Acute onset of chronic infl ammatory demyelinating polyneuropathy in combination with COVID-19

Acute onset of chronic infl ammatory demyelinating polyneuropathy (A-CIDP) presents signifi cant diffi culties in differential diagnosis with acute infl ammatory demyelinating polyneuropathy (AIDP). The article presents review of literature about diff erential diagnosis between A-CIDP and AIDP and a clinical case of A-CIDP at 26-year-old man. The disease started after vaccination against infl uenza and an episode of enteritis, the clinical picture matched Guillain–Barré syndrome criteria, according to electromyography data: demyelinating lesion of the left facial nerve, motor and sensory fi bers of the median and ulnar nerves on both sides, demyelinating lesions of motor fi bers of the tibial nerve and peroneal nerve on both sides. Chronic infl ammatory demyelinating polyneuropathy was diagnosed. Lack of eff ect from plasma exchange was the reason for changing the treatment to pulse therapy with prednisolone (with a subsequent transition to a 1 mg/kg dose and further reduction until canceled within 16 weeks). Response to prednisolone — rapid recovery of motor functions, which worsened signifi cantly due to a new coronavirus infection during treatment in the neurology department. Further continuation of prednisolone therapy made it possible to restore motor functions completely, except mild prosopoparesis. At the same time, deep refl exes were absent; no signifi cant EMG dynamics was observed. Considering the eff ect of glucocorticosteroids and lack of positive dynamics on the second electromyography, the patient was diagnosed as A-CIDP.

Durvalumab-Induced Demyelinating Lesions in a Patient With Extensive-Stage Small-Cell Lung Cancer: A Case Report

It is of great clinical value to investigate the immune-related adverse events (irAEs), especially demyelinating lesions, caused by immune checkpoint inhibitors (ICIs). The incidence of demyelinating lesions is less frequent in irAEs, but once it occurs, it will seriously affect the survival of patients. The present study reports a case of durvalumab-induced demyelinating lesions in a patient with extensive-stage small-cell lung cancer. Subsequently, the patient receives a high intravenous dose of methylprednisolone and his condition is improved after 21 days of treatment. Altogether, early diagnosis and treatment of ICIs-related neurological irAEs is of great significance to the outcome of the patient’s condition.

Cerebrospinal fluid evaluation in patients with progressive motor impairment due to critical central nervous system demyelinating lesions

Background Elevated intrathecal immunoglobulin G (IgG; oligoclonal bands (OCBs)) or IgG in people with progressive motor impairment due to “critical” demyelinating lesions are of uncertain significance. Objective Compare clinical/radiological features of people with “critical” demyelinating lesion-induced progressive motor impairment with/without elevated intrathecal IgG synthesis. Methods A total of 133 people with progressive motor impairment attributable to “critical” demyelinating lesions (corticospinal tract location, consistent with the progressive motor deficit) were compared regarding clinical and radiological presentation with and without ≥2 unique cerebrospinal fluid (CSF) OCB and/or IgG index ≥0.85. Results Ninety-eight (74%) had CSF-elevated OCB and/or IgG index, higher with increased magnetic resonance imaging-lesion burden. No differences were found with/without CSF abnormalities in sex (46 of 98 female (47%) vs. 22 of 35 (63%), p = 0.11), onset-age (median 49 vs. 50 years, p = 0.5), progression from onset (62 of 98 (63%) vs. 25 of 35 (71%)), progression post-relapse (36 of 98 (37%) vs. 10 of 35 (29%), p = 0.4), and duration between demyelinating disease onset and CSF examination (30 (0–359) vs. 48 (0–323) months p = 0.7). “Critical” lesions were radiologically similar, most commonly cervical spine located (72 of 98 (74%) vs. 19 of 35 (54%), p = 0.18) both with/without CSF abnormalities. Conclusions People with “critical” demyelinating lesion-induced progressive motor impairment typically have elevated intrathecal IgG (OCB and/or IgG) and similar clinical and radiological presentation regardless of CSF findings, therefore representing valid presentations of progressive demyelinating disease.

A Comparison of Magnetic Resonance Imaging Methods to Assess Multiple Sclerosis Lesions: Implications for Patient Characterization and Clinical Trial Design

Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue properties of the white matter hyperintensities using STAGE (strategically acquired gradient echo imaging). Additionally, the outcomes of this study were anticipated to aid in the choice of an efficient imaging protocol reducing redundancy of information and alleviating patient burden. Of all the sequences used, T2 FLAIR and T2WI showed the most lesions. To differentiate the putative demyelinating lesions from inflammatory lesions, the fusion of SWI and T2 FLAIR was used. Our study suggests that a practical and efficient imaging protocol combining T2 FLAIR, T1WI and STAGE (with SWI and QSM) can be used to rapidly image MS patients to both find lesions and study the demyelinating and inflammatory characteristics of the lesions.

