Clinicopathologic Findings in Patients With Paraneoplastic Neuropathies and Antibodies Strongly Associated With Cancer.

BACKGROUND AND OBJECTIVES: Pathologic descriptions of peripheral nerve involvement in paraneoplastic neuropathies are sparse, mostly from autopsies focusing on CNS and dorsal root ganglia tissues. Here, we describe the clinicopathologic features of peripheral nerve biopsies in patients with paraneoplastic neurologic syndromes to expand the currently limited knowledge. METHODS: Retrospective review of the Mayo Clinic electronic medical record from 1995 to 2022 for patients identified to have subacute onset neuropathy with paraneoplastic antibodies identified in our neuroimmunology laboratory having available nerve biopsies performed at the time of diagnosis. Patients with another cause of neuropathy not linked to their subacute onset were excluded. RESULTS: Nineteen patients met inclusion criteria: 4 with amphiphysin antibodies, 6 with antineuronal nuclear antibody (ANNA)-1 only, 3 with both ANNA-1 and collapsin response-mediator protein 5 (CRMP-5), 2 with ANNA-2, and 4 with CRMP-5 antibodies only. Fifteen biopsies had reduced the density of myelinated nerve fibers-4 with multifocality. Subperineurial edema was present in 17 biopsies. Prominent epineurial perivascular inflammation was present in 3 biopsies, all belonging to patients with a lumbosacral radiculoplexus neuropathy (LRPN) phenotype. DISCUSSION: Axonal loss, subperineurial edema, and an absence of prominent inflammation are the most common findings in nerve biopsies of patients with paraneoplastic antibodies strongly associated with cancer. The LRPN phenotype was the only subset with inflammatory collections. Paraneoplastic autoantibody testing should be considered in patients with subacute onset neuropathies, with or without interstitial inflammatory findings.

Inherited myopathy plus: Double-trouble from rare neuromuscular disorders.

A rare disorder in the USA is one that affects <200,000 people, making inherited myopathies rare diseases. Increasing access to genetic testing has been instrumental for the diagnosis of inherited myopathies. Genetic findings, however, require clinical correlation due to variable phenotype, polygenic etiology of certain inherited disorders, and possible co-existing independent neuromuscular disorders. We searched the Mayo Clinic Rochester medical record (2004-2020) to identify adult patients carrying pathogenic variants or likely pathogenic variants in genes causative of myopathies and having a coexisting independent neuromuscular disorder classified as rare at https://rarediseases.info.nih.gov/. One additional patient was identified at Nationwide Children's hospital. Clinical and laboratory findings were reviewed. We identified 14 patients from 13 families fulfilling search criteria. Seven patients had a "double-trouble" inherited myopathy; two had an inherited myopathy with coexistent idiopathic myositis; three had an inherited myopathy with coexisting rare neuromuscular disorder of neurogenic type; a female DMD carrier had co-existing distal spinal muscular atrophy, which was featuring the clinical phenotype; and a patient with a MYH7 pathogenic variant had Sandhoff disease causing motor neuron disease. These cases highlight the relevance of correlating genetic findings, even when diagnostic, with clinical features, to allow precise diagnosis, optimal care, and accurate prognosis.

Immunotherapy for Peripheral Nerve Disorders.

Inflammatory peripheral neuropathies can be disabling for any patient. Selecting the most appropriate agent for treatment, especially in the elderly, is no simple task. Several factors should be considered. Herein, we discuss immunotherapeutic options for peripheral nerve diseases and the important considerations required for choosing one in the geriatric population.

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19.

BACKGROUND: Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. METHODS: We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. RESULTS: Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001). CONCLUSIONS: TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

OBJECTIVE: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes. METHODS: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders. RESULTS: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, p < 0.001). CONCLUSIONS: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Hypertrophic Olivary Degeneration and Movement Disorder in a Patient with Familial Creutzfeldt-Jakob Disease.

