Functional movement disorders during the COVID-19 pandemic

Functional movement disorders (FMDs) are a heterogenous group of movement abnormalities that greatly affect the quality of life of patients. They usually manifest as a result of underlying psychological or psychiatric illnesses without any known structural or neurochemical diseases. Various neurological disorders such as encephalitis, stroke, demyelination, seizures, and neuropathy have been reported by otherwise healthy individuals during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we describe the case of a 27-year-old woman who presented to our outpatient department with episodes of deviation of angle of mouth with variability and distractibility. Following thorough clinical evaluation and appropriate investigation, the underlying etiology was identified as FMD secondary to the restrictions imposed during the COVID-19 pandemic to contain the transmission of the virus. The lockdown, isolation, financial strain, and other pandemic-related issues are stressors that may contribute to psychogenic disorders in people.Copyright © 2021 Annals of Movement Disorders Published by Wolters Kluwer - Medknow.

Coronavirus in patient with positive PCR test in cerebrospinal fluid led to generalized tonic-clonic seizure without brain lesion: a case report

SARS-CoV-2 which first was observed in Wuhan region, China in December 2019 is affected many organs, such as central nervous system. We describe a case of a 57-year-old male patient, in hospital with the loss of consciousness, in the form of lack of verbal and visual communication. He got a seizure attack for about 3 minutes in the form of generalized tonic-clonic seizure (GTS) and admitted to the neurological department and was intubated. Since, the patient was not aware, awake, did not obey, corneal reflexes test was positive and his pupils were isochoric and reactive therefore, the primary diagnosis was cerebrovascular accident (CVA). On the second day after admission, although the brain computed tomography (CT) did not show brain lesion, but chest X-ray (CXR) revealed lung involvement. In addition, on third day the RT-PCR test for coronavirus RNA in and the cerebrospinal fluid and nasopharyngeal swap done and the result was positive for both of them. Therefore, treatment for the covid-19 was started. Result(s): Since, the treatment for the covid-19 was started with Atazanavir, Clindamycin and ceftriaxone, ten days after hospitalization, the lung involvement and general condition of patient got better and after two weeks he was released from the hospital. Conclusion(s): GTS should be considered as a neurological outcome of COVID-19 and medications against the coronavirus, such as Atazanavir, Clindamycin and ceftriaxone can recover the neurological deficits in these patients.Copyright© 2020, TMU Press.

Acute encephalitis following COVID-19 vaccines: A case series

Case report Background: Neurological adverse effects (NAE) as headache and dizziness are commonly reported with COVID-19 vaccines but are transient and self-limited. However, few serious NAE have been recently described which can be fatal. Here we report two rare cases of encephalitis related to COVID-19vaccination BNT162b2 (Pfizer) and mRNA-1273 (Moderna) and the inherent challenges in their diagnosis. Method(s): We report two cases of acute encephalitis notified to the department of pharmacovigilance in the University Hospital of Monastir Results: Case n'1: Three weeks after receiving her first dose of mRNA-1273, a 35-year- old female, with a medical history of hypothyroidism and eczema was admitted to the intensive care unit as she had confusion and a febrile tonic-clonic seizure complicated with a status epilepticus and dysautonomia. CSF investigations were nonspecific, and the MRI head did not detect any abnormality. Common causes were excluded by an extensive workup (neoplastic, neuro-vascular, autoimmune and infectious causes). She received cefotaxime and acyclovir without any recovery. However, a spectacular recovery was noticed when receiving methylprednisolone. Case n'2: Three days after receiving her first dose of BNT162b2, a-40- year- old female, with a medical history of rheumatoid arthritis was admitted to the medical care unit as she had experienced a three-day history of headache, memory disturbance, severe cognitive disorders and 4 febrile tonic-clonic seizures. MRI head showed signs of bitemporal encephalitis and CSF investigations was with no findings. Extensive laboratory studies ran out alternative causes as neoplastic, autoimmune and infectious diseases. A twenty-one- day acyclovir regimen was administrated with no recovery. As the cognitive deficit is getting more severe, she got intravenous immunoglobulin therapy with a spectacular improvement. Conclusion(s): Based on the Naranjo Algorithm, this adverse NAR can be possibly (score = 6) induced by COVID-19 vaccines. The dramatic improvement after receiving either corticoids or immunoglobulin therapy supports an immune-mediated mechanism behind this acute presentation. Cases of acute encephalitis secondary to H1N1 influenza and poliomyelitis vaccines have been previously reported but those related to COVID-19 vaccines are still not yet elucidated due to the unproven causality. Further prospective studies are needed to evaluate the causal association between vaccine and NAE occurring vaccination.

