Outcomes after intervention for enteral nutrition in patients with amyotrophic lateral sclerosis in multidisciplinary clinics.

INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) are susceptible to malnutrition, with appropriate management of nutritional interventions an active area of investigation. We sought to determine the impact of gastrostomy tube placement in ALS patients, exploring the correlation between forced vital capacity (FVC), malnutrition, and perioperative complications. METHODS: A retrospective review was performed of clinically diagnosed ALS patients treated at two multidisciplinary clinics (University of Kansas, University of Nebraska) from January 2009 to September 2020 who were referred for gastrostomy. Data collected included demographics, disease characteristics, and key gastrostomy related dates/outcomes. RESULTS: Two hundred thirty-nine patients were included with a median age of 65 years and median of 589 days from symptom onset to gastrostomy (interquartile range, 404-943). The population was predominantly Non-Hispanic White with bulbar-onset ALS. 30-day mortality was 4% and 30-day morbidity was 13%. Weight loss, body mass index, and predicted FVC at placement showed no increased 30-day morbidity or mortality association. Bulbar-onset ALS patients exhibited higher overall mortality postplacement than limb onset (odds ratio: 1.85, 95% confidence interval: 1.03-3.33). There was a 5% incidence of symptoms suggestive of refeeding syndrome. DISCUSSION: Rates of major/minor complications and 30-day mortality related to gastrostomy placement in our population were similar compared with prior studies in ALS. The lack of difference in outcomes based on FVC at procedure may suggest this is not predictive of outcome, or perhaps, high-quality perioperative respiratory management. Alternative reasons may account for the increased morbidity and mortality of gastrostomy placement in the ALS population.

Acute and Chronic Demyelinating Neuropathies After COVID-19 Vaccination: A Report of 4 Cases.

OBJECTIVES: To report demyelinating neuropathies after COVID-19 vaccination. METHODS: Case report. RESULTS: Four cases of demyelinating neuropathies after COVID-19 vaccination were identified at the University of Nebraska Medical Center from May to September 2021. Three were male and 1 was a female, ages 26-64 years. Three cases received Pfizer-BioNTech vaccine and 1 Johnson & Johnson. Symptom onset ranged from 2 to 21 days after vaccination. Two cases had progressive limb weakness, 3 had facial diplegia, and all had sensory symptoms and areflexia. The diagnosis was acute inflammatory demyelinating polyneuropathy in 1 case and chronic inflammatory demyelinating polyradiculoneuropathy in 3. All cases received treatment with intravenous immunoglobulin, with significant improvement in 3 of 4 who had a long-term outpatient follow-up. CONCLUSIONS: Continued identification and reporting of cases of demyelinating neuropathies after COVID-19 vaccination is essential to determine whether a causative association is present.

Nitrofurantoin and Minocycline-Associated Vasculitic Neuropathy: Case Reports and Literature Review.

BACKGROUND: Vasculitic neuropathies usually present acutely to subacutely, with an asymmetric pattern, involving multiple peripheral nerve territories. Drug-induced vasculitis is an often overlooked etiology of vasculitic neuropathy. METHODS: We present the first reported case of nitrofurantoin-associated and an illustrative case of minocycline-associated vasculitic neuropathy, with a review of the literature. RESULTS: The first patient is a 60-year-old woman who developed axonal sensorimotor peripheral neuropathy after nitrofurantoin use, with a superficial radial nerve biopsy confirming vasculitis. The second patient is a 23-year-old woman, with a history of acne vulgaris treated with minocycline, who presented with a subacute right common peroneal mononeuropathy followed by a left deep peroneal mononeuropathy, with elevated antinuclear, perinuclear-antineutrophil cytoplasmic, and myleoperoxidase antibodies, and MPO titers, and a sural nerve biopsy showing large arteriole vasculitis. Finally, we provide a comprehensive review of previously published cases. CONCLUSIONS: Medications should be considered as a trigger for medication-induced vasculitic neuropathy. Accurate diagnosis would ensure timely treatment.

Anti-Neurofascin Antibodies Associated with White Matter Diseases of the Central Nervous System: A Red Flag or a Red Herring?