The red flags of ulnar neuropathy in leprosy

The diagnosis of pure neural leprosy is more challenging because patients share characteristics with other common pathologies, such as ulnar compression, which should be taken into consideration for differential diagnosis. In this study, we identify ulnar nerve conduction characteristics to aid in the differential diagnosis of ulnar neuropathy (UN) in leprosy and that of non-leprosy etiology. In addition, we include putative markers to better understand the inflammatory process that may occur in the nerve. Data were extracted from a database of people affected by leprosy (leprosy group) diagnosed with UN at leprosy diagnosis. A non-leprosy group of patients diagnosed with mechanical neuropathy (compressive, traumatic) was also included. Both groups were submitted to clinical, neurological, neurophysiological and immunological studies. Nerve enlargement and sensory impairment were significantly higher in leprosy patients than in patients with compressive UN. Bilateral impairment was significantly higher in the leprosy group than in the non-leprosy group. Leprosy reactions were associated to focal demyelinating lesions at the elbow and to temporal dispersion (TD). Clinical signs such as sensory impairment, nerve enlargement and bilateral ulnar nerve injury associated with eletrodiagnostic criteria such as demyelinating finds, specifically temporal dispersion, could be tools to help us decided on the best conduct in patients with elbow ulnar neuropathy and specifically decide if we should perform a nerve biopsy for diagnosis of pure neural leprosy.

Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the central nervous system. Recently, the dysregulation of alternative splicing (AS) in the brain has been found to significantly influence the progression of MS. Moreover, previous studies demonstrate that many MS-related variants in the genome act as the important regulation factors of AS events and contribute to the pathogenesis of MS. However, by far, no genome-wide research about the effect of genomic variants on AS events in MS has been reported. Here, we first implemented a strategy to obtain genomic variant genotype and AS isoform average percentage spliced-in values from RNA-seq data of 142 individuals (51 MS patients and 91 controls). Then, combing the two sets of data, we performed a cis-splicing quantitative trait loci (sQTLs) analysis to identify the cis-acting loci and the affected differential AS events in MS and further explored the characteristics of these cis-sQTLs. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate gene interaction pattern and functions of the affected AS events in MS. In total, we identified 5835 variants affecting 672 differential AS events. The cis-sQTLs tend to be distributed in proximity of the gene transcription initiation site, and the intronic variants of them are more capable of regulating AS events. The retained intron AS events are more susceptible to influence of genome variants, and their functions are involved in protein kinase and phosphorylation modification. In summary, these findings provide an insight into the mechanism of MS.

Multiple Sclerosis and Cognitive Impairment

A 60-year-old woman with a history of multiple sclerosis was evaluated for cognitive concerns. At age 30 years she had an episode of optic neuritis, followed by an episode of bilateral lower extremity numbness at age 35 years. In the following years, she had at least 6 further multiple sclerosis relapses, the last one approximately 3 years before the current presentation. She was initially treated with interferon, but she did not tolerate it. She had been taking glatiramer acetate for the past 3 years. She had noticed progressive deterioration of her gait for the past 3 years, having to use a cane on occasions. Magnetic resonance imaging of the brain showed multiple demyelinating lesions), and magnetic resonance imaging of the cervical spine showed 1 small demyelinating lesion at C6. Vitamin B12 level and thyroid function were normal. Comprehensive neuropsychological testing showed multidomain cognitive impairment, mainly impairment of speed of information processing, spatial discrimination skills, and attention/concentration. The patient’s multiple sclerosis phenotype was consistent with secondary progressive multiple sclerosis. Her cognitive impairment profile, mainly affecting information processing speed and disinhibition suggestive of frontal dysfunction, was consistent with multiple sclerosis. The patient began a cognitive rehabilitation program, and learning and memory aids were recommended. Lifestyle changes were also recommended, including weight loss and physical exercise. She was given recommendations for sleep hygiene and began taking gabapentin for neuropathic pain and restless legs. Cognitive impairment is common in patients with multiple sclerosis. Slowed cognitive processing speed and episodic memory decline are the most common cognitive deficits in MS, with additional difficulties in executive function, verbal fluency, and visuospatial analysis.