A 38-year-old male presented with a three-week history of bilateral lower extremity choreiform movements. History included sleep abnormalities, rushed and unintelligible speech, with delusions two to six months prior to presentation. He also developed mild dysphagia, staring spells, and anterograde amnesia. On examination, he had pressured speech, asynchronous cycling movements of the bilateral lower extremities persisting during sleep, occasional ballistic movements of the upper extremities, and ataxia. Magnetic resonance imaging (MRI) of the brain showed high cortical signal change in bilateral parieto-occipital cortices with evidence of medullary olive hypertrophy bilaterally. Electroencephalography showed generalized slowing without periodic spikes. Cerebrospinal fluid was positive for protein 14-3-3 and real-time quaking-induced conversion. Genetic testing was positive for autosomal dominant prion protein gene (PRNP) genetic mutation. The patient passed away three months after discharge. This case provides previously undescribed imaging and movement abnormalities in a patient with familial Creutzfeldt-Jakob disease (CJD), and suggests that CJD should not be removed from the differential in patients with these atypical findings.

Anterolateral Triangle: A Cadaveric Study with Neurosurgical Significance.

The anterolateral triangle is one of 10 surgical triangles of the cavernous sinus and serves as an important anatomic landmark for the skull base surgeon. There are few studies in the English literature that have precisely defined and measured the borders of the anterolateral triangle and little agreement has been made regarding the nomenclature within the English literature. A total of 12 midsagittally hemisected adult human cadaveric head halves were dissected to expose the anterolateral triangle. The triangle was defined and measurements of the anterior, posterior, and lateral borders were taken. The mean lengths and standard deviations of the anterior, posterior, and lateral borders were 8.3 ± 2.2 mm, 5.9 ± 2.0 mm, and 11.5 ± 2.9 mm, respectively. The mean area and standard deviation were 20.46 ± 9.30 mm2. The anterolateral triangle is helpful in understanding and planning surgical approaches to the cavernous sinus and middle cranial fossa. As such, normal anatomic relationships and the sizes of the anterolateral triangle must first be recognized to better access the pathologic changes within and around this region.

The anatomy of free fibula osteoseptocutaneous flap in neophalloplasty in transgender surgery.

The Free Fibula Osteoseptocutaneous flap is a reliable option when used in neophalloplastic procedures. It possesses intrinsic rigidity that is sufficient for penetrative intercourse, and satisfactory sensation. We review the pros and cons of this procedure, as well the anatomy and surgical steps involved. Surgical text descriptions were enhanced by the creation of new anatomic illustrations. Anatomy of the donor and recipient sites, as well as the surgical technique leading to creation of the neophallus are demonstrated in detail with new relevant illustrations. The free fibula osteoseptocutaneous flap provides the neophallus with many desirable characteristics. Its thick subcutaneous and fascial layer, along with the thicker fibula (compared to the radius), allows for a neophallus of greater diameter. Skin marking, flap lifting, and transfer to the perineum with all relevant neurovascular anastomosis; fibular artery is anastomosed with the femoral artery, while the fibular veins are anastomosed to branches of the saphenous vein, as well as neurorrhaphy of the dorsal nerves of the clitoris and the LSCN are demonstrated. The osteomatized fibula is fixed to the periosteum of the pubic symphysis as shown. Anatomical traits of the Free Fibula Osteoseptocutaneous flap allow intercourse without prosthesis. The donor-site scar in this procedure can be covered by a long sock, and donor site morbidity is acceptable. Clin. Anat. 31:169-174, 2018. © 2018 Wiley Periodicals, Inc.

Intracranial Anatomical Triangles: A Comprehensive Illustrated Review.

There are multiple anatomical triangles of the skull base. However, to our knowledge, there has been no comprehensive review of these geometric landmarks. To allow for a safe and consistent approach to lesions of the skull base such as those near the internal carotid artery, internal acoustic meatus, and cavernous sinus, a comprehensive review of the variations with illustrations is required. This article provides an overview of the anatomical borders, dimensions, and surgical implications as well as illustrations of the major skull base triangles.

Osborne's Ligament: A Review of its History, Anatomy, and Surgical Importance.