Autoantibodies against nodal and paranodal proteins, specifically anti-neurofascin antibodies (ANFAs), have been recently described in central and peripheral nervous system demyelinating disorders. We retrospectively reviewed the charts of six individuals evaluated at our Multiple Sclerosis Program who tested positive for serum ANFAs on Western blot. We describe these patients' clinical and diagnostic findings and attempt to identify features that might guide clinicians in checking for ANFAs. In our series, the women-to-men ratio was 2:1. At presentation, the median age was 60 years (range 30-70). The clinical presentation was pleiotropic and included incomplete transverse myelitis (n = 3), progressive myelopathy (n = 1), recurrent symmetric polyneuropathy (n = 1), and nonspecific neurological symptoms (n = 1). Atypical features prompting further workup included coexisting upper and lower motor neuron features, older age at presentation with active disease, atypical spinal cord MRI features, and unusual cerebrospinal fluid findings. The serum ANFAs panel was positive for the NF-155 isoform in five patients (IgM n = 2; IgG n = 2; both n = 1) and the NF-140 isoform in two (IgG n = 2). Larger studies are needed to assess the relevance of ANFAs in demyelinating nervous system diseases, their impact on long-term clinical outcomes, and associated therapeutic implications.

Acute Bulbar Palsy-Plus Variant of Guillain-Barré Syndrome in a 3-Year-Old Girl.

We present a case of a 3-year-old girl who rapidly developed bilateral facial palsy, dysphagia, dysphonia, areflexia, and ataxia soon after receiving an influenza vaccine. Brain and spine Magnetic resonance imaging (MRI) scans with and without contrast showed enhancement of cranial nerves III, V, VII, and X, as well as the anterior and posterior cervical spinal and cauda equina roots. cerebrospinal fluid (CSF) studies showed white blood cell count of 19 cells/cm2, glucose 81 mg/dL, and protein 116 mg/dL, with negative infectious and autoimmune labs. Serum IgM and IgG antibodies against GM1, GD1a, GD1b, GM2, GT1A, GQ1b were negative. The patient was treated with intravenous immunoglobulin, which led to a full recovery. Upon three-month follow-up, her neurologic examination demonstrated normal cranial nerves, reflexes, and gait. Her presentation was most consistent with the acute bulbar palsy plus (ABPp) variant of Guillain-Barré syndrome (GBS), a rare and challenging diagnosis especially in her age group.

Guillain Barre Syndrome as a Complication of COVID-19: A Systematic Review.

BACKGROUND: In January 2020, the first case of Guillain Barre syndrome (GBS) due to COVID-19 was documented in China. GBS is known to be postinfectious following several types of infections. Although causality can only be proven through large epidemiological studies, we intended to study this association by a thorough review of the literature. METHODS: We searched PubMed, EMBASE, and Google scholar and included all papers with English or Spanish full text and original data of patients with GBS and recent COVID infection. Variables of interest were demographics, diagnostic investigations, and the latency between arboviral and neurological symptoms. Further variables were pooled to identify GBS clinical and electrophysiological variants, used treatments, and outcomes. The certainty of GBS diagnosis was verified using Brighton criteria. RESULTS: We identified a total of 109 GBS cases. Ninety-nine cases had confirmed COVID-19 infection with an average age of 56.07 years. The average latency period between the arboviral symptoms and neurologic manifestations for confirmed COVID-19 cases was 12.2 d. The predominant GBS clinical and electromyography variants were the classical sensorimotor GBS and acute demyelinating polyneuropathy respectively. Forty cases required intensive care, 33 cases required mechanical ventilation, and 6 cases were complicated by death. CONCLUSIONS: Studies on COVID-19-related GBS commonly reported sensorimotor demyelinating GBS with frequent facial palsy. The time between the onset of infectious and neurological symptoms suggests a postinfectious mechanism. Early diagnosis of GBS in COVID-19 patients is important as it might be associated with a severe disease course requiring intensive care and mechanical ventilation.

Transthyretin Amyloidosis Presenting With Upper-Extremity Neuropathy and Paucity of Autonomic Impairment.

