bluuebunny/crossref_metadata_2025 huggingface dataset:
Myelopathies
Authors: Kumar Shivram , Flemming Kelly D.
Published: November 2021

A myelopathy is a disorder of the spinal cord. The symptoms and signs of myelopathy can vary depending on which part of the spinal cord is affected and on the cause of the myelopathy. Certain causes of myelopathy tend to affect distinct areas of the spinal cord. The severity of myelopathies can vary even when the causes are identical. This chapter reviews the clinical features and evaluation of myelopathies in general and the specific forms of myelopathy.
Motor Neuron Diseases
Authors: Sorenson Eric J.
Published: November 2021

The motor neuron disorders are a clinically diverse group of diseases that share a pathologic loss of the motor neurons. The most common adult-onset disorder is amyotrophic lateral sclerosis (ALS). Other forms include the spinal muscular atrophies, infectious motor neuronopathies, and rare focal forms of anterior horn cell loss.Overall, the incidence rate of ALS is believed to be 1.5 to 2.0 cases per 100,000 person-years, and the prevalence rate is 4 to 6 cases per 100,000 population. Other than in sparsely populated geographic clusters (eg, Guam and the Kii Peninsula of Japan), the incidence rate seems consistent across ethnic and geographic boundaries.
Inherited Muscle Disorders
Authors: Liewluck Teerin , Milone Margherita
Published: November 2021

Inherited muscular disorders can manifest at any age, from prenatal life to adulthood. The broad differential diagnosis includes muscular dystrophies, congenital myopathies, disorders of glycogen and lipid metabolism, channelopathies, and mitochondrial disorders. Muscular dystrophies may present at any age, are inherited, and involve progressive degeneration of muscle, which is often replaced by connective tissue. Muscular dystrophies result from defects in the sarcolemmal proteins of muscle, including dystrophin-associated muscle membrane protein complex, muscle intracellular proteins (eg, nuclear envelope proteins), and extracellular matrix proteins (eg, collagen VI).
Neuro-ophthalmology: Disorders of Visual Perception, Pupils, and Eyelids
Authors: Kumar Shivram , Flemming Kelly D.
Published: November 2021

Visual loss may develop acutely, subacutely, or insidiously. The course may be transient, static, or progressive. This chapter reviews the causes, diagnosis, and treatment of various disorders resulting in visual loss or abnormal visual perception. In addition, it reviews clinical disorders of the eyelids and pupils. Disorders of visual perception involve visual acuity, color perception, visual field defects, and other visual changes. Historical information and physical findings on examination can help to localize the problem and define the cause.
Neuro-ophthalmology: Extraocular Muscles and Cranial Nerves III, IV, and VI
Authors: Brazis Paul W. , Flemming Kelly D.
Published: November 2021

Conjugate eye movement requires voluntary and reflexive input to the final common pathway (cranial nerves III, IV, and VI and their respective muscles). This chapter briefly repeats information about the pertinent anatomy of the extraocular muscles and cranial nerves III, IV, and VI but focuses on related clinical syndromes or diseases. Supranuclear input to these structures and dysfunction are discussed in other chapters. Six muscles move each eye globe: 4 recti (superior, inferior, medial, and lateral) and 2 oblique (superior and inferior) muscles.
Introduction and Approach to Headache
Authors: Halker Singh Rashmi B. , VanderPluym Juliana H.
Published: November 2021

Headache is experienced by 93% of men and 99% of women at some time in their lives. It is the most common complaint treated by neurologists and the seventh most common complaint treated by primary care providers. Although most headaches in the general population meet the criteria for tension-type headache, migraine is the most common headache treated in clinical practice and affects 18% of women and 6% of men, typically in their peak years of productivity. Evaluation of headache should include a thorough history and general, musculoskeletal, and neurologic examinations. Paramount in the headache evaluation is the proper identification of red flags that may indicate an underlying secondary cause of headache.
Nonglial Central Nervous System Tumors
Authors: Sharma Akanksha , Porter Alyx B.
Published: November 2021

Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that may involve the brain, leptomeninges, eyes, or spinal cord and accounts for up to 5% of all adult primary brain neoplasms. Age-adjusted incidence has increased in the past 3 decades. Infection with HIV and acquired immunodeficiency syndrome increase the risk of PCNSL by 3,600-fold. However, with highly active antiretroviral therapy, the frequency of immune system compromise sufficient for HIV-associated PCNSL (CD4 count ≤50) is dramatically reduced, along with the risk of this disorder.
Spinal Cord Tumors
Authors: Carabenciov I. Darin , Uhm Joon H.
Published: November 2021

Spinal tumors can be broadly classified on the basis of the anatomical compartment they occupy. These tumors can be intramedullary, intradural extramedullary, or extradural. Regardless of location, significant neurologic morbidity can occur as a result of their effects on the spinal cord or the cauda equina, or both. This chapter summarizes the pathophysiologic factors, clinical characteristics, imaging characteristics, and treatment of each tumor type.
DNA and RNA Viral Infections of the Nervous System
Authors: Toledano Michel , Aksamit Jr Allen J.
Published: November 2021

Viruses may cause acute, subacute, or, rarely, chronic infection of the nervous system. The most common acute syndromes of nervous system infections are meningitis and encephalitis, but viruses can also affect the spinal cord and the peripheral nervous system. Viruses can be