients with serologically confirmed CZVS cared for in a referral center in Brazil. PARTICIPANTS: 21 children (67% female), evaluated by two child neurologists and one movement disorders specialist, with clinical and laboratory diagnosis of CZVS aged between 16 and 30 months, with a mean age of 16 months at the time of the last examination. MAIN OUTCOME(S) AND MEASURE(S): Prospective neurologic examination by a team of three neurologists, including one movement disorders specialist. Sixteen (76.2%) children had a longitudinal evaluation with a six-month interval. The same team of experts analyzed recorded videos of all patients to characterize motor abnormalities and movement disorders. Neuroimaging findings were also analyzed to correlate with clinical findings. RESULTS: Twenty (95.2%) patients presented with dystonic postures, including "125" posture of the fingers in 17 (80.1%), "swan neck" posture of the fingers in three (18.8%), oromandibular dystonia in nine (42.9%), extensor axial hypertonia in eight (38.1%) and internal rotation of the shoulder posture in two (9.5%). Four (19%) patients had tremor. All children had malformations of cortical development, and in 13 (61.9%), the pattern was consistent with a severe and diffuse gyral simplification. Seventeen children (81%) had calcification in the transition of grey and white matter, whereas 11 (52.4%) patients had basal ganglia calcifications. CONCLUSION AND RELEVANCE: In our series, dystonic postures and other extrapyramidal signs were frequent and potentially disabling. Although children with CZVS are assessed and treated for spasticity, dystonia and other movement disorders remain neglected. This study emphasizes that extrapyramidal findings may potentially influence optimal strategies for rehabilitation and management.

Sleep disorders in aging polio survivors: A systematic review.

BACKGROUND: Sleep disturbances, especially sleep disordered breathing and sleep movement disorders, seem to be highly prevalent among aging polio survivors. They could contribute to late functional deterioration, fatigue, poor quality of life and negative health outcomes, thereby increasing cardiovascular risk. OBJECTIVES: This review focused on current knowledge of the prevalence of sleep disorders in polio survivors, their features, predictive factors and management. DATA SOURCES: Articles were searched in PubMed and the Cochrane Library up to March 2018. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Articles needed to 1) be written in English; 2) include only participants with previous poliomyelitis or post-polio syndrome diagnosis; and 3) involve any form of sleep disorders. Articles about isolated fatigue or non-specific sleep complaints as well as non-polio specific articles (neuromuscular disorders) were not included in the qualitative analysis. RESULTS: Among 166 studies identified, 41 were included in this review. The prevalence of sleep apnea syndrome, nocturnal alveolar hypoventilation and restless legs syndrome seemed higher than in the general population (from 7.3% to 65%, 15% to 20% and 28% to 63%, respectively). This review highlights the lack of randomised studies assessing sleep disorder management in this specific population. LIMITATIONS: Because of the small number of eligible publications, none was excluded for methodological limitations, and only a qualitative analysis was provided. CONCLUSIONS AND IMPLICATIONS: Follow-up of polio survivors should include systematic screening for sleep disorders because they are associated with adverse consequences. Sleep disorder evaluation and management should improve the long-term survival and quality of life of polio survivors. Methodologically robust clinical trials are needed, but the decreasing prevalence and large clinical spectrum of the disease may complicate the creation of comparable groups.

Movement disorder: a manifestation of HIV and its response to therapy.

Both akinetic and hyperkinetic movement disorders may rarely be the presenting feature of human immunodeficiency virus (HIV) infection. The possible pathogenic basis is the involvement of subcortical structures by the HIV infection-related pathology. Opportunistic infections, or mass lesions complicating HIV infection. In addition dopaminergic dysfunction and medications may also play a role. We report a HIV infected male who presented with progressive choreoathetoid movements and dystonia. He had remarkable improvement of the movement disorder with tetrabenazine and anti-retroviral therapy (HAART) treatment.

Poliovirus antibody levels and lameness among individuals in three regions of Ghana.