We report a 73-year-old man with Val142Ile transthyretin (TTR) amyloidosis and an atypical clinical presentation of upper-extremity-predominant neuropathy without significant autonomic or cardiac involvement. TTR familial amyloid polyneuropathy commonly presents as length-dependent sensorimotor polyneuropathy with marked and early autonomic involvement. Multiple pathogenic mutations in TTR gene have been identified, of which Val50Met is commonly associated with TTR familial amyloid polyneuropathy, and Val142Ile is commonly associated with familial amyloid cardiomyopathy. Our patient is from a nonendemic region, without family history for amyloidosis. Predominant upper-extremity neuropathy, without significant cardiac or autonomic involvement, distinguishes this case from previously reported Val142Ile-mutated TTR amyloidosis.

Inflammatory Diabetic Neuropathy: Helpful Diagnostic Parameters.

OBJECTIVES: Mild inflammatory diabetic neuropathies (IDNs) overlap with diabetic sensorimotor neuropathy (DPN) in clinical presentation and electrophysiological and laboratory tests. This study is to determine whether IDN can be differentiated from DPN by clinical features, electrophysiological, pathological, or laboratory tests. METHODS: Suspected IDN cases were identified by a subacute onset and progressive sensory or motor neuropathy in patients with diabetes. RESULTS: IDN occurred earlier in the course of diabetes mellitus and had higher prevalence of limb weakness, walking difficulty, and more severe electrophysiological abnormalities suggesting both demyelination and axonal loss. Sensory nerve biopsies in IDN showed perivascular inflammatory infiltrates, decreased fiber density, increased demyelination, and axonal degeneration. Most patients with IDN improved with immunotherapy. CONCLUSIONS: Features that favor IDN over DPN are limb weakness, more severe nerve conduction abnormalities, inflammatory infiltrates on nerve biopsy, and a favorable response to immunotherapy. A nerve biopsy can help establish an inflammatory cause.

Magnetic resonance imaging of the spinal cord in the evaluation of 3 patients with sensory neuronopathies: Diagnostic assessment, indications of treatment response, and impact of autoimmunity: A case report.

RATIONALE: Sensory neuronopathy can be a devastating peripheral nervous system disorder. Profound loss in joint position is associated with sensory ataxia, and reflects degeneration of large-sized dorsal root ganglia. Prompt recognition of sensory neuronopathies may constitute a therapeutic window to intervene before there are irreversible deficits. However, nerve-conduction studies may be unrevealing early in the disease course. In such cases, the appearance of dorsal column lesions on spinal-cord MRI can help in the diagnosis. However, most studies have not defined whether such dorsal column lesions may occur within earlier as well as chronic stages of sensory neuronopathies, and whether serial MRI studies can be used to help assess treatment efficacy. In this case-series of three sensory neuronopathy patients, we report clinical characteristics, immunological markers, nerve-conduction and skin-biopsy studies, and neuroimaging features. PATIENT CONCERNS: All three patients presented with characteristic features of sensory neuronopathy with abnormal spinal-cord MRI studies. Radiographic findings included non-enhancing lesions in the dorsal columns that were longitudinally extensive (spanning ≥ 3 vertebral segments). DIAGNOSES: All patients had anti-Ro/SS-A and/or anti-La/SS-B antibodies, with patients one and two having Sjögren's syndrome. MRI findings were similar when performed in the earlier stages of a sensory neuronopathy (patient one, after four months) and chronic stages (patients two and three, after five and three years, respectively). INTERVENTIONS: Patient one was treated with rituximab combined with intravenous immunoglobulin therapy. OUTCOMES: Patient one was initially wheelchair-bound and had improved ambulation after treatment. In this patient, serial MRI studies revealed partial resolution of dorsal column lesions, associated with decreased sensory ataxia and improved nerve-conduction studies. LESSONS: In addition to vitamin B12 and copper deficiency, it is important to include sensory neuronopathies in the differential diagnosis of dorsal column lesions. MRI spinal-cord lesions have similar appearances in the earlier as well as chronic phases of a sensory neuronopathy, and therefore suggest that such dorsal column lesions may reflect inflammatory as well as a gliotic burden of injury. MRI may also be a useful longitudinal indicator of treatment response.

Nerve pathologic features differentiate POEMS syndrome from CIDP.