When discussing the pathophysiology of ulnar neuropathy, Geoffrey Vaughan Osborne described a fibrous band that can be responsible for the symptoms seen in this disorder. In this paper, we take a glimpse at the life of Osborne and review the anatomy and surgical significance of Osborne's ligament. This band of tissue connects the two heads of the flexor carpi ulnaris and thus forms the roof of the cubital tunnel. To our knowledge, no prior publication has reviewed the history of this ligament, and very few authors have studied its anatomy in any detail. Therefore, the aim of the present paper is to elucidate this structure that is often implicated and surgically transected to decompress the ulnar nerve at the elbow.

Mapping the Internal Anatomy of the Lateral Brainstem: Anatomical Study with Application to Far Lateral Approaches to Intrinsic Brainstem Tumors.

INTRODUCTION: Intramedullary brainstem tumors present a special challenge to the neurosurgeon. Unfortunately, there is no ideal part of the brainstem to incise for approaches to such pathology. Therefore, the present study was performed to identify what incisions on the lateral brainstem would result in the least amount of damage to eloquent tracts and nuclei. Case illustrations are also discussed. MATERIALS AND METHODS: Eight human brainstems were evaluated. Based on dissections and the use of standard atlases of brainstem anatomy, the most important deeper brainstem structures were mapped to the surface of the lateral brainstem. RESULTS: With these data, we defined superior acute and inferior obtuse corridors for surgical entrance into the lateral brainstem that would minimize injury to deeper tracts and nuclei, the damage to which would result in significant morbidity. CONCLUSIONS: To our knowledge, a superficial map of the lateral brainstem for identifying deeper lying and clinically significant nuclei and tracts has not previously been available. Such data might decrease patient morbidity following biopsy or tumor removal or aspiration of brainstem hemorrhage. Additionally, this information can be coupled with the previous literature on approaches into the fourth ventricular floor for more complex, multidimensional lesions.

The Vertebral Artery Cave at C2: Anatomic Study with Application to C2 Pedicle Screw Placement.

OBJECTIVE: Knowledge of the course of the vertebral artery during instrumentation is of paramount importance. It has been shown that erosion of the C2 pedicle and body can occur due to pulsations of the adjacent vertebral artery. This often results in a "cave" for this segment of the artery. The descriptions of this anatomy are limited. The current study was performed with the hope that these data will be of use to spine surgeons during C2 instrumentation. METHODS: In 40 human adult C2 bone specimens, the position of the vertebral artery in relation to the undersurface of the superior articular facet, pedicle, and C2 body was observed. A classification system was used to better describe these relationships. Pedicle screws were then placed into selected examples of each type. RESULTS: We found type 0 specimens, with no cave, on 8 sides (10%). Types I, II, and III caves with minimal, moderate, and significant encroachment of the pedicle were observed on 40%, 35%, and 27.5% sides, respectively. Type IV caves with erosion into the lateral C2 body and undersurface of the superior articular facet were observed on 12.5% of sides. Although larger caves were found on left sides, this did not reach statistical significance. Pedicle screw placement for types III and IV were most likely to enter the vertebral artery cave (P < 0.05). CONCLUSIONS: Additional osteologic data regarding the course of the vertebral artery while within C2 may decrease morbidity during surgery in this region.

Anatomy of turner syndrome.

Turner syndrome (TS) is one of the most common sex chromosome abnormalities and results from total or partial monosomy of the X chromosome. It occurs in 1 in 2000 newborn girls and is also believed to be present in a larger proportion of conceptuses. There are various anatomic anomalies that have been associated with TS and the consequences of late recognition of these anomalies can be devastating. Aortic dilation and dissection occur at increased rates in TS patients and contribute to the decreased life expectancy of these patients. Such cases have prompted the need for early identification and continuous monitoring. Other anatomic variations increase morbidity in this population, and negatively impact the social and reproductive aspects of their lives. In this review, we summarize the cardiovascular, neurological, genitourinary, otolaryngolical, craniofacial, and skeletal defects associated with TS. To elucidate these morphological variations, novel illustrations have also been constructed. Clin. Anat. 29:638-642, 2016. © 2016 Wiley Periodicals, Inc.