Introduction: Ghana recorded the last case of poliomyelitis caused by wild poliovirus in 2008 and the country was declared polio-free in 2015. Polio-neutralizing-antibody levels in the population of three geographically representative regions of Ghana was determined, to identify possible immunity gaps. Methods: Cross-sectional, hospital (1-70 years old) and school (primary, 1-15 years old)-based studies were undertaken in three regions in 2016. Individuals who visited the three teaching hospitals of the regions and were referred for haematology investigations were invited to participate in our study. Neutralizing-antibody titers to polio serotypes P1, P2, and P3 were assayed by WHO-standards. Antibody titers of ≥8 were considered protective. In the school lameness survey, clinical and epidemiological data were obtained from parents and their lamed children. Bivariate and multivariate analyses were conducted on subject characteristics, to assess potential factors for failure to seroconvert. P-values < 0.05 were considered statistically significant. Results: Neutralizing-antibodies against poliovirus types 1, 2 and 3 were detected in 86% (264/307), 84% (258/307) and 75% (230/307) of the samples, respectively. Overall, 60.1% (185/307) were seropositive for the three polio serotypes and 2.9% (9/307) were seronegative. Polio neutralizing-antibodies (P1and P2) decreased with age (p < .001). Low seroprevalence of polio-neutralizing-antibodies was significantly associated with low school attendance of mothers (p < .001). Prevalence of residual paralysis was <1.0/1,000 among the school children. Conclusion: Our study population is moderately protected against the three poliovirus serotypes. However, immunity appears to be lower with a higher age and low mother's education. This may suggest the need for young-adult booster-dose to minimize the risk of wild poliovirus infection.

Suspected herpes encephalitis and opercular syndrome in childhood.

Herpes simplex encephalitis is the most common form of sporadic viral encephalitis. It may occur at any age, giving rise to a syndrome with a high morbidity and mortality. Its presentation may be atypical, and the initial complementary investigations nonspecific, making early diagnosis difficult and thus worsening its prognosis. This report describes four infants with herpes encephalitis presenting with an opercular syndrome that left significant sequelae after the acute episode. The opercular syndrome is characterized clinically by a disturbance of voluntary control of the facio-linguo-glosso-pharyngeal muscles, affecting speech and swallowing. Recognition of the opercular syndrome as a form of presentation of herpes encephalitis enables early diagnosis to be made in these patients, with the rapid initiation of treatment with acyclovir, improving the clinical course.

RANTES, MDC and SDF-1alpha, prevent the HIVgp120-induced food and water intake decrease in rats.

Human immunodeficiency virus (HIV)-wasting syndrome might be facilitated by the HIVgp120 affecting the immunological system. We studied the effect (subchronic administration: 5 days) of HIVgp120, and a few immune-response mediators: regulated upon activation normal T-cell expressed and presumably secreted (RANTES), stromal derived factor-1alpha (SDF-1alpha), macrophage-derived chemokine (MDC), and their combination, on food and water intake in rats, motor control and pain perception. Eighty male adult Wistar rats received an intracerebroventricular (icv) administration of: vehicle 5 microl/day or 0.92 nmol daily of HIVgp120IIIB, RANTES, SDF-1alpha, or MDC, and the combination of RANTES+HIVgp120IIIB, SDF-1alpha+HIVgp120IIIB, or MDC+HIVgp120IIIB. Food and water intake was measured every day during administration, and 24 and 48 h after the last administration. Rats were also weighed the first and the last day of experiment in order to detect the impact of these treatments in the body weight. HIVgp120IIIB significantly decreased food and water intake. These rats gain less weight than the control (vehicle) and chemokines-treated subjects with exception of those treated with SDF-1alpha that also gain less weight. In addition, HIVgp120 deteriorated motor control. HIVgp120IIIB effects on food and water intake, and motor control were prevented by these chemokines. HIVgp120+RANTES, HIVgp120+SDF-1alpha, and SDF-1alpha alone induced hyperalgesia. Results suggest an interaction between HIVgp120 and the chemokine system to generate the HIV-wasting syndrome, the motor abnormalities and changes in pain perception.

Balance and gait abnormalities of a child with West Nile virus infection.

We describe a case of a previously healthy 2-year-old female patient with rash, fever and vomiting for 10 days who presented for medical attention with acute profound balance and gait disturbances and intentional movement dysmetria. West Nile virus-specific IgM and IgG antibodies were detected in the patient's cerebrospinal fluid.

Borna disease virus infection of adult and neonatal rats: models for neuropsychiatric disease.

