key: cord-0712698-ysxdy74m authors: Ghosh, Ritwik; Ray, Adrija; Roy, Dipayan; Das, Shambaditya; Dubey, Souvik; Benito-León, Julián title: Parkinsonism with Akinetic Mutism following Osmotic Demyelination Syndrome in a SARS-CoV-2 infected Elderly Diabetic Woman: A Case Report date: 2021-11-11 journal: Neurologia DOI: 10.1016/j.nrl.2021.09.007 sha: df1f9fe56385b91265dd76fead46cb949115e255 doc_id: 712698 cord_uid: ysxdy74m nan The authors declare that they have no conflict of interest. This study was not funded. Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being widely documented. 1 However, de novo movement disorders are scantly reported in COVID-19. 2 Apart from neurological manifestations, SARS-CoV-2 infection can make a previously euglycemic person vulnerable to develop either transient or permanent hyperglycemia. 3, 4 Osmotic demyelination syndrome (ODS), formerly called central pontine myelinolysis, is a serious neurological emergency, which arises from rapid changes in osmotic equilibrium in susceptible neuronal cells, especially oligodendrocytes. 5 However, due to advancement in neuroimaging and our understanding of the pathophysiological processes underlying ODS, more cases of extra-pontine myelinolysis (EPM) are being reported. 3 Among the complications of ODS, parkinsonism has been rarely reported. 6, 7 ODS occurs classically as a complication of the rapid correction of hyponatremia; 3 however, it has been rarely associated with other entities, such as hyperglycemic hyperosmolar state (HHS). 8, 9 Page 4 of 11 J o u r n a l P r e -p r o o f 4 We hereby report a case of an elderly diabetic woman with parkinsonism with akinetic mutism following non-dyselectrolytemic ODS, which was precipitated by COVID-19 induced HHS. An elderly Indian woman aged 65 years with adequately controlled type-2 diabetes mellitus (T2DM) presented to the emergency department with fever, body-ache and dry cough for the last 5 days. She was diagnosed to have SARS-CoV-2 infection in the emergency department. Complete blood cell count revealed neutrophilic leukocytosis with neutrophil to lymphocyte ratio of 3; erythrocyte sedimentation rate, Creactive protein, ferritin, lactate dehydrogenase and hepatic transaminases were raised. Serum electrolytes, blood glucose levels (pre and post-prandial), hemoglobin-A1c, ketones, D-dimer, interleukin-6, cardiac troponins, and thyroid and renal function tests were within normal range. A high-resolution computerized tomography scan of the thorax revealed a severity score of 8/25. She was prescribed inhalational budesonide, oral dexamethasone, doxycycline, ivermectin, antipyretics and subcutaneous basalbolus insulin regimen. On day 4, she had bouts of unprovoked vomiting and became drowsy. Bedside random capillary blood glucose (CBG) measurement revealed high glucose levels (652 mg/dl). Arterial blood gas analysis revealed no dyselectrolytemia or acid-base imbalances. Serum osmolarity was 317 mOsm/kg with normal lactate levels. After 48 hours of stringent management and monitoring, she was still apathetic and responding rarely and incompletely to commands with long latency and became She had no history of addiction and no family history of any neurological disorders. Brain MRI revealed symmetrical hyperintense signals in T2-weighted imaging, T2-FLAIR and DWI over bilateral caudate nucleus and putamen ( Figure 1 ). Clinical-radiological differentials diagnoses that were considered are shown in Table 1 . Eventually, she was diagnosed to be a case of an extrapontine variant of osmotic demyelination syndrome (ODS) due to HHS, which was precipitated by COVID-19, that in turn had been treated with dexamethasone. She was put on levodopa/carbidopa (initially started at 25/6.25 mg 4 times a day and gradually up titrated to 100/25 mg 5 times a day) and pramipexole (1.5 mg/day). After 2 months of follow-up, her features of parkinsonism improved significantly (MDS-UPDRS score of 60 to 20), but with only mild improvement of the features associated with akinetic mutism. Pramipexole was up titrated to 3 mg/day and sertraline (100 mg/day) was added. Throughout her hospital stay, her minimum serum sodium (corrected for hyperglycemia) was 136 mEq/L and maximum was 142 mEq/L. The change in serum sodium was closely monitored and never crossed >5 mEq/L. After another 2 months of follow-up, her mutism also improved significantly and she is currently continuing the same regimen along with drugs and lifestyle modifications for T2DM. We have described a case of parkinsonism with akinetic mutism associated with the worsening of glycemic control in an elderly diabetic woman suffering from SARS-CoV-2 infection. An event-by-event discussion will aid us in dissecting the pathophysiology of this case. Firstly, the loss of glycemic control might either be because of corticosteroid therapy, COVID-19 infection itself, or lack of physical activity. 3, 4 Secondly, the ODS results from maladaptive stress due to rapid change in the osmotic milieu within the neurons, possibly due to disruption of blood-brain barrier, exposure of glial cells to activated complements and cytokines, which in combination eventually lead to axonal shear injury, cellular energy depletion and apoptosis. 5 However, some researchers attribute this to an osmotic disequilibrium-related endothelial damage and the subsequent release of inflammatory mediators from the injured endothelial cells. 8, 10 Rapidly developing HHS is a rare, although documented, risk factor of ODS. 8, 9 It is highly plausible that in our patient, HHS developed rapidly enough that oligodendrocytes could not adapt. Interestingly, all the previously mentioned pathogenetic mechanisms (i.e. endothelial damage, disruption of bloodbrain barrier, cytokine-mediated cellular injury, etc.) leading to ODS can also occur in COVID-19 itself, 11, 12 and this raises the question whether the SARS-CoV-2 infection itself is capable of causing ODS. However, we feel that in our patient was due to the rapid surge in plasma glucose and thereby plasma osmolarity. Thirdly, what caused parkinsonism with akinetic mutism? There are three possibilities. The uncontrolled hyperglycemic state is established as a cause of potentially reversible de novo movement disorders (diabetic striatopathy). 13, 14 Besides, the EPM variant of ODS is particularly known for its predilection to give rise to de novo movement disorders because of the involvement of the crucial striato-thalamo-cortical networks. 6 Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic De Novo Movement Disorders and COVID-19: Exploring the Interface Choreo-ballistic movements heralding COVID-19 induced diabetic ketoacidosis COVID-19: the endocrine opportunity in a pandemic Osmotic demyelination syndrome Osmotic Demyelination Syndrome With Evolving Movement Disorders Movement disorders and the osmotic demyelination syndrome Osmotic demyelination syndrome as the initial manifestation of a hyperosmolar hyperglycemic state Osmotic demyelination syndrome due to hyperosmolar hyperglycemia Osmotic demyelination syndrome: central pontine myelinolysis and extrapontine myelinolysis Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response During SARS-CoV-2 Infection Endothelial cell infection and endotheliitis in COVID-19 Diabetic striatopathy": clinical presentations, controversy, pathogenesis, treatments, and outcomes Hemifacial Spasm as the Presenting Manifestation of Type 3c Autoimmune limbic encephalitis related to SARS-CoV-2 infection: Case-report and review of the literature Hepatic functions including albumin, prothrombin time, and international normalized ratio were normal. There was only mild elevation of levels of transaminase No myoclonus, tremor and asterixis were noted Hypoxemic encephalopathy 1. Patient was on continuous monitoring and never had an episode of hypoxemia/hypoxia. 2. No myoclonus Wernicke's encephalopathy (WE) Hyperacute course