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.

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.

Clinical features of cerebral palsy in children with symptomatic congenital cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus is the most common cause of vertically transmitted viral infection, affecting around 1% of liveborns. Infection is symptomatic in nearly 10% of infected children who are at higher risk of development of severe neurological disorders, including cerebral palsy. AIMS: To study the clinical profile of children with cerebral palsy caused by symptomatic congenital cytomegalovirus infection in a multicenter study involving six countries from the Surveillance of Cerebral Palsy in Europe (SCPE) Network. METHODS: Data on 35 children (13 males, 22 females; mean age at last assessment 12y 6mo, age range 14y 6mo, min 4y, max 18y 6mo) on pre/peri/neonatal history and last clinical assessment were collected. Classification of cerebral palsy and associated impairments was performed according to SCPE criteria. RESULTS: The majority of children had bilateral spastic cerebral palsy, 85.7%, with a confidence interval (CI) [69.7-95.2], and 71.4% [CI 53.7-85.4] were unable to walk (GMFCS levels IV-V) while fine motor function was severely affected in 62.8% [CI 44.9-78.5] (BFMF levels IV and V). Most of the children with severe CP had severe associated impairments. 11.4% of children had severe visual and 42.8% severe hearing impairment, 77.1% [CI 59.9-89.6] suffered from epilepsy, also 77.1% had severe intellectual impairment, and speech was undeveloped in 71.4%. Female:male ratio was 1.69:1 and 80% of children were term born. CONCLUSIONS: Cerebral palsy following symptomatic congenital cytomegalovirus infection seems to be in most cases a severe condition and associated impairments are overrepresented.

[Study on the prevalence of acute flaccid paralysis and hand foot mouth disease in Beijing 2006 - 2008].

OBJECTIVE: To study the prevalence of acute flaccid paralysis (AFP) and hand foot mouth disease (HFMD) in Beijing, from 2006 - 2008. METHODS: Data on AFP and HFMD was analyzed epidemiologically, during 2006 - 2008 in Beijing. All the specimens from AFP cases were isolated and identified by RD and L20B cell and all of non-polio enterovirus (NPEV) cases were assayed by HFMD real-time PCR kit. The relationship between AFP and HFMD was analyzed. RESULTS: During 2006 - 2008, the number of AFP case in Beijing increased from 108 to 177 while the NPEV isolation rate increased from 11.11% to 20.34% and the positive rate of enterovirus 71 (EV71) and/or coxsackie virus A16 (Cox A16) increased from 0.93% to 10.17%. CONCLUSION: The prevalence of HFMD caused by EV71 and/or Cox A16 might have contributed to the increase of AFP cases in Beijing.

Spectrum of movement disorders in encephalitis.

To study the frequency and type of movement disorders and correlate these with MRI findings and outcome. Consecutive patients having encephalitis with movement disorders were included. The encephalitides were categorized into Japanese encephalitis (JE), herpes simplex, dengue, mumps, measles and nonspecific, depending on respective ELISA or CSF PCR. The movement disorders were recorded and severity was graded into mild, moderate, severe and markedly severe. Cranial MRI was done on a 1.5 T scanner acquiring T1, T2 and FLAIR sequence, and the location of MRI changes was noted. Outcome was defined at 6 months on the basis of functional status into complete, partial or poor. The type and severity of movement disorders and their relation to outcome was evaluated. Seventy-four out of 209 encephalitis patients had movement disorders; 67.6% of the patients had JE, 51.2% nonspecific and 11.3% dengue encephalitis. Their median age was 19 years and 16 were females. Parkinsonian features were present in 36, dystonia in six and both in 32 patients. The severity of movement disorders ranged between 2 and 4 (scale: none = 0, mild = 1, moderate = 2, severe = 3, markedly severe = 4). Movement disorders were common in males (P = 0.0001), and more frequent in JE (P = 0.03) and those having substantia nigra involvement on MRI (P = 0.03). Dystonia was associated with worse outcome than parkinsonian features only (P = 0.01). Movement disorders are common and severe in JE and are related to typical anatomical involvement.

