Guillain-Barre Syndrome After Two COVID-19 Vaccinations: Two Case Reports With Follow-up Electrodiagnostic Study.

Guillain-Barre syndrome (GBS) is an immune-mediated acute polyradiculoneuropathy and commonly occurs after a preceding infection or immunization sequalae. Following the severe acute respiratory syndrome-coronavirus-2 virus pandemic with co-introduction of massive vaccinations, several GBS cases associated with coronavirus disease 2019 (COVID-19) infection per se or after vaccination for COVID-19 were reported internationally. Herein, we report two cases of Korean GBS presenting with tetraplegia after two different COVID-19 vaccinations (42-year old man by AstraZeneca and 48-year woman by Pfizer vaccines) within four weeks after vaccination. The patients were diagnosed with clinical examination, serial electromyography, and compatible laboratory results and improved after comprehensive rehabilitative treatment and intravenous immunoglobulin therapy. Furthermore, we performed an electrodiagnostic follow-up study of each case to examine their unique characteristics.

Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients.

Mutations in adaptor protein complex-4 (AP-4) genes have first been identified in 2009, causing a phenotype termed as AP-4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype-phenotype correlation of the AP-4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease-causing variants in AP-4 complex subunits, using next-generation sequencing. Furthermore, by comparing genotype-phenotype findings of those affected individuals with previously reported patients, we further refine the genotype-phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP-4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders.

MR Spectroscopy of the Cervical Spinal Cord in Chronic Spinal Cord Injury.

Purpose To investigate metabolic changes in chronic spinal cord injury (SCI) by applying MR spectroscopy in the cervical spinal cord. Materials and Methods Single-voxel short-echo spectroscopic data in study participants with chronic SCI and healthy control subjects were prospectively acquired in the cervical spinal cord at C2 above the level of injury between March 2016 and January 2017 and were compared between groups. Concentrations of total N-acetylaspartate (tNAA), myo-inositol (mI), total choline-containing compounds (tCho), creatine, and glutamine and glutamate complex were estimated from the acquired spectra. Participants were assessed with a comprehensive clinical evaluation investigating sensory and motor deficits. Correlation analysis was applied to investigate relationships between observed metabolic differences, lesion severity, and clinical outcome. Results There were 18 male study participants with chronic SCI (median age, 51 years; range, 30-68 years) and 11 male healthy control subjects (median age, 45 years; range, 30-67 years). At cervical level C2, tNAA/mI and tCho/mI ratios were lower in participants with SCI (tNAA/mI: -26%, P = .003; tCho/mI: -18%; P = .04) than in healthy control subjects. The magnitude of difference was greater with the severity of cord atrophy (tNAA/mI: R2 = 0.44, P = .003; tCho/mI: R2 = 0.166, P = .09). Smaller tissue bridges at the lesion site correlated with lower ratios of tNAA/mI (R2 = 0.69, P = .006) and tCho/mI (R2 = 0.51, P = .03) at the C2 level. Lower tNAA/mI and tCho/mI ratios were associated with worse sensory and motor outcomes (P < .05). Conclusion Supralesional metabolic alterations are observed in chronic spinal cord injury, likely reflecting neurodegeneration, demyelination, and astrocytic gliosis in the injured cervical cord. Lesion severity and greater clinical impairment are both linked to the biochemical changes in the atrophied cervical cord after spinal cord injury. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Lin in this issue.

Spasticity and preservation of skeletal muscle mass in people with spinal cord injury.