Fluctuating Vision Loss, Seizures, and Left Parieto-Occipital Mass

A 35-year-old man sought care for progressive visual disturbance. Magnetic resonance imaging of the brain showed a large, left-sided, parieto-occipital, contrast-enhancing lesion. He was treated with dexamethasone with brief improvement in vision. Within 5 days he had progressive vision worsening. Two weeks after the onset of his symptoms, brain magnetic resonance imaging showed a decrease in lesion size, and corticosteroids were discontinued. Two months after symptom onset he was found to have alexia without agraphia, and follow-up magnetic resonance imaging showed an increased size of the lesion. Two months after disease onset, the patient underwent a left occipital brain biopsy, which demonstrated a macrophage-enriched active demyelinating lesion with relative axonal sparing. Right arm weakness and aphasia developed, along with a fever. He was treated with dexamethasone. Electroencephalography indicated multiple seizures. Repeated cerebrospinal fluid analysis showed a slightly increased white blood cell count, increased protein level, immunoglobulin G index of 0.84, and the presence of 3 cerebrospinal fluid-unique oligoclonal bands. He was treated with 5 days of intravenous methylprednisolone and levetiracetam, with improvement. Three and a half years later, the patient came to the emergency department with weakness of the left leg associated with reduced sensation. Spinal magnetic resonance imaging showed a new demyelinating contrast-enhancing lesion from T2 to T7. He was treated with 5 days of intravenous methylprednisolone followed by 6 sessions of plasma exchange, with improvement. A diagnosis of relapsing tumefactive demyelination was made. The patient was subsequently treated with ocrelizumab. Tumefactive demyelinating lesions pose a diagnostic challenge, especially if they are the first manifestations of demyelinating disease. Typically, tumefactive demyelinating lesions are large (>2 cm) and are associated with edema, mass effect, and variable patterns of contrast enhancement.

Progressive Left Lower Extremity Weakness and Thoracic Spinal Cord Lesion

A 76-year-old man was seen for a neurologic evaluation with concerns of progressive left lower extremity weakness. He had 2 lumbar spinal operations, the most recent being at age 68 years, and had a major motor vehicle accident with a pelvic fracture at age 67 years. He was documented to have new impairment in right ankle and distal lower extremity power after the operations and trauma. He began using a left-sided ankle-foot orthosis but used no other gait aid. Brain magnetic resonance imaging revealed 2 prominent and stable T2-signal hyperintensities in the frontal cerebral white matter, with some periventricular T2 hyperintensity with associated T1 hypointensity, and no gadolinium-enhancing lesions or posterior fossa lesions. Sagittal and axial magnetic resonance imaging of the thoracic spine showed an area of T2-signal abnormality without enhancement in the left hemicord at the T3 to T4 level. Nerve conduction studies and electromyography revealed a chronic right L5 radiculopathy without evidence of active denervation as the cause of the right lower motor neuron lower extremity weakness. He was diagnosed with progressive paucisclerotic multiple sclerosis with a primary progressive disease course. The use of ocrelizumab (anti-CD20) was considered initially. However, the exceedingly slow disease progression over many decades and the lack of new magnetic resonance imaging lesions or gadolinium-enhancing lesions, as well as his age, were taken into consideration, and conservative rehabilitation management was recommended instead. It is being increasingly recognized that the location of demyelinating disease lesions may be of crucial importance in the development of motor progression in multiple sclerosis. These critical demyelinating lesions are observed in patients with progressive unilateral hemiparetic impairment due to multiple sclerosis, in which unlimited lesion burden is allowable.

Case Report: Persisting Lymphopenia During Neuropsychiatric Tumefactive Multiple Sclerosis Rebound Upon Fingolimod Withdrawal

Fingolimod (FTY) is a disease modifying therapy for relapsing remitting multiple sclerosis (RRMS) which can lead to severe lymphopenia requiring therapy discontinuation in order to avoid adverse events. However, this can result in severe disease reactivation occasionally presenting with tumefactive demyelinating lesions (TDLs). TDLs, which are thought to originate from a massive re-entry of activated lymphocytes into the central nervous system, are larger than 2 cm in diameter and may feature mass effect, perifocal edema, and gadolinium enhancement. In these cases, it can be challenging to exclude important differential diagnoses for TDLs such as progressive multifocal leukoencephalopathy (PML) or other opportunistic infections. Here, we present the case of a 26-year-old female patient who suffered a massive rebound with TDLs following FTY discontinuation with primarily neuropsychiatric symptoms despite persisting lymphopenia. Two cycles of seven plasmaphereses each were necessary to achieve remission and ocrelizumab was used for long-term stabilization.