Animal models provide unique opportunities to explore interactions between host and environment. Two models have been established based on Borna disease virus infection that provide new insights into mechanisms by which neurotropic agents and/or immune factors may impact developing or mature CNS circuitry to effect complex disturbances in movement and behavior. Note in press: Since this chapter was submitted, several manuscripts have been published that extend findings reported here and support the relevance of BDV infections of neonatal Lewis rats as models for investigating mechanisms of neurodevelopmental damage in autism. Behavioral abnormalities, including disturbed play behavior and chronic emotional overactivity, have been described by Pletnikov et al. (1999); inhibition of responses to novel stimuli were described by Hornig et al. (1999); loss of Purkinje cells following neonatal BDV infection has been demonstrated by Eisenman et al. (1999), Hornig et al. (1999), and Weissenböck et al. (2000); and alterations in cytokine gene expression have been reported by Hornig et al. (1999), Plata-Salaman et al. (1999) and Sauder et al. (1999).

Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings.

BACKGROUND: We tested whether metabolic abnormalities in the prefrontal-striatal circuitry as demonstrated by positron emission tomography (PET) were present in patients seropositive for human immunodeficiency virus type 1 (HIV-1) with HIV-1-associated minor motor deficits as demonstrated by quantitative motor testing. PATIENTS: We examined 19 HIV-1-positive patients, covering the range from normal results of quantitative motor testing to clearly pathologic psychomotor slowing indicative of HIV-1-associated minor motor deficits. None fulfilled the clinical criteria for HIV-1-associated dementia. Results were compared with those of 15 healthy volunteers. METHODS: All subjects underwent clinical examination, routine magnetic resonance (MR) imaging, and electrophysiologic motor testing at the time of PET. RESULTS: Seven HIV-1-positive patients showed significant hypermetabolism in the basal ganglia. Nine patients showed a significant frontomesial hypometabolism. CONCLUSIONS: The data of our cross-sectional study strongly suggest a characteristic time course in the development of HIV-1-associated minor motor deficits. Hypermetabolism in the basal ganglia is associated initially with normal motor performance. Moderate motor slowing appears at a later stage when basal ganglia hypermetabolism drops toward hypometabolism. More severe functional deficits and highly pathologic motor slowing become manifest when hypometabolism is most widespread in the basal ganglia. This stage leads to dementia.

Paroxysmal dyskinesias in patients with HIV infection.

OBJECTIVE: To determine the clinical features of paroxysmal dyskinesias among HIV type 1 (HIV-1)-seropositive patients. BACKGROUND: Movement disorders have been associated with HIV infection, although the full spectrum of these disorders remains uncertain. METHODS: Six adult HIV-1-seropositive patients presenting with paroxysmal dyskinesias were identified. Each patient underwent metabolic, CSF, EEG, and neuroimaging studies. RESULTS: Mean age at onset was 34.5 years and five of six patients were AIDS defined. Dyskinesias were focal, multifocal, or hemidystonic in four patients and generalized in another two patients. Two of the six patients had paroxysmal kinesigenic dyskinesias and the remaining four patients had paroxysmal nonkinesigenic dyskinesias. Choreoathetosis (n = 3), myoclonus (n = 2), postural tremor (n = 5), and dysarthria (n = 3) were observed. Benzodiazepines appeared beneficial in three of six patients. Two patients with HIV-associated dementia and paroxysmal nonkinesigenic dyskinesia had a progressive course to death. Autopsy of a patient with paroxysmal nonkinesigenic dyskinesias revealed intense astrogliosis and loss of calbindin-positive neurons in the subcortical gray matter. CONCLUSIONS: Paroxysmal dyskinesias may present as a primary HIV-1-induced neurologic syndrome. The occurrence of paroxysmal dyskinesias is associated with neuronal injury and loss in the subcortical gray matter but the mechanism remains unknown.

Movement disorders in Japanese encephalitis.

Movement disorders in Japanese encephalitis (JE), although reported, have not been analyzed systematically. In this study, we report an analysis of movement disorders in 14 out of 17 JE patients, correlated with the radiological findings. All patients had at least a four fold rise of IgG antibodies against JE in a haemagglutination inhibition test. The patients' ages ranged between 2 and 54 years and 4 of them were women. Extrapyramidal signs, such as hypokinesia, hypophonia and masking of the face, were present in all patients by the first month as the patients came out of the coma-except for 1 patient. Eight patients had axial and 3 tongue dyskinesia; rigidity was present in 6 and tremor in 2 patients. At 3 months, these symptoms improved considerably in 6 patients. Cranial CT scan revealed thalamic involvement in 10, which was bilateral in 9 patients. Two patients had brain stem and one had cerebellar involvement. Cranial MRI was carried out in 9 patients and revealed additional findings in lentiform nucleus, midbrain and pons in 3 each and cerebellum in 4 patients. Bilateral thalamic involvement on MRI was seen in all the patients, including two patients whose CT scans were normal. SPECT studies using 99mTc-ECD revealed bilateral thalamic hypoperfusion in all (n = 7) and frontal hypoperfusion in 3 patients. In JE, movement disorders are common and may be due to thalamic involvement in isolation or in combination with basal ganglia or midbrain or both.