STUDY DESIGN: Cross-sectional OBJECTIVE: To investigate the association between skeletal muscle mass and spasticity in people with spinal cord injury (SCI). SETTING: Tertiary level hospital in Seoul, Korea METHODS: Spasticity was evaluated in 69 participants with SCI using the spasticity sum score (SSS), Penn Spasm Frequency Scale (PSFS), and Spinal Cord Assessment Tool for Spastic Reflexes (SCATS). Skeletal muscle mass was measured using a dual-energy X-ray absorptiometry scanner, and skeletal muscle index was calculated by dividing skeletal muscle mass by height squared. Laboratory parameters including hemoglobin, albumin, creatinine, fasting glucose, and cholesterol were measured. Spearman's correlation analysis was performed to assess the association between the skeletal muscle mass and spasticity scales. Multiple linear regression analysis was used to present the independent association between them. RESULTS: The participants' mean age was 41.8 years; 54 (78.3%) were male, and 46 (66.7%) were tetraplegic. Skeletal muscle index of lower extremities was significantly correlated with all spasticity scales. Spearman's correlation coefficients were 0.468, 0.467, 0.555, 0.506, and 0.474 for SSS, PSFS, SCATS clonus, SCATS flexor, and SCATS extensor with p-values < 0.001, respectively. After adjustment for age, sex, level of injury, body mass index, and serum creatinine, all spasticity scales were significantly associated with skeletal muscle index of lower extremities in multiple regression analysis. Standardized coefficients were 0.228, 0.274, 0.294, 0.210, and 0.227 for SSS, PSFS, SCATS clonus, SCATS flexor, and SCATS extensor. CONCLUSIONS: Spasticity was significantly correlated with the skeletal muscle mass even after adjusting for possible confounders. Spasticity may need to be considered as an influencing factor in interventions such as electrical stimulation to preserve skeletal muscle mass.

Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis.

We ascertained two unrelated consanguineous families with two affected children each having microcephaly, refractory seizures, intellectual disability, and spastic quadriparesis. Magnetic resonance imaging showed atrophy of cerebrum, cerebellum and spinal cord, prominent cisterna magna, symmetric T2 hypo-intensities in the bilateral basal ganglia and thinning of corpus callosum. Whole-exome sequencing of three affected individuals revealed c.105C>A [p.(Tyr35Ter)] variant in AIMP2. The variant lies in a common homozygous region of 940 kb on chromosome 7 and is likely to have been inherited from a common ancestor. The phenotype noted in our subjects' shares marked similarity with that of hypomyelinating leukodystrophy-3 caused by mutations in closely related gene AIMP1. We hereby report the first human disease associated with deleterious mutations in AIMP2.

WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome.

The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.

Guillain-Barre syndrome complicating chikungunya virus infection.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which presents with symptoms of fever, rash, arthralgia, and occasional neurologic disease. While outbreaks have been earlier reported from India and other parts of the world, the recent outbreak in India witnessed more than 1000 cases. Various systemic and rarely neurological complications have been reported with CHIKV. We report two cases of Guillain-Barré syndrome (GBS) with CHIKV. GBS is a rare neurological complication which may occur after subsidence of fever and constitutional symptoms by several neurotropic viruses. We describe two cases of severe GBS which presented with rapidly progressive flaccid quadriparesis progressing to difficulty in swallowing and breathing. Both required mechanical ventilation and improved partly with plasmapharesis. The cases emphasize on (1) description of the rare complication in a setting of outbreak with CHIKV, (2) acute axonal as well as demyelinating neuropathy may occur with CHIKV, (3) accurate identification of this entity during outbreaks with dengue, both of which are vector borne and may present with similar complications.

Recessive mutations in SLC35A3 cause early onset epileptic encephalopathy with skeletal defects.

We describe the clinical and whole genome sequencing (WGS) study of a non-consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression-burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability. General examination showed distal arthrogryposis predominant in the hands in both siblings and severe left dorso-lumbar convex scoliosis in one. WGS of the siblings-parents quartet identified novel compound heterozygous mutations in SLC35A3 in both children. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine transporter. With this study, we add SLC35A3 to the gene list of epilepsies. Neurological symptoms and skeletal abnormalities might result from impaired glycosylation of proteins involved in normal development and function of the central nervous system and skeletal apparatus.

Unusual case of tetraparesis in a patient with systemic lupus erythematosus.

