Chronic inflammatory demyelinating polyradiculoneuropathy-associated tremor: Phenotype and pathogenesis.

BACKGROUND AND PURPOSE: Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is underrecognized, and the pathophysiology remains incompletely understood. This study evaluated tremor in CIDP and tested the hypothesis, established in other demyelinating neuropathies, that tremor occurs due to mistimed peripheral inputs affecting central motor processing. Additionally, the tremor stability index (TSI) was calculated with the hypothesis that CIDP-related tremor is more variable than other tremor disorders. METHODS: Consecutive patients with typical CIDP were prospectively recruited from neuromuscular clinics. Alternative causes of neuropathy and tremor were excluded. Cross-sectional clinical assessment and extensive tremor study recordings were undertaken. Pearson correlation coefficient was used to compare nerve conduction studies and tremor characteristics, and t-test was used for comparisons between groups. RESULTS: Twenty-four patients with CIDP were included. Upper limb postural and action tremor was present in 66% and was mild according to the Essential Tremor Rating Assessment Scale. Tremor did not significantly impact disability. Surface electromyography (EMG) found high-frequency spectral peaks in deltoid (13.73 ± 0.66 Hz), biceps brachii (11.82 ± 0.91 Hz), and extensor carpi radialis (11.87 ± 0.91 Hz) muscles, with lower peaks in abductor pollicis brevis EMG (6.07 ± 0.45 Hz) and index finger accelerometry (6.53 ± 0.42 Hz). Tremor was unchanged by weight loading but correlated with ulnar nerve F-wave latency and median nerve sensory amplitude. TSI (2.3 ± 0.1) was significantly higher than essential tremor. CONCLUSIONS: Postural tremor is a common feature in CIDP. Tremor was unaffected by weight loading, typical of centrally generated tremors, although there was a correlation with peripheral nerve abnormalities. The high beat-to-beat variability on TSI and gradation of peak frequencies further suggest a complex pathophysiology. These findings may assist clinicians with the diagnosis of neuropathic tremor.

Demyelinating Diseases: From Molecular Mechanisms to Therapeutic Strategies.

Demyelinating diseases are a group of pathologies characterized by the alteration of myelin-that is, the coating that wraps around most of the nerve fibres of the central and peripheral nervous system, whose goal is the improvement of nerve conduction and the preservation of energy spent during action potential propagation [...].

Electrophysiological assessment in patients with COVID-19-related peripheral neuropathies and myopathies: a systematic review.

Neurological manifestations associated with Coronavirus Disease-2019 (COVID-19) are commonly reported, but patients were not referred to perform the electrophysiological assessment. We aimed to review the existing literature on clinical studies on COVID-19 peripheral neuropathy to correlate patients' symptoms and characteristics with nerve conduction studies/electromyography (NCS/EMG) outcomes. This protocol is registered in the Open Science Framework (https://www.doi.org/10.17605/OSF.IO/ZF4PK). The systematic search included PubMed, ScienceDirect, and Google Scholar, for articles published from December 2019 to March 2022. A total of 727 articles were collected, and according to our inclusion and exclusion criteria, only 6 articles were included. Of 195 participants, only 175 underwent NCS/EMG assessment. Of these, 44 participants (25.1%) had abnormal EMG, 54 participants (30.8%) had abnormal motor NCS, and only 7 participants (4%) had abnormal sensory NCS. All cases presented with myopathy, while a limited number of cases presented with polyneuropathy. According to motor NCS and EMG, the most affected nerves were the tibial and peroneal in the lower extremities and the ulnar nerve in the upper extremities. Interestingly, the median nerve was reported to be associated with the severity and the rate of motor recovery of patients with COVID-19. COVID-19 generates a demyelinating motor neuropathy and myopathy. Clinicians are encouraged to refer patients with COVID-19 presenting with neurological symptoms to be assessed by electrophysiological methods to objectively determine the nature of their symptoms, follow their prognosis, and plan their rehabilitation.

Post COVID-19 Guillain-Barre syndrome presents as sensory dominant neuropathy with reversible conduction failure.

Guillain-Barré syndrome (GBS) has several clinical variants. The sensory presentations of GBS are atypical but well-recognized. We report a patient who presented with predominantly sensory symptoms associated with reversible conduction failure (RCF). RCF is a well-defined neurophysiological abnormality noted mainly in axonal GBS and may be misinterpreted as evidence of demyelination. A 25-year-old woman presented 2 weeks after a coronavirus 2019 infection with acute sensory symptoms, distal allodynia, mild weakness, and mild hyporeflexia in her upper limbs. A nerve conduction study (NCS) showed delayed motor distal latencies, and lumbar puncture confirmed cytoalbuminologic dissociation. After excluding other etiologies, she was diagnosed with GBS, treated with an IV immunoglobulin course, and showed remarkable recovery. Results of a repeat NCS were consistent with RCF and confirmed the presence of axonal GBS. Increased awareness of sensory GBS and RCF is expected to improve the diagnosis and management of atypical GBS presentations.