An unusually fulminant case of encephalomyelitis in an 80 year old

Background: There have been reports of demyelinating syndromes in association with COVID-19 and to a much lesser extent COVID 19 vaccines. The association between demyelination and vaccines, in general, remains controversial. We review a presentation of fulminant demyelination, and discuss antecedent COVID-19 vaccination, the formulation of a broader differential diagnosis and ultimately the pathologic diagnosis. Case presentation: An 80-year-old woman presented with seizure, encephalopathy, quadriparesis and ultimately expired. She received a SARS-CoV-2 vaccine one day prior. Imaging revealed contrast enhancing cerebral lesions, longitudinally extensive transverse myelitis. CSF was markedly inflammatory. Pathologic examination of the CNS lesions revealed demyelination and inflammation beyond white matter, not restricted to a perivenular distribution. Conclusion(s): This case depicts a seemingly fulminant course of a diffuse demyelinating syndrome characterized clinicopathologically as Marburg's variant of multiple sclerosis. There are several unique aspects of this case including the extremely rapid course, the unusual evolution of CSF abnormalities, with hypoglycorrhachia and markedly elevated protein. The proximity to vaccination is a pertinent association to document, though we cannot unequivocally prove causation.Copyright © 2022 The Authors

Hemiconvulsion-Hemiplegia-Epilepsy Syndrome in the Setting of COVID-19 Infection and Multisystem Inflammatory Syndrome in Children

Objective: To present a case of Hemiconvulsion-Hemplegia-Epilepsy (HHE) Syndrome in a child with COVID-19 infection and Multisystem Inflammatory Syndrome in Children (MIS-C). Background: HHE Syndrome is a rare pediatric epilepsy syndrome that presents with prolonged unilateral convulsive status epilepticus in the setting of fever, followed by hemiparesis, unilateral hemispheric swelling and atrophy, and the development of epilepsy. Though it was first described over six decades ago, the pathophysiology is still poorly understood with multiple factors contributing, including hyperthermia, inflammation, and cytotoxic edema from prolonged ictal activity. Prognosis is variable, from the resolution of hemiplegia and seizures to permanent hemiparesis and refractory epilepsy. Design/Methods: This is a case report based on a chart review. Results: The patient is a 2-year-old boy with a history of one prior complex febrile seizure who presented with greater than one hour of convulsive status epilepticus in the setting of fever. The patient had a generalized tonic-clonic seizure with more prominent convulsions on the right side. The patient required intubation and was initially given multiple anti-seizure loads though continued to have persistent electrographic and electroclinical seizures. EEG showed lefthemispheric high amplitude spike/polyspike and wave discharges. The patient required continuous midazolam infusion with eventual control of seizures on levetiracetam, phenobarbital, and clobazam. The examination was notable for persistent right-sided hemiparesis with gradual improvement. MRI brain without contrast revealed T2 signal abnormality and restricted diffusion diffusely throughout the left cerebral hemisphere. Infectious workup was significant for positive COVID-19 PCR and elevated inflammatory markers, consistent with MIS-C. Conclusions: Our patient had prolonged focal convulsive status epilepticus in the setting of acute febrile illness secondary to COVID-19 and MIS-C leading to hemiparesis and diffuse left cerebral hemisphere edema on MRI brain consistent with HHE syndrome. More research is needed to elucidate further HHE syndrome's pathophysiology and assess long-term outcomes in patients with HHE syndrome.