Painful legs and moving toes syndrome associated with herpes zoster myelitis.

A 75-year-old woman developed painful legs and moving toes syndrome (PLMT) 16 months after the onset of herpes zoster (HZ) myelitis. Although the scattered extensive lesions due to HZ myelitis were observed to be eccentric near the posterior horn on MRI, these changes had disappeared upon the development of PLMT. Combined median and tibial nerve somatosensory evoked potentials demonstrated abnormal findings only in the tibial nerve stimuli, suggesting that a severe alteration occurred in the somatosensory fibers coming selectively from the lower legs. These findings suggest plasticity in the ascending somatosensory pathway including the posterior horn cells, probably involving the interneuron networks, for the lower legs may underlie the development of PLMT associated with HZ myelitis.

Movement disorders and AIDS: a review.

Movement disorders are a potential neurologic complication of acquired immune deficiency syndrome (AIDS), and may sometimes represent the initial manifestation of HIV infection. Dopaminergic dysfunction and the predilection of HIV infection to affect subcortical structures are thought to underlie the development of movement disorders such as parkinsonism in AIDS patients. In this review, we will discuss the clinical presentations, etiology and treatment of the various AIDS-related hypokinetic and hyperkinetic movement disorders, such as parkinsonism, chorea, myoclonus and dystonia. This review will also summarize current concepts regarding the pathophysiology of parkinsonism in HIV infection.

Movement disorders in the tropics.

The spectrum of movement disorders in the tropics is different from that seen in the industrialized nations of the west. This is not surprising given the unique combination of environmental and population characteristics in the tropics. Infections seldom encountered in the west such as tuberculous meningitis, typhoid fever, Japanese encephalitis, malaria, trypanosomiasis or cysticercosis are often seen in the tropics and with global patterns of travel and immigration these conditions are becoming more common worldwide. Movement disorders associated with these infections, HIV, slow virus and prion disease are discussed. Taking into account the diverse etiologies of movement disorders in the tropics, movement disorders with a nutritional basis such as the infantile tremor syndrome, seasonal ataxia and tropical ataxic neuropathy, and manganese neurotoxicity are also reviewed. Finally, certain special characteristics of ubiquitous disorders such as Parkinson's disease, and disorders with a genetic basis such as Wilson's disease and spinocerebellar degeneration are described.

Hemiballismus associated with Influenza A infection.

A case of 2-year and 3-month-old boy developing right hemiballismus and transient selective unilateral involvement in the left thalamus on MRI during Influenza A infection is reported. Hemiballismus is an extremely rare neurological complication and, to our knowledge, this is the first case showing hemiballismus during Influenza A infection.

Influenza A encephalitis with movement disorder.

Influenza A is an uncommon but well-recognized cause of viral encephalitis in childhood, occurring most commonly during community influenza outbreaks. The authors report four cases of influenza A encephalitis that occurred during an Australian epidemic in 1997-1998. Choreoathetosis during the acute phase of infection or basal ganglia involvement on neuroimaging was observed in three of the four patients. These findings in pediatric encephalitis are suggestive of influenza A infection and may guide investigation and early diagnosis.

Subtle neuropsychological impairment and minor cognitive-motor disorder in HIV-1 infection. Neuroradiological, neurophysiological, neuroimmunological, and virological correlates.

