key: cord-0735676-olmnsew6 authors: Yaranagula, Sai Deepak; Koduri, Venkata Krishna Chaitanya title: DimachkieSpectrum of Acute Neuropathy Associated with Covid-19: Clinical and electrophysiological study of 13 patients from a single center date: 2021-07-29 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.07.066 sha: aeb60b09b321e1b04c4b7758252644d10d798a02 doc_id: 735676 cord_uid: olmnsew6 OBJECTIVES: To analyze clinical and nerve conduction patterns in patients with acute neuropathy, preceded by or concomitantly having Covid-19 disease (Acute Neuropathy Associated with Covid-19 or ANAC 19). METHODS: Retrospective analysis of clinical details, laboratory evaluation and electrophysiological parameters in patients with ANAC 19was done. This data was compared with non Covid GBS described in literature and also with patients of acute neuropathy without Covid 19 who had presented to our center during the period of study. RESULTS: Records of thirteen patients with ANAC 19were reviewed. Most patients clinically had paraparesis, and electrophysiologically showed demyelinating neuropathy. Peroneal and Sural nerves were the most frequently abnormal motor and sensory nerves respectively. A proportion of patients showed a peroneal velocity sparing pattern. Higher incidence of paraparesis and encephalopathy differentiated ANAC 19from non Covid GBS. CONCLUSIONS: ANAC 19has a comparable electrophysiological profile to non Covid GBS. However, it has a distinct clinical presentation. Acute neuropathy in Covid-19 disease is a well-recognized association. Acute inflammatory demyelinating polyneuropathy (AIDP), Acute motor sensory axonal neuropathy (AMSAN)and other varieties of Covid-19 associated Guillain-Barre syndrome (GBS)have been summarized in systematic reviews (Abu-Rumeileh et al., 2021; Sriwastava et al., 2021) . Though previous authors have described electrophysiological characteristics of Covid 19 related neuropathy, they are limited to specific neuropathy types such as AIDP (Uncini et al, 2021) or critical illness neuropathy (Frithiof et al, 2021) . Through this retrospective case series, we aim to analyze clinical and nerve conduction patterns, in patients with a broad spectrum of acute neuropathy, preceded by or concomitantly having Covid-19 disease ( ANAC 19) . We then apply the GBS diagnostic criteria at the patient level and single nerve level to provide a comprehensive electrophysiological insight into ANAC 19. Each NCS was done as the last study of the day following which the lab was fumigated. Records of bilateral median (motor including F waves, and sensory), ulnar (motor including F waves, and sensory), peroneal (motor including F waves) and sural (sensory) NCS were reviewed. Sensory NCS was antidromic in sural, and antidromic/orthodromic in median and ulnar. One patient could not undergo left ulnar NCS due to technical reasons. Normative data (except for antidromic upper limb sensory amplitudes) was derived from Gupta et al (Gupta et al., 1994) and Taly et al (Taly et al., 1991) . Normative sensory amplitudes for antidromic median (13 microvolts) and antidromic ulnar (9 microvolts) were derived from Chen et al (Chen et al., 2016) . The normative NCS parametersused in the study are tabulated in table 1. Hadden criteria (Hadden et al., 1998) were applied to classify the NCS as demyelinating, axonal or others. Umapathi criteria (Umapathi et al., 2019) were applied to classify as definite, probable or possible Guillain-Barre syndrome (GBS). Clinical presentation, imaging, and Cerebro-spinal fluid (CSF) analysis when available were evaluated in addition. Clinical presentation and laboratory evaluation details of thirteen patients were analyzed. Twelve patients were confirmed Covid-19 with RT PCR/rapid antigen test, while one patient was probable Covid-19. Four patients were female and nine were male. Mean age of the cohort was 65.54±8.6 years( Table 2) . Fever (n=9), dyspnea (n=7) and cough (n=5) were the most common presenting manifestations of Covid-19 in the cohort. Risk factor assessment for severe Covid 19 disease revealed diabetes in eleven patients, hypertension in eight, CAD in two, CKD in one and obesity in two patients. Following the onset of non-neurological Covid 19 features, neuropathic symptoms started in the first week of illness in three patients, in the second week in one patient, in the third week in four patients, in the fourth week in three patients, and in the second month in one. One patient had onset beyond two months of Covid 19. This patient experienced progressive worsening of pulmonary symptoms coincident with the onset of neurological symptoms, probably suggesting reinfection. Eleven patients were diabetic at presentation. Duration of diabetes was available in the