Hypertension Secondary to COVID-19 Leading to Posterior Reversible Encephalopathy Syndrome in a 13-year-old Male

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiological condition defined by white matter vasogenic oedema predominantly affecting the posterior occipital and parietal lobes. A 13-year-old male presented with complaints of fever for 4 days.Upon evaluation, he turned out positive for COVID-19 with a Computed Tomography (CT) severity score of 5/25. Three days post admission (day 7 of illness), patient developed sudden onset of painless, diminution of vision in both eyes followed by two episodes of generalised tonic clonic seizures. Examination revealed a blood pressure of 180/110 mmHg. Characteristic Magnetic Resonance Imaging (MRI) findings led to a diagnosis of PRES. Patient was treated with antiepileptics, antihypertensives and intravenous mannitol and made a complete recovery. Early identification, treatment of symptomatology and correction of the underlying cause are all key aspects of management.

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES) IN MILD AND SEVERE COVID-19

As the COVID-19 pandemic progresses neurological complications are increasingly being reported. Posterior reversible encephalopathic syndrome (PRES) is a clinico-radiological syndrome characterised by headache, visual loss, encephalopathy and seizures, and the development of vasogenic white matter lesions in a classically parieto-occipital distribution. The pathophysiology of PRES is incompletely understood, but both hyperperfusion secondary to hypertension, and endothelial dysfunction leading to vasogenic oedema have been implicated. Here we present a case series of 2 hospitalised COVID-19 patients with markedly different disease severity, both of whom developed PRES. Patient 1 presented with confusion and headache without significant systemic features, on a background of known hypertension. Patient 1 had a single generalised seizure and was managed with levetiracetam and antihypertensives, and showed complete clinical recovery. In contrast, patient 2 presented with respiratory distress, metabolic disturbance and encephalopathy requiring critical care admission. Patient 2 had a protracted admission, developing marked visual disturbance and generalised seizures requiring multiple agents. In both cases initial CT/MRI showed characteristic posterior PRES-like leukoencephalopathy with resolution on follow-up imaging, and CSF biochemistry, cytology and virology were normal. This case series highlights the potential for neurological complications in COVID-19 patients across the spectrum of disease severity.

New onset limbic encephalitis and COVID-19 vaccine: a case report

Background: Autoimmune limbic encephalitis (ALE) is an inflammatory disease involving the medial temporal lobes. It is characterized by subacute onset of short-term memory deficits, seizures and psychiatric disorders. Few new cases of ALE associated both with SARS-CoV2 infection and COVID-19 vaccine have recently been described. Case presentation: A 56-year-old woman was admitted to emergency department for persistent fever and acute onset of confusion few days apart the first dose of BNT162b2 COVID-19 vaccine. Neurological examination revealed confusion and short-term memory loss. Blood test showed only leukopenia and mild increase of the PCR. The patient underwent brain CT-scan which excluded organic lesion for the cognitive deficit. During the hospitalization the patient presented tonic clonic seizures and postictal state therefore an EEG was performed and revealed epileptiform abnormalities in the temporal lobes. Since the hypothesis of encephalitis brain MRI and lombar puncture for cerebral spinal fluid (CSF) analysis were performed with evidence of T2 hyperintensity in temporal lobes and normal values of CSF. Despite steroid and antiepileptic therapy with Carbamazepine, Valproate and Perampanel, several epileptic relapses occurred and there was no improvement of neurological manifestation. The patient was finally discharged with need of home care Conclusions: New onset ALE following COVID-19 vaccine or infection has rarely been described. Clinicians should monitor neurological symptoms to ensure appropriate therapy to maximize the likelihood of good outcome.