HIV-1 infection of brain may be associated with multiple treatment targets, only the most severe of which is represented by HAD. Focusing on earlier treatment targets such as MCMD and cognitive-motor impairment in the absence of any clinical disorder (as well as neuroprotection) may prove to be of greater clinical utility in the treatment and prevention of such impairment than a focus on later-stage cognitive-motor disease, when neuronal cell death is already extensive. This may be especially important now that improvements using the protease inhibitors in triple-drug combination regimens have reduced plasma viral load to unmeasurable levels, while these drugs do not penetrate the CSF well. Currently, peripheral blood markers do not appear to be highly sensitive for central nervous system impairment, and specific CSF laboratory markers have some limited value at present-while requiring a lumbar puncture to obtain. Hence, a role for noninvasive techniques using neuroimaging exists in the clinical management of HIV-1-infected patients. To date, structural imaging techniques have proven limited in value for HIV-1-specific impairment. Several functional techniques (PET, SPECT, and MR spectroscopy) have now provided promising results for the purposes of identifying clinically significant dysfunction, relating such dysfunction to clinical neuropsychiatric symptom status, and for treatment response monitoring. Further studies are needed to examine the extent to which such imaging modalities not only parallel clinically relevant aspects of HIV-1 disease progression, but also match specific types of neuropsychologic performance deficits with potential significance for neuroanatomical localization. It is particularly important to include neurophysiological, neuroimmunological, and virological measures in studies that examine clinical neuropsychiatric status with neuroimaging techniques. In addition, the inclusion of neuropathology data, where possible, is important because demonstration of HIV-1 encephalitis cannot be equated with clinical disorder and because specific HIV-1-associated pathological changes have not yet been proven to be assessed well with neuroimaging techniques (e.g., the extent of microglial cell and macrophage activation). Also, treatment response studies are needed in conjunction with primary antiretroviral therapy regimens specifically aimed at central nervous system penetration (e.g., GW1592, GW141, and nevirapine). The results of such work will provide the data required to determine whether these promising functional neuroimaging techniques will aid in meeting the expected, imminent increase in clinical burden of this frequent complication of HIV-1 infection.

Detection of enteroviruses in cases of neurological disorders in the State of Pará, Brazil.

Eighty-one cerebrospinal fluid (CSF) samples mainly from cases of aseptic meningitis and motor deficiency syndrome were sent to the Virology Section of Evandro Chagas Institute, Belém Pará, in the period of January 1995 to January 1996 in order to isolate viruses. All samples were inoculated onto HEp-2 cell culture and newborn mice, with negative results. The probability of isolating viruses by these methods is reduced because of the low concentration of viral particles in these specimens. In order to obtain more information about the etiology of these cases, a group of 23 samples were selected to be tested by a more sensitive technique than the virus isolation - the reverse transcription polymerase chain reaction (RT-PCR). Specific primers directed to conserved regions in the enterovirus genome were used, considering that this group of viruses is frequently associated with these neurological disorder. The age of the patients ranged from 1 to 55 years and nearly all of them lived in Belém, State of Pará, North of Brazil. Of 15 samples analyzed by RT PCR nine (60%) were positive; of these, 6 (66.6%) had motor deficiency and 3 (33.3%) developed aseptic meningitis. These results show that it is important to investigate enterovirus as cause of these syndromes.

Neurologic manifestations and outcome of West Nile virus infection.

CONTEXT: The neurologic manifestations, laboratory findings, and outcome of patients with West Nile virus (WNV) infection have not been prospectively characterized. OBJECTIVE: To describe prospectively the clinical and laboratory features and long-term outcome of patients with neurologic manifestations of WNV infection. DESIGN, SETTING, AND PARTICIPANTS: From August 1 to September 2, 2002, a community-based, prospective case series was conducted in St Tammany Parish, La. Standardized clinical data were collected on patients with suspected WNV infection. Confirmed WNV-seropositive patients were reassessed at 8 months. MAIN OUTCOME MEASURES: Clinical, neurologic, and laboratory features at initial presentation, and long-term neurologic outcome. RESULTS: Sixteen (37%) of 39 suspected cases had antibodies against WNV; 5 had meningitis, 8 had encephalitis, and 3 had poliomyelitis-like acute flaccid paralysis. Movement disorders, including tremor (15 [94%]), myoclonus (5 [31%]), and parkinsonism (11 [69%]), were common among WNV-seropositive patients. One patient died. At 8-month follow-up, fatigue, headache, and myalgias were persistent symptoms; gait and movement disorders persisted in 6 patients. Patients with WNV meningitis or encephalitis had favorable outcomes, although patients with acute flaccid paralysis did not recover limb strength. CONCLUSIONS: Movement disorders, including tremor, myoclonus, and parkinsonism, may be present during acute illness with WNV infection. Some patients with WNV infection and meningitis or encephalitis ultimately may have good long-term outcome, although an irreversible poliomyelitis-like syndrome may result.