records of two patients. One of these was diabetic for five years and another for 1 and ½ months prior to the onset of neuropathy. Diabetes duration of another six patients was reviewed through telephonic enquiry. Of these, one patient denied diabetes prior to onset of Covid. Four patients were diabetic for 20 years or more and one patient for 1 and ½ years. The duration of diabetes for three patients could not be accessed. Sensory NCS parameters were classified as absent SNAPs, normal SNAPs or reduced amplitude (but not absent) SNAPs. Details of the sensory NCS are summarized in Table 5 . Majority of the patients (n=9) were categorized as probable GBS on applying Umapathi criteria (Umapathi et al., 2019) . Both the patients with axonopathy on NCS belonged to this category. Two patients with probable GBS had CSF analysis done and both showed albumino-cytological dissociation consistent with inflammatory radiculo-neuropathy. Seven patients with probable GBS did not having CSF analysis. However, among these seven, structural pathology of Brain and spine was ruled out in two patients with an MRI. In another two patients, MRI Brain alone was done which was again non-contributory. Three patients with probable GBS had neither MRI nor CSF analysis. However, all the three had limb weakness with hyporeflexia clinically consistent with radiculoneuropathy. Other laboratory evaluation details of the patients were reviewed. Serum globulin (n=13), a marker for paraproteinemias (Rison &Beydoun, 2016) , was normal in all patients except one, who had a transient serum globulin elevation. Hypercalcemia is another indication to screen for M protein (Cook& MacDonald, 2007) . Corrected serum calcium (n=11) was normal in all tested patients. Urine bence jones protein was done in one patient and was negative. Urine porphobilinogen done in three patients was negative. Vitamin B12 levels (n=10) were high in eight (probably due to Vitamin B12 supplementation prior to testing) and normal in two patients. Among patients with encephalopathy (n=4), two patients had definite GBS while the remaining two had probable GBS. Three patients had quadriparesis and one had paraparesis. MRI brain was done in all four patients and was non-contributory. Two patients had CSF analysis out of which one had albumino-cytological dissociation. Two patients were seen in OPD. Their clinical course after initial assessment was therefore unclear. Modified rankin scale (Brodericket al, 2017) in eight inpatients and MRC sum score (Turan et al, 2020 ) in three inpatients is described (Supplementary table 3) . Out of the eleven inpatients in the cohort, six were static, three improved and two worsened during the hospital stay. F wave abnormalities were most sensitive NCS parameter similar to non covid polyneuropathies (Sathya et al., 2017) . Absent F waves were more frequently seen than prolonged F latencies. Absent F waves as a significant feature of Covid-19 associated AIDP has been previously noted Therefore, peroneal velocity sparing may be a better marker for demyelinating neuropathy and definitely warrants further evaluation in a larger cohort of patients. Presence of diabetes in most of the Covid patients in our study may have confounded some of the electrophysiological findings. Subclinical NCS abnormalities are relatively common in diabetic patients (Akbar et al, 2000) . Therefore, the possibility that the NCS abnormalities noted in our patients were in fact caused by pre-existing diabetic neuropathy cannot be ruled out. However, the pattern of acute neurological symptoms in our cohort is unlikely to have been caused by diabetes. Also, axonopathy is more common than demyelinating pattern in diabetes (Bansal et al, 2006) , which is contrary to the findings in our cohort which shows a predominant demyelinating neuropathy. 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Crit Care A Simplified, Graded, Electrodiagnostic Criterion for Guillain-Barré Syndrome That Incorporates Sensory Nerve Conduction Studies. Sci Rep We thank our neurology technicians, Ms. Thriveni. V and Mr. Eswar Reddy for performing the NCS on the patients. We are also grateful to the critical care team and intensivists for their care of the sick patients during the NCS. Dr S.D.Y was involved in the conception of the study, acquisition, analysis and interpretation of data, and drafting the manuscript. Dr V.K.C.K was involved in acquisition, analysis and interpretation of data, and drafting the manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that there were no sources of funding for this study. Given the retrospective nature of the study and the fact that it does not provide any personal information of the patients, no authorization to an Ethics Committee was asked.