Blinatumomab and inotuzumab ozogamicin for acute lymphoblastic leukaemia: data from the South East Scotland Cancer Network

Current therapy for adults with B-cell acute lymphoblastic leukaemia (B-ALL) remains suboptimal, despite good initial remission rates. Adults with relapsed or refractory B-ALL (R/R B-ALL) represent a challenge with historically poor outcome;the introduction of targeted agents has expanded options but there is no consensus management. Blinatumomab is a bispecific T-cell engager antibody construct against CD19 (Scottish Medicine consortium, SMC, approval February 2020);inotuzumab is a monoclonal anti-CD22 antibody conjugated to calicheamicin (SMC approval May 2018). Trial data have shown both agents improved remission rates and survival when compared with standard chemotherapy with manageable toxicity profiles, although adverse events including neurological toxicity and cytokine release syndrome (CRS) have been reported. We describe the experience of blinatumomab and inotuzumab in a BCSH level three unit from February 2017 to August 2021. Eleven patients-six male, five female, mean age 41.5 years (range 22-55) received a monoclonal antibody;blinatumomab ( n = 8) and inotuzumab ( n = 3). Ten had B-ALL and one had mixed lineage leukaemia (MLL). All patients were Philadelphia negative. Cytogenetic abnormalities were present in four cases-Inv(20), trisomy 21 (patient with Down syndrome), tetraploidy with isochromosome 17q and one with a complex karyotype. Further molecular information was available for nine cases, and all were negative for TCF3-PBX1 t(1;19), ETV6-RUNX1 t(12;21) and KMT2A rearrangements (including the case with MLL). Four patients received blinatumomab due to refractory BALL. Two (50%) went on to receive an allogeneic transplant in CR1 (one MRD negative and the other MRD below limit of quantification). Both patients were able to maintain a performance status of 0-1 pretransplant. One patient (25%) died due to SARS-COV-2 infection and the fourth patient's care was lost to follow-up. Four patients received blinatumomab due to relapsed BALL, two had undergone allogeneic transplant in CR1. Two patients (50%) died of progressive B-ALL. One patient is currently on UKALL 2011 regimen B maintenance B2 (comorbidities preclude allogeneic transplant), the other patient remains in molecular remission having failed lymphocyte collection for chimeric antigen (CAR) T-cell therapy. Three patients received inotuzumab for relapsed B-ALL. Two (66%) had a previous allogeneic transplant in CR1-one of whom went on to receive donor lymphocyte infusion (DLI) postinotuzumab while the other patient went on to have a second allogeneic transplant. The third patient relapsed on maintenance chemotherapy and has been referred for allogeneic transplant. Infective episodes occurred in 45% (all received blinatumomab) including one death from SARS-COV-2 pneumonitis. Following blinatumomab CRS and neurotoxicity (tonic-clonic seizures) occurred (both n = 1). No significant toxicities were observed in the three patients who received inotuzumab, although this likely reflects small patient numbers rather than a true difference between the two agents. Despite improved responses in R/R B-ALL with these therapies as single agents for the majority they do not offer cure. While toxicity was recorded it did not negatively impact PS. CAR T-cell therapy has demonstrated high initial remission rates in heavily treated B-ALL patients, including previous targeted therapy. Optimal sequencing of therapies remains to be defined alongside depth of response and duration of measurement.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion of the corpus callosum in childhood: a single-center experience

Background/aim: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a rare clinicoradiological syndrome that typically presents with central nervous system symptoms such as loss of consciousness, seizure, headache, and ophthalmoparesis. Materials and methods: Here, we highlight the characteristics of this syndrome together with the clinical and MRI findings of 6 pediatric patients with MERS. Results: Between January 2017 and October 2020, 6 patients with MERS (3 boys and 3 girls) presented to our center. The mean age was 122 ± 54.6 (min-max: 44-180) months. None of the patients had a chronic disease. In our study, infectious agents were detected in 4 patients (66.6%), while noninfectious causes (one seizure and the other hyponatremia) were detected in two patients. All of our cases were discharged without any sequelae after an average of 12.1 ± 7 (min–max: 4–20) days of hospitalization. In 1 patient (case 6), control MRI could not be performed, and the radiological recovery of our other patients was shown to be between 14 days and 2 months. Conclusion: MERS is an acute encephalopathy with good prognosis and should be considered by neurologists in differential diagnosis due to its variable clinical presentation and specific MRI findings.

Seizure, abdominal pain, and urine pink in an adolescent female-what's the link?