Electroneurological changes in peripheral nerves in patients post-COVID.

Various neurological manifestations are observed in about 36.4% of patients infected with SARS-CoV-2 and post-COVID neuropathy is one of them. There is lack of studies describing neurophysiological abnormalities in peripheral nerves in case of patients who had SARS-CoV-2 infection. The aim of this study was to analyze the changes in peripheral nervous system in case of COVID-19 survivors. In the presented study, 45 COVID-19 survivors who had nerve conduction study (NCS) were involved. Results were compared with control group consisting of healthy patients who had nerve conduction study before the COVID-19 pandemic. In our study group, neurophysiological abnormalities were present in the case of both sensory and motor nerve fibers. The most significant reduction of NCS parameters was observed in the case of sensory action potential amplitude of sural nerve. Moreover, that correlation was the most significant in the case of amplitude and conduction velocity in sensory and motor neuron fibers both in arms and legs. Those abnormalities were observed even 6 mo after COVID-19. Further investigation needs to be done regarding the polyneuropathies associated with human coronaviruses, and we should answer the question whether the virus directly damages peripheral nerves or factors mediating inflammatory response are responsible for the neural damage.NEW & NOTEWORTHY Various neurological manifestations are observed in about 36.4% of patients infected with SARS-CoV-2 and post-COVID neuropathy is one of them. There is lack of studies describing neurophysiological abnormalities in peripheral nerves in case of patients who had SARS-CoV-2 infection. The aim of this study was to analyze changes in peripheral nervous system in case of COVID-19 survivors.

Acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination: A report of three cases and review of the literature.

Small fiber neuropathy usually presents with gradual and progressive chronic length-dependent pain. Acute small fiber neuropathy is rarely reported. Three patients with acute onset neuropathic pain after Oxford-AstraZeneca ChAdOx1-S vaccination are described. Two patients were identified at the Oxford University NHS Foundation Trust, Oxford, UK and one patient in Red de Salud UC Christus, Santiago, Chile. All patients underwent a clinical assessment that included a detailed neurological examination, laboratory investigations, nerve conduction studies, thermal threshold testing, and skin biopsy for intra-epidermal nerve fiber density. Patients seen in Oxford underwent MRI of the brain and spinal cord. Cerebrospinal analysis was not performed. Neuropathic symptoms (burning pain, dysaesthesias) developed in the hands and feet within 2 weeks of vaccination. On clinical examination, there was pinprick and thermal hyposensitivity in the area of neuropathic pain. Laboratory investigation, nerve conduction tests, sympathetic skin responses, and MRI showed no relevant abnormalities. Thermal thresholds were abnormal and intra-epidermal nerve fiber density in the lower leg was reduced. In two cases symptoms persist after several months. Three cases of definite acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination are described. At follow up, neuropathic pain was present in two of the patients.

Visual evoked potential and nerve conduction study findings in patients recovered from COVID-19.

OBJECTIVE: COVID-19 infection is associated with peripheral neuropathy. However, subclinical neurological involvement may occur anytime, and diagnostic methods that reveal this subclinical involvement are not well established. We aimed to assess the subclinical neurological involvement by visual evoked potential (VEP) measurements and nerve conduction studies (NCS) and explore the relationship between neurological electrophysiological findings and the severity of COVID-19 infection. METHODS: Seventy-six patients recovered from COVID-19 infection, and 44 healthy controls were enrolled in the study. Patients were assessed for clinical and demographic parameters. NCS and VEP analyses were performed to detect any peripheral neuropathy or optic neuropathy in both groups. RESULTS: None of the COVID-19 patients had electrophysiological evidence of peripheral neuropathy. However, patients with COVID-19 pneumonia had significant abnormalities in several peripheral nerve measurements compared to patients without pneumonia. Although P100 parameters did not differ significantly between patients and controls, 12 patients with COVID-19 had prolonged P100 latencies. CONCLUSIONS: We detected subclinical afferent visual pathway abnormality evaluated by VEP analysis. In addition, we found subtle electrophysiological features in the NCS of the patients presented with COVID-19 pneumonia. However, our findings did not fortify the diagnosis of peripheral neuropathy or optic neuropathy. Further studies are needed to determine the characteristics of COVID-19-related peripheral neuropathy/optic neuropathy whether it has distinct clinical features and disease course.