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.

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.

Cerebrospinal fluid catecholamine levels in Japanese encephalitis patients with movement disorders.

Norepinephrine and dopamine have important role in movement disorders but their role in movement disorders associated with Japanese encephalitis (JE) has not been evaluated. Therefore, in the present study, cerebrospinal fluid (CSF) catecholamine levels and its metabolites in JE patients with movement disorders were compared with those without JE. CSF was collected by lumbar puncture and analyzed by HPLC-ED. Norepinephrine, dopamine and homovanillic acid concentrations were significantly (P<0.005) lower in JE patients compared to control groups. Low levels of catecholamines in JE associated movement disorders compared to idiopathic Parkinson's disease and other extrapyramidal symptoms may be due to severe structural damage to thalamus, basal ganglia and brainstem in JE patients as revealed by MRI findings.

A role for endocannabinoids in viral-induced dyskinetic and convulsive phenomena.

Dyskinesias and seizures are both medically refractory disorders for which cannabinoid-based treatments have shown early promise as primary or adjunctive therapy. Using the Borna disease (BD) virus rat, an animal model of viral encephalopathy with spontaneous hyperkinetic movements and seizure susceptibility, we identified a key role for endocannabinoids in the maintenance of a balanced tone of activity in extrapyramidal and limbic circuits. BD rats showed significant elevations of the endocannabinoid anandamide in subthalamic nucleus, a relay nucleus compromised in hyperkinetic disorders. While direct and indirect cannabinoid agonists had limited motor effects in BD rats, abrupt reductions of endocannabinoid tone by the CB1 antagonist SR141716A (0.3 mg/kg, i.p.) caused seizures characterized by myoclonic jerks time-locked to periodic spike/sharp wave discharges on hippocampal electroencephalography. The general opiate antagonist naloxone (NLX) (1 mg/kg, s.c.), another pharmacologic treatment with potential efficacy in dyskinesias or L-DOPA motor complications, produced similar seizures. No changes in anandamide levels in hippocampus and amygdala were found in convulsing NLX-treated BD rats. In contrast, NLX significantly increased anandamide levels in the same areas of normal uninfected animals, possibly protecting against seizures. Pretreatment with the anandamide transport blocker AM404 (20 mg/kg, i.p.) prevented NLX-induced seizures. These findings are consistent with an anticonvulsant role for endocannabinoids, counteracting aberrant firing produced by convulsive agents, and with a functional or reciprocal relation between opioid and cannabinoid tone with respect to limbic convulsive phenomena.

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.

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.

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.

Elevated GDNF levels following viral vector-mediated gene transfer can increase neuronal death after stroke in rats.

Previous studies have indicated that administration of glial cell line-derived neurotrophic factor (GDNF) counteracts neuronal death after stroke. However, in these studies damage was evaluated at most a few days after the insult. Here, we have explored the long-term consequences of two routes of GDNF delivery to the rat striatum prior to stroke induced by 30 min of middle cerebral artery occlusion (MCAO): striatal transduction with a recombinant lentiviral vector or transduction of the substantia nigra with a recombinant adeno-associated viral vector and subsequent anterograde transport of GDNF to striatum. Despite high GDNF levels, stereological quantification of striatal neuron numbers revealed no protection at 5 or 8 weeks after MCAO. In fact, anterograde GDNF delivery exacerbated neuronal loss. Moreover, supply of GDNF did not alleviate the striatum-related behavioral deficits. Thus, we demonstrate that the actions of GDNF after stroke are more complex than previously believed and that high levels of this factor, which are neuroprotective in models of Parkinson's disease, can increase ischemic damage. Our findings also underscore the need for quantitative assessment of long-term neuronal survival and behavioral changes to evaluate the therapeutic potential of factors such as GDNF.

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.

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.