Case Report A 17 year-old female with history of depression was transferred to the pediatric intensive care unit (PICU) from an emergency department (ED) for first time seizure and subsequent encephalopathy after five days of severe, diffuse abdominal pain and vomiting. The night prior to admission, she complained of lightheadedness and then had a witnessed generalized tonic-clonic seizure lasting 45 seconds. She initially returned to her baseline but then had three additional seizures requiring ED evaluation. She received intravenous doses of lorazepam and levetiracetam that aborted the clinical seizures. She remained encephalopathic and was orotracheally intubated for airway protection. Family denied known ingestions but reported she did vape nicotine. Urine drug screen was positive for benzodiazepines, consistent with seizure management. Cerebrospinal fluid analysis was unrevealing. Urinalysis showed moderate ketones and trace blood. Urine pregnancy test and nasopharyngeal SARS-CoV-2 polymerase chain reaction were negative. Head computerized tomography scan showed no intracranial pathology. On arrival to the PICU, the patient was afebrile, tachycardic, and hypertensive to 171/118 mmHg. She was somnolent on arrival but aroused to sternal rub without focal neurologic deficit. She presented with a Foley catheter that drained pinkorange urine. A nicardipine infusion was started given concern for the development of posterior reversible encephalopathy syndrome (PRES). Thyroid function tests were consistent with euthyroid sick syndrome. BioFire meningitis panel, plasma SARS-CoV-2 IgG, and toxicologic evaluation were all negative. Electrocardiogram showed sinus tachycardia. Magnetic resonance imaging of the brain revealed cortical and subcortical areas of diffusion restriction consistent with PRES. Ultimately, a random urine porphobilinogen and a 24-hour measurement of urine porphyrins collected on hospital day 1 were both markedly elevated. A diagnosis of Acute Intermittent Porphyria (AIP) was made. A gastrointestinal porphyria specialist was consulted and recommended monthly outpatient injections of givosiran upon hospital discharge. Discussion This case illustrates the importance of considering AIP in the differential diagnosis of new onset seizure or encephalopathy associated with hypertension, tachycardia, and abdominal pain in an adolescent. This case also adds to a small number of cases associating AIP with PRES. AIP is often viewed as an adult disease because it typically presents in the third or fourth decade of life. Timely recognition of AIP in the pediatric setting is critical to preventing delays in diagnosis, treatment, and patient education on triggers of acute attacks. AIP attacks are treated with dextrose and hemin infusions to reduce production of porphyrin precursors. Prophylactic treatment of AIP now includes givosiran, an interfering mRNA that reduces levels of intermediates in heme synthesis that are neurotoxic when elevated.

The efficacy equivalence of generic levetiracetam in West China: A perspective study

Purpose: During the COVID-19 pandemic, the supply chain of the anti-seizure medication has been challenged. On the other side, the “4+7” drug procurement reform launching in China also force the promotion of generics. This study is aimed to investigate the attitude and efficacy of the antiseizure drug levetiracetam and its genric production in Chinese people with epilepsy. Method: The study is conducting in the clinic in 10 epilepsy centers in Westchina.The inclusion criteria are 1) diagnosed with epilepsy for more than 3 months;2) has started standard levetiracetam treatment for more than 3 months during the course;3) informed consent was obtained. Participates were consecutively recruited. The data is collected through fact-to-face interview and self-report surveys. Result: This ongoing study has currently enrolled 40 people with epilepsy. The average age is 24.3 yrs, the median age is 25.0 yrs. 72.5% of them was female. Twenty-eight of them were diagnosed with focal onset seizure, four has generalized onset seizure. Of 39 patients who are currently using levetiracetam, 29 (74.3%) were using the brand drug. 30% of patients had switch the brand without discussion with doctors. Mainly because of the unstabled supply and expenses. In 3 cases, participates complains the difference in efficacy of the treatment. Only 40% of the participates agree that the efficacy and safety of generic drugs are equal to the brand product. Conclusions: From the preliminary results, there are a large proportion of people with epilepsy has switched the brand of their levetiracetam drug. While a limited number of cases showed differences in efficacy and safety, most of the patients doubt the equivalence.