Is psychological distress associated with carpal tunnel syndrome symptoms and nerve conduction study findings? A case-control study from Syria.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve at the wrist which causes severe symptoms. However, psychological aspects can affect patients' perception of this pain and can cause similar pain in some instances. This study aims to determine the association between symptoms severity, functional status, and nerve conduction studies (NCS) of adult patients with CTS and their anger, anxiety, and depression status. METHODS: This case-control study was conducted in clinics in Damascus, Syria. Controls were frequency matched by gender and age from a general clinic. Interviews based on questionnaires were used that included the Boston Carpal Tunnel Questionnaire (BCTQ-A), Hospital Anxiety and Depression Scale (HADS), Dimensions of Anger Reactions Scale-5 (DAR-5), and NCS. RESULTS: Overall, 242 patients (121 cases) were included in this study. Cases with CTS had significantly higher anxiety and depression when compared to controls, but not higher anger. Cases with higher anxiety, depression, and anger had significantly more CTS symptoms and less functional status. Anxiety was also higher in cases with normal NCS in the case group. When using regression, anxiety and depression remained significantly associated with having CTS. CONCLUSION: Anxiety and depression are more prominent with CTS. Furthermore, having anxiety and depression were associated with more CTS symptoms in the hand. Having anger was also associated with more CTS symptoms among cases. These findings emphasize the importance of psychological aspects when having hand pain or CTS symptoms as these patients might have these symptoms despite having normal NCS.

Optimizing the operation of an electrodiagnostic laboratory during the COVID-19 pandemic: A 6-month single-center experience.

INTRODUCTION/AIMS: The initial surge of the coronavirus disease-2019 (COVID-19) pandemic in early 2020 led to widespread cancellation of elective medical procedures in the United States, including nonurgent outpatient and inpatient electrodiagnostic (EDx) studies. As certain regions later showed a downtrend in daily new cases, EDx laboratories have reopened under the guidance of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). In our reopening experience guided by the AANEM, we measured relevant outcomes to determine further workflow adaptations. We aimed to detail our experience and share the lessons learned. METHODS: We reviewed the clinical volumes, billing data, diagnosis distributions, and rates of COVID-19 exposure and transmission among patients and staff in our EDx laboratory during the first 6 months of reopening, starting on June 1, 2020. For context, we detailed the recent AANEM guidelines we adopted at our laboratory, supplemented by other consensus statements. RESULTS: We completed 816 outpatient studies from June 1 to December 1, 2020, reaching 97% of the total volume and 97% of total billing compared with the same time period in 2019. The average relative value units per study were similar. There were no major shifts in diagnosis distributions. We completed 10 of 12 requested inpatient studies during this period. There were no known COVID-19 transmissions between patients and staff. DISCUSSION: Our experience suggests that it is possible to safely operate an EDx laboratory under the guidance of the AANEM and other experts, with clinical volume and billing rates comparable to pre-pandemic baselines.

Treatment related fluctuation and response to intravenous immunoglobulin therapy in post COVID-19 Guillain-Barre syndrome.

Treatment related fluctuation (TRF) poses a special challenge in the treatment of Guillain-Barre syndrome (GBS). Many cases of GBS following COVID-19 infection have been reported in literature till date, but treatment related fluctuation (TRF) in post COVID-19 GBS has not been reported till date. We report a 35-year-old male patient who developed GBS following COVID-19 infection and had TRF after intravenous immunoglobulin (IV-IG) therapy. He required ventilator support but repeat IV-IG therapy led to complete recovery. Significant proximal muscle involvement, cranial nerve palsy, no antecedent diarrhea and absence of anti-GM1 antibodies are important predictors of TRF in GBS and need to be recognized early in the course of this illness. Early recognition of TRF and differentiating it from other forms of immune mediated neuropathy such as acute onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) are important for prognostication and management.

Myopathic changes in patients with long-term fatigue after COVID-19.

OBJECTIVE: To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). METHODS: Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. RESULTS: qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. CONCLUSIONS: Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. SIGNIFICANCE: Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.

Guillain Barré Syndrome and its variants as a manifestation of COVID-19: A systematic review of case reports and case series.

BACKGROUND: The COVID-19 pandemic caused by SARS-COV-2 began in Wuhan, China in December 2019. Reports of COVID-19 with central (CNS) and peripheral nervous (PNS) system manifestations are emerging. In this systematic review, we compared and summarized the demographics, clinical features, Brighton criteria, immunological and laboratory findings with a focus on modified Erasmus GBS Outcome Score (mEGOS) in SARS-CoV-2 patients with GBS and its variants. METHODS: Based on PRISMA guidelines, we searched three databases (PubMed, Scopus, and Google Scholar) for studies on COVID-19 and GBS between December 1, 2019 to July 15, 2020. For descriptive analysis, we studied two groups with: 1) acute inflammatory demyelinating polyradiculoneuropathy (AIDP) variant, and 2) Non-AIDP/Other variants. We compared mEGOS scores for patients in both groups along with other key clinical features. RESULTS: Of the 50 GBS cases identified from 37 studies, 33 (66%) had acute inflammatory demyelinating polyradiculopolyneuropathy (AIDP) while 17 (34%) were of other (non-AIDP) variants. There mEGOS scores did not differ between AIDP patients and AMAN/AMSAN patients. Majority of the AIDP (66.7%) and AMAN/AMSAN (57.2%) patients belonged to Brighton level 1 indicating maximum diagnostic certainty. CONCLUSION: To our knowledge, this is among the first reviews that includes GBS variants and the clinical prediction tool mEGOS for prognostication in COVID-19 patients. Further research is needed to assess whether IVIG is preferable over plasmapheresis in this population of GBS patients. It would also be crucial to follow these patients over time to identify the long-term disability as well as treatment outcomes.

COVID-19-associated Guillain-Barré syndrome: The early pandemic experience.

Guillain-Barré syndrome (GBS) is an inflammatory polyradiculoneuropathy associated with numerous viral infections. Recently, there have been many case reports describing the association between coronavirus disease-2019 (COVID-19) and GBS, but much remains unknown about the strength of the association and the features of GBS in this setting. We reviewed 37 published cases of GBS associated with COVID-19 to summarize this information for clinicians and to determine whether a specific clinical or electrodiagnostic (EDx) pattern is emerging. The mean age (59 years), gender (65% male), and COVID-19 features appeared to reflect those of hospitalized COVID-19 patients early in the pandemic. The mean time from COVID-19 symptoms to GBS symptoms was 11 days. The clinical presentation and severity of these GBS cases was similar to those with non-COVID-19 GBS. The EDx pattern was considered demyelinating in approximately half of the cases. Cerebrospinal fluid, when assessed, demonstrated albuminocytologic dissociation in 76% of patients and was negative for severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) in all cases. Serum antiganglioside antibodies were absent in 15 of 17 patients tested. Most patients were treated with a single course of intravenous immunoglobulin, and improvement was noted within 8 weeks in most cases. GBS-associated COVID-19 appears to be an uncommon condition with similar clinical and EDx patterns to GBS before the pandemic. Future studies should compare patients with COVID-19-associated GBS to those with contemporaneous non-COVID-19 GBS and determine whether the incidence of GBS is elevated in those with COVID-19.

SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with a favourable outcome.

BACKGROUND AND PURPOSE: The spectrum of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), includes different neurologic manifestations of the central and peripheral nervous system. METHODS: From March through April 2020, in two university hospitals located in western Switzerland, we examined three patients with Guillain-Barré syndrome (GBS) following SARS-CoV-2. RESULTS: These cases were characterized by a primary demyelinating electrophysiological pattern (Acute inflammatory demyelinating polyneuropathy or AIDP) and a less severe disease course compared to recently published case series. Clinical improvement was observed in all patients at week five. One patient was discharged from hospital after full recovery with persistence of minor neurological signs (areflexia). Two of the three patients remained hospitalized: one was able to walk and the other could stand up with assistance. CONCLUSIONS: We report three cases of typical GBS (AIDP) occurring after SARS-CoV-2 infection and presenting with a favourable clinical course. Given the interval between COVID-19-related symptoms and neurological manifestations (mean of 15 days) we postulate a secondary immune-mediated mechanism rather than direct viral damage.

Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children.

Importance: Neurological manifestations have been reported in adults with coronavirus disease 2019 (COVID-19), which is caused by the highly pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To report the neurological manifestations of children with COVID-19. Design, Setting, and Participants: In this case-series study, patients younger than 18 years who presented with SARS-CoV-2 infection and neurological symptoms to Great Ormond Street Hospital for Children (London, UK) between March 1, 2020, and May 8, 2020, were included after infection was confirmed by either a quantitative reverse transcription-polymerase chain reaction assay by nasopharyngeal swab or a positive test result for IgG antibodies against SARS-CoV-2 in serum. Main Outcomes and Measures: Clinical and paraclinical features were retrieved from electronic patient records. Results: Of the 27 children with COVID-19 pediatric multisystem inflammatory syndrome, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients required intensive care unit admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome. Splenium signal changes were seen in all 4 patients on magnetic resonance imaging of the brain. In the 2 patients whose cerebrospinal fluid was tested, samples were acellular, with no evidence of infection on polymerase chain reaction or culture (including negative SARS-CoV-2 polymerase chain reaction results) and negative oligoclonal band test results. In all 3 patients who underwent electroencephalography, a mild excess of slow activity was found. Tests for N-methyl-d-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies had negative results in all patients. In all 3 patients who underwent nerve conduction studies and electromyography, mild myopathic and neuropathic changes were seen. Neurological improvement was seen in all patients, with 2 making a complete recovery by the end of the study. Conclusions and Relevance: In this case-series study, children with COVID-19 presented with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19.