Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

Machine learning classification of multiple sclerosis in children using optical coherence tomography.

BACKGROUND: In children, multiple sclerosis (MS) is the ultimate diagnosis in only 1/5 to 1/3 of cases after a first episode of central nervous system (CNS) demyelination. As the visual pathway is frequently affected in MS and other CNS demyelinating disorders (DDs), structural retinal imaging such as optical coherence tomography (OCT) can be used to differentiate MS. OBJECTIVE: This study aimed to investigate the utility of machine learning (ML) based on OCT features to identify distinct structural retinal features in children with DDs. METHODS: This study included 512 eyes from 187 (neyes = 374) children with demyelinating diseases and 69 (neyes = 138) controls. Input features of the analysis comprised of 24 auto-segmented OCT features. RESULTS: Random Forest classifier with recursive feature elimination yielded the highest predictive values and identified DDs with 75% and MS with 80% accuracy, while multiclass distinction between MS and monophasic DD was performed with 64% accuracy. A set of eight retinal features were identified as the most important features in this classification. CONCLUSION: This study demonstrates that ML based on OCT features can be used to support a diagnosis of MS in children.

Pandemic-associated mental health changes in youth with neuroinflammatory disorders.

BACKGROUND: Children with neuroinflammatory disorders have high rates of anxiety and depression, alongside low rates of physical activity. Given general concerns for mental and physical health in children during the COVID-19 pandemic lockdown, here we sought to understand how sleep, anxiety, depression, and physical activity changed with the lockdown in children with neuroinflammatory disorders. We hypothesized that outcomes would worsen during the lockdown, and that they would differ by underlying disorder category and age. METHODS: Patients attending a specialized neuroinflammatory clinic (n = 314) completed questionnaires (n = 821 responses; Jan 2017-Aug 2020) assessing sleep, anxiety, depression, and physical activity. Respondents had either: childhood-onset chronic or recurrent neuroinflammatory disorders (CRNI), a history of Autoimmune Encephalitis (AE) or Monophasic Acquired Demyelinating Syndromes (monoADS). We performed linear mixed models to examine the association between our outcome measures (sleep, anxiety, depression, and physical activity) and categories of disorder type, sex, age, physical activity, relapses, and time (pre- vs. post- COVID-19 lockdown). Participant ID acted as a random effect, to account for repeated measures. RESULTS: Sleep significantly increased in the first 6 months of the COVID-19 lockdown (F(1, 544)=56.85, P<0.001,). Across the whole group, anxiety and depression did not change with the pandemic, but we found differing trends by age category. Anxiety decreased in teenagers (≥13y) (Z = 3.96, P<0.001), but not for pre-teens. Depression remained higher in teenagers than preteens across both timepoints (F(1, 597)=6.30, p = 0.012). Physical activity levels did not change with the pandemic in comparison to pre-pandemic (F(1, 629)=1.92, P = 0.166). Anxiety was higher in inactive individuals regardless of timing (F(2, 547)=3.74, p = 0.024). CONCLUSION: For youth with neuroinflammatory disorders, the COVID-19 pandemic lockdown resulted in increased hours of nighttime sleep but did not result in significant overall changes in self-reported anxiety or depression. Pre-lockdown, teenagers had higher depression and anxiety scores than preteens. Post-lockdown, anxiety and depression scores decreased in teenagers compared to pre-teens. Physical activity was low both pre- and post-lockdown, and rates of anxiety were higher for inactive participants at both timepoints. Differences based on age suggest that younger children (<13 years) were more negatively affected by the pandemic than older children (≥ 13 years).

Association of outcomes in acute flaccid myelitis with identification of enterovirus at presentation: a Canadian, nationwide, longitudinal study.

BACKGROUND: Acute flaccid myelitis (AFM) is characterised by rapid onset of limb weakness with spinal cord grey-matter abnormalities on MRI scan. We aimed to assess whether detection of enterovirus in respiratory or other specimens can help predict prognosis in children with AFM. METHODS: In this nationwide, longitudinal study, we evaluated the significance of detection of enterovirus in any sample in predicting outcomes in a cohort of Canadian children younger than 18 years presenting with AFM to tertiary paediatric hospitals in Canada in 2014 and 2018. All patients fulfilled the 2015 US Centers for Disease Control and Prevention case definition for definite AFM or probable AFM. Clinical data, laboratory findings, treatment, and neuroimaging results were collected (follow up period up to 5 years). We assessed neurological function and motor outcomes using Kurtzke's Expanded Disability Status Scale (EDSS) and a Weakest Limb Score. FINDINGS: 58 children with AFM (median age 5·1 years, IQR 3·8-8·3) were identified across five of Canada's ten provinces and three territories. 25 (43%) children had enterovirus detected in at least one specimen: 16 (64%) with EV-D68, two (8%) with EV-A71, two (8%) with coxsackievirus, 10 (40%) with untyped enterovirus. Children who were enterovirus positive were more likely than those that were negative to have had quadriparesis (12 [48%] of 25 vs four [13%] of 30; p=0·028), bulbar weakness (11 [44%] of 25 vs two [7%] of 30; p=0·028), bowel or bladder dysfunction (14 [56%] of 25 vs seven [23%] of 30; p=0·040), cardiovascular instability (nine [36%] of 25 vs one [3%] of 30; p=0·028), and were more likely to require intensive care unit admission (13 [52%] of 25 vs 5 [17%] of 30; p=0·028). On MRI, most children who were enterovirus positive showed brainstem pontine lesions (14 [61%] of 23), while other MRI parameters did not correlate with enterovirus status. Median EDSS of enterovirus positive (EV+) and enterovirus negative (EV-) groups was significantly different at all timepoints: baseline (EDSS 8·5, IQR 4·1-9·5 vs EDSS 4·0, IQR 3·0-6·0; p=0·0067), 3 months (EDSS 4·0, IQR 3·0-7·4 vs EDSS 3·0, IQR 1·5-4·3; p=0·0067), 6 months (EDSS 3·5, IQR 3·0-7·0 vs EDSS 3·0, IQR 1·0-4·0; p=0·029), and 12 months (EDSS 3·0, IQR 3·0-6·9 vs EDSS 2·5 IQR 0·3-3·0; p=0·0067). Kaplan-Meier survival analysis of a subgroup of patients showed significantly poorer motor recovery among children who tested positive for enterovirus than for those who tested negative (p=0·037). INTERPRETATION: Detection of enterovirus in specimens from non-sterile sites at presentation correlated with more severe acute motor weakness, worse overall outcomes and poorer trajectory for motor recovery. These results have implications for rehabilitation planning as well as counselling of families of children with these disorders. The findings of this study support the need for early testing for enterovirus in non-CNS sites in all cases of AFM. FUNDING: None.

Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey: Focus on Herpes Simplex Type 1.

INTRODUCTION: The objective of this study was to determine the incidence of herpes simplex encephalitis (HSE), known as the most common, potentially mortal, and treatable cause of sporadic encephalitis, in a sample Turkish population. METHODS: The demographic, clinical, laboratory, imaging, electrophysiology, and polymerase chain reaction (PCR) DNA results of patients examined with a pre-diagnosis of encephalitis were retrospectively examined. RESULTS: A total of 68 patients were included in the study. The most common presenting symptom was altered behavior (67.6%), while temporal T2 hyperintensity was determined in the magnetic resonance imaging (MRI) of 27.9% of the patients and electroencephalography (EEG) abnormalities were determined in 66.2% of the patients. Lymphocytic pleocytosis was determined in the cerebrospinal fluid (CSF) in 35 patients. Fifty-seven patients had been diagnosed with viral encephalitis, 3 with bacterial meningitis, 3 with tuberculous meningitis, 2 with sporadic Creutzfeld-Jakob disease, 2 with acute disseminating encephalomyelitis, and 1 with Brucella encephalitis. Seven (10.2%) cases of viral encephalitis were found to be positive for herpes simplex virus (HSV) DNA by PCR. CONCLUSION: Viral encephalitis is the most common cause of infectious encephalitis; however, other atypical causes should also be noted. Negative PCR results for HSV DNA should not exclude the need for antiviral therapy in patients with a strong pre-diagnosis of HSE because diagnostic modalities, including PCR, may fail in acute settings and HSE remains the sole treatable cause of infectious encephalitis.

Evaluation of interictal autonomic function during attack and remission periods in cluster headaches.

OBJECTIVE: To investigate which part of the autonomic system is mainly involved and assess the sensitivity of face sympathetic skin response in cluster headache. MATERIAL AND METHODS: The study sample consisted of 19 drug-free cluster headache patients (16 males, three females) and 19 healthy volunteers. Demographic features and pain characteristics were thoroughly identified. Dysautonomic symptoms were evaluated during attack and remission periods of cluster headache patients. Orthostatic hypotension, R-R interval variation and sympathetic skin responses obtained from the face and four extremities were evaluated and the sensitivity of face sympathetic skin responses was assessed in contrast to extremity sympathetic skin responses. RESULTS: All sympathetic skin responses of face and extremities could be obtained during attack and remission periods. On the symptomatic side, mean latency of face sympathetic skin responses was longer compared to the asymptomatic side and controls (p = 0.02, p = 0.004). There were no differences in latency or amplitude of extremity sympathetic skin responses between symptomatic and asymptomatic sides and controls. No significant relationship was determined between sympathetic skin responses, R-R interval variation, orthostatic hypotension and cluster headache clinical features. CONCLUSION: Sympathetic hypoactivity of the face seems to predominate the pathophysiology of cluster headache. Face sympathetic skin responses might be more sensitive compared to extremity sympathetic skin response in demonstrating dysautonomic symptoms in cluster headache patients.

Forehead sympathetic skin responses in determining autonomic involvement in Parkinson's disease.

OBJECTIVE: The purpose of this study was to evaluate forehead sympathetic skin response (SSR) and demonstrate any differences with extremity SSR in determining autonomic nervous system (ANS) involvement in patients with Parkinson's disease (PD). METHODS: Twenty early stage, 20 advanced stage idiopathic PD patients and 20 healthy controls participated in this study. SSR of forehead, hands and feet, heart rate variability (HRV), orthostatic intolerance, QT intervals and dysautonomic symptoms were evaluated. RESULTS: Absent forehead SSR was determined unilaterally in 4, bilaterally in 7 early stage patients, and unilaterally in 4, bilaterally in 8 advanced stage PD patients; there was significant difference between early and advanced stage PD and control groups in terms of the lack of SSR (p=0.000). Absent extremity SSR was determined in at least 1 extremity of 3 advanced stage PD patients, and none of the early stage PD patients. No difference was noted in HRV at rest between early and advanced stage PD and control groups (p=0.218); but HRV at deep breathing was lower in both early and advanced PD patients compared to controls (p=0.014, p=0.002, respectively). CONCLUSION: Forehead SSR is more sensitive in determining ANS dysfunction not only in late but also in early stage of PD. SIGNIFICANCE: With further supportive research, forehead SSR might be used as a simple diagnostic electrophysiological test in the early diagnosis of ANS dysfunction enabling proper treatment and increasing the quality of life of PD patients.