We describe the case of a 67-year-old Asian female patient suffering from severe systemic lupus erythematosus (SLE), including biopsy-proven glomerulonephritis, since the age of 40 who was admitted for tetraparesis. Neurological examination confirmed proximal muscular weakness, hypoesthesia and diminished tendon reflexes. The patient suffered from extremely severe Jaccoud's arthropathy. Magnetic resonance imaging (MRI) demonstrated severe narrowing of the upper spinal canal due to a soft tissue mass surrounding the odontoid process, assumed to be a synovial pannus, causing myelopathy. The patient was treated with three intravenous pulses of methylprednisolone with prompt and full clinical recovery. Follow-up MRI confirmed considerable regression of the pannus. Inflammatory transverse myelopathy is the most common explanation for para/tetraparesis in SLE. However, in this case, the symptoms were caused by atlantoaxial synovitis, which is more typical for rheumatoid arthritis.

Pyomyositis Causing Temporary Quadriparesis During Induction Therapy for Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

Pyomyositis (PM) is a purulent infection of skeletal muscle. It is often associated with immunosuppression in temperate climates. Herein, we report a case of PM causing temporary quadriparesis in a 14-year-old girl undergoing induction therapy for acute lymphoblastic leukemia and we review the reported pediatric cases associated with induction therapy for hematologic malignancies. Early symptoms of PM can be mistaken for the side effects of chemotherapeutic agents. Greater awareness of the clinical picture of PM will aid in early diagnosis and treatment. With appropriate medical therapy and timely abscess drainage, morbidity and mortality is greatly reduced.

Is sport practice a risk factor for shoulder injuries in tetraplegic individuals?

STUDY DESIGN: A retrospective cohort. OBJECTIVES: To report the incidence rates of shoulder injuries diagnosed with magnetic resonance imaging (MRI) in tetraplegic athletes and sedentary tetraplegic individuals. To evaluate whether sport practice increases the risk of shoulder injuries in tetraplegic individuals. SETTING: Campinas, Sao Paulo, Brazil. METHODS: Ten tetraplegic athletes with traumatic spinal cord injury were selected among quad rugby athletes and had both the shoulders evaluated by MRI. They were compared with 10 sedentary tetraplegic individuals who were submitted to the same radiological protocol. RESULTS: All athletes were male with a mean age of 32.1 years (range 25-44 years, s.d.=6.44). Time since injury ranged from 6 to 17 years, with a mean value of 9.7 years and s.d. of 3.1 years. All sedentary individuals were male with a mean age of 35.9 years (range 22-47 years, s.d.=8.36). Statistical analysis showed a protective effect of sport in the development of shoulder injuries, with a weak correlation for infraspinatus and subscapularis tendinopathy (P=0.09 and P=0.08, respectively) and muscle atrophy (P=0.08). There was a strong correlation for acromioclavicular joint (ACJ) and labrum injuries (P=0.04), with sedentary individuals at a higher risk for these injuries. CONCLUSION: Tetraplegic athletes and sedentary individuals have a high incidence of supraspinatus tendinosis, bursitis and ACJ degeneration. Statistical analysis showed that there is a possible protective effect of sport in the development of shoulder injuries. Weak evidence was encountered for infraspinatus and subscapularis tendinopathy and muscle atrophy (P=0.09, P=0.08 and P=0.08, respectively). Strong evidence with P=0.04 suggests that sedentary tetraplegic individuals are at a greater risk for ACJ and labrum injuries.

Written production in a case of locked-in syndrome with bilateral corticopontic degeneration.

Patients in locked-in syndrome show normal or near normal mental abilities that contrast with the limited motor capacity that hinders voluntary communication. However, eye movements and blinking are usually preserved and can be used to establish a communication system. We report an exceptional case of locked-in syndrome. The aetiology was basilar thrombosis consecutive to a cervical manipulation. In addition, brain MRI performed 23 years later showed a ventral pontine stroke with bilateral corticopontic degeneration. In this study the patient was able to produce written output using a chin-controlled Morse system decoded by a computer. A detailed linguistic analysis of text written over 20 years by the patient was carried out. The data demonstrate that improvements in language performance can be observed even in patients with brain lesions in areas associated with high-level cognitive processes. The data show a decrease of typing, grammatical and lexical errors over time, use of less frequent words, and an increase of more complex linguistic structures. This paper adds to previous findings confirming the value of daily practice and rehabilitation to enhance quality of life in this group of patients.

Selective effects of baclofen on use-dependent modulation of GABAB inhibition after tetraplegia.