The objective of this study is to determine if the nerve pathology in patients with POEMS syndrome is different from CIDP. We hypothesized that nerve biopsies from patients with POEMS syndrome would have more small vessels and axonal degeneration but less inflammation than CIDP.We performed a retrospective analysis of nerve biopsies performed on "classic" CIDP and POEMS cases. Nerve biopsies were blinded and reviewed by two of the authors (EAP, PJBD). Teased fibers, paraffin-embedded sections, semithin sections and immunostains were analyzed. Small endoneurial and epineurial vessels were counted on paraffin sections with smooth muscle actin (SMACTIN) preparation to judge for neovascularization.A total of 61 cases (35-POEMS, 26-CIDP) were included. The POEMS-group had significantly higher axonal degeneration and fewer normal myelinated fibers on teased fiber preparations. The CIDP-group had significantly more endoneurial mononuclear inflammation on paraffin sections and immunostains. Large onion-bulbs were present only in CIDP cases. A significantly higher number of epineurial vessels was present in POEMS biopsies, with a total count of 120 epineurial vessels predicted as best cutoff to differentiate both conditions (77 % specific and 54 % sensitive).In conclusion, nerve biopsy can be helpful in distinguishing POEMS syndrome from CIDP. POEMS syndrome demonstrates more axonal degeneration and epineurial neovascularization whereas CIDP has greater endoneurial inflammation and onion-bulb formation. These findings support the idea that there are differing underlying mechanisms for these disorders, POEMS being related to paraneoplastic vasculopathy associated with angiogenic factors and CIDP related to inflammatory demyelination.

Autonomic system and amyotrophic lateral sclerosis.

INTRODUCTION: The aim of this study is to characterize autonomic impairment in motor neuron disease. METHODS: Neurological evaluations and autonomic testing were analyzed retrospectively in 132 patients: 86 classic amyotrophic lateral sclerosis (ALS), 36 lower motor neuron (LMN), and 10 upper motor neuron (UMN) predominant disease. RESULTS: One-third of patients were symptomatic; urinary urgency and constipation were the most frequent symptoms. Increased Composite Autonomic Severity Score (CASS) was present in 75% with mild impairment (CASS 1-3) in 85% and moderate (CASS 4-7) in 15%. The frequencies of testing abnormalities were: sudomotor 46%, cardiovagal 50%, and adrenergic 14%. The UMN group had significantly higher median CASS scores than the classic ALS (P = 0.021) and LMN group (P = 0.018). CONCLUSIONS: We found predominantly mild autonomic impairment in ALS patients, with mostly cardiovagal and sudomotor involvement. Moderate autonomic failure occurred in 1 of 7 patients, especially those with an UMN presentation. Patients with selective corticospinal tract involvement may have more impairment of autonomic pathways.

Las respuestas lentas a la angiotensina II, la activación de la proteína Src y del factor de crecimiento epidérmico en la génesis de la hipertensión esencial / Factors contributing to essential hypertension genesis

La hipertensión esencial es inducida por disfunción renal. Receptores normotensos de riñones de hipertensos desarrollan hipertensión y viceversa. La alteración renal más importante es el desacople del SRA respecto del nivel de sodio. El estrés oxidativo (ST-OX) es estimulado cuando los niveles de angiotensina II (Ang II) son inapropiados respecto del sodio corporal total. El ST-OX potencia el efecto vasoconstrictor de la Ang II por disminución del óxido nítrico (NO) y/o por incremento de los vasoconstrictores, como isoprostanos, ET1 y otros. Estos efectos se ponen de manifiesto en la ôrespuesta lenta a la Ang IIõ en la que la infusión en dosis pequeñas (subpresoras) induce retención de sodio y consecuente estímulo del STOX, con vasoconstricción. Estos efectos están mediados por señales intracelulares como la activación de proteína Src y del receptor del factor de crecimiento epidérmico por la Ang II, que parecen ser un mecanismo de vasoconstricción importante. Las especies reactivas de oxígeno inducidas por estos factores sostendrían una reacción autocatalítica, responsable de la producción sostenida de vasoconstrictores, con lo que se perpetúa la hipertensión.