Baclofen is a GABAB receptor agonist commonly used to relief spasticity related to motor disorders. The effects of baclofen on voluntary motor output are limited and not yet understood. Using noninvasive transcranial magnetic and electrical stimulation techniques, we examined electrophysiological measures probably involving GABAB (long-interval intracortical inhibition and the cortical silent period) and GABAA (short-interval intracortical inhibition) receptors, which are inhibitory effects mediated by subcortical and cortical mechanisms. We demonstrate increased active long-interval intracortical inhibition and prolonged cortical silent period during voluntary activity of an intrinsic finger muscle in humans with chronic incomplete cervical spinal cord injury (SCI) compared with age-matched controls, whereas resting long-interval intracortical inhibition was unchanged. However, long-term (~6 years) use of baclofen decreased active long-interval intracortical inhibition to similar levels as controls but did not affect the duration of the cortical silent period. We found a correlation between signs of spasticity and long-interval intracortical inhibition in patients with SCI. Short-interval intracortical inhibition was decreased during voluntary contraction compared with rest but there was no effect of SCI or baclofen use. Together, these results demonstrate that baclofen selectively maintains use-dependent modulation of largely subcortical but not cortical GABAB neuronal pathways after human SCI. Thus, cortical GABA(B) circuits may be less sensitive to baclofen than spinal GABAB circuits. This may contribute to the limited effects of baclofen on voluntary motor output in subjects with motor disorders affected by spasticity.

[Sequential MRI imaging of progressive bilateral rostro-caudal medullary infarction]. / Infarctus bulbaire paramédian bilatéral d'évolution progressive: à propos de deux cas documentés en imagerie par résonance magnétique séquentielle.

Bilateral medial medullary infarction is exceptional. Initial symptoms can be misleading, even for a trained neurologist. We report two patients who presented progressive quadriplegia, anarthia and dysphagia. Sequential MRI showed progressive constitution of the characteristic "heart appearance" sign.

Clinical characteristics and outcome in the acute phase of ischemic locked-in syndrome: case series of twenty patients with ischemic LIS.

BACKGROUND: Locked-in syndrome (LIS) is a condition characterized by quadriplegia and anarthria. The most common cause is a ventral pontine lesion due to atherosclerotic basilar artery disease. METHODS: Cases with LIS were prospectively identified among the patients with acute ischemic stroke over 3 years, between 2009 and 2011. Clinical characteristics, topographic localization of lesions, and outcome were determined during the first 6 months from onset of LIS. RESULTS: Our case series consists of 20 patients (mean age 62 ± 10 years; range 46-82). Initially 16 patients had a reduced level of consciousness (mean 3 days; range 1-15). Respiratory disturbance, mainly as impairment of the breathing pattern, was noted in all cases. Five patients died within the first 10 days due to stroke progression or cardiac arrest. In the remaining cases the most frequent causes of death were pulmonary infections and sepsis. Overall mortality in the acute phase of LIS is 75%, and the median survival time is 42 days. There was a statistically significant association between the more extensive parenchymal brain stem lesions and observed mortality. CONCLUSIONS: Ischemic LIS is commonly caused by an acute complete occlusion of the basilar artery due to atherosclerotic lesions in intracranial vertebrobasilar vessels. Mortality remains high in the acute phase of the disease.

Basal sympathetic activity to the microcirculation in tetraplegic man revealed by wavelet transform of laser Doppler flowmetry.

BACKGROUND: The 1984/86 published neurogram results showing only rare sympathetic nerve activity (SNA) to the muscles and skin in tetraplegia are still accepted. The present study by a different method attempted to confirm or deny those findings. METHODS AND RESULTS: The effect of basal SNA to the microcirculation of the feet and calf in 10 complete (AIS A) traumatic tetraplegic and 10 healthy age matched subjects were evaluated by wavelet transform of laser Doppler flowmetry (LDF) recordings. The results clearly indicated there is significant basal SNA from the decentralized spinal cord in tetraplegia. In addition, wavelet analysis allowed a study of other influences on the microcirculation besides SNA. Collectively, in tetraplegia compared with controls, the powers of the low frequency oscillations in blood flow were reduced; in that the endothelium caused less vasodilatation while the SNA and intrinsic vascular smooth muscles induced smaller degrees of vasoconstriction. However, the high frequency and especially the cardiac powers were greater. The latter presenting an obvious important factor for the preservation of blood flow in the microcirculation. CONCLUSIONS: It is suggested that basal SNA to the cutaneous microcirculation occurs in complete tetraplegia, and the significant levels of circulating noradrenaline reported by others indicate this is also true in other parts of the body. This may explain the usual absence of severe, incapacitating, autonomic deficiency in this condition.

Predictive factors of long-term mortality of persons with tetraplegic spinal cord injury: an 11-year French prospective study.

STUDY DESIGN: Longitudinal study with mortality follow-up. OBJECTIVE: Identify predictive factors for long-term mortality following tetraplegic spinal cord injury (TSCI). SETTING: The Tetrafigap survey is a multi-centre epidemiological survey on the long-term outcome of persons with TSCI, initiated in France in 1995 with the participation of 35 rehabilitation centres. METHODS: The mortality follow-up involves 1241 persons with TSCI who were admitted to one of the study rehabilitation units at the initial phase and who completed the initial self-administered questionnaire. There were 226 observed deaths (18.2%) during an 11-year period. Logistic regression methods, with estimates of odds ratios (ORs), incorporating clinical, functional and social participation data were used to determine the factors related to mortality. This was followed by multivariate analysis to determine the best predictive factors for long-term mortality. RESULTS: Risk of death increases significantly with age but not with the time elapsed since the accident. The risk of death is higher in men. Interestingly, clinical variables are not the best predictors of long-term mortality. Instead, the significant effect of poor social participation (being single, infrequent contact with friends) and functional limitations (full assistance required with dressing or eating) persists after adjustment for other variables. CONCLUSION: Once the medical situation becomes more stable, factors related to the long-term mortality of persons with TSCI are not exactly identical to those observed in the short acute-phase and during the first year after the accident. Social participation has a significant effect on mortality.

Cortical blindness associated with autonomic dysreflexia in a man with tetraplegia: a rare but serious complication.

CONTEXT: To describe a case of a 44-year-old man with complete C4 tetraplegia who developed transient cortical blindness in the subacute setting following episodes of autonomic dysreflexia. FINDINGS: Transient cortical blindness the day after surgery for appendicitis that had resulted in severe autonomic dysreflexia (AD) requiring aggressive blood pressure management. Imaging showed no evidence of acute stroke, but did show vasospasm in the occipital lobes. Vision improved over the next couple of months. CONCLUSION/CLINICAL RELEVANCE: This case illustrates a possible profound vasomotor phenomenon (cortical blindness) associated with AD and its symptomatic treatment. Early recognition of AD and treatment of its underlying cause cannot be overemphasized.

Isolated cranio-spinal involvement of Rosai-Dorfman disease: case report.

Rosai-Dorfman disease is a rare non-neoplastic lymphoproliferative condition. It commonly affects individuals between third and fifth decades, most common presentation being in the form of massive painless cervical lymphadenopathy with fever, weight loss and malaise. Isolated intracranial involvement is rare seen in less than 5% of patients with extranodal involvement. We present a patient with isolated contiguous cranio-spinal involvement who presented to us with remitting symptoms.

Degeneration of the Arnold's prefrontopontocerebellar tract in a case of locked-in syndrome over a 23-year period.

A 52-year-old woman has been under observation for a complete locked-in syndrome of vascular origin, since 1984. Her cognitive functions today are still normal. When first diagnosed, a CT-scan was made and 23 years later performed, a cerebral MRI was performed. A focal, bilateral and symmetric atrophy of the dorsomedial prefrontal gyri was clearly shown, contrasting with the non-atrophy of the precentral gyri (motor area), others prefrontal areas, frontopolar gyri and temporal cortices. Degeneration of the corticopontine projection, the first step in the corticopontocerebellar circuit, could explain this selective atrophy. This unique observation leads to the precise in vivo anatomical location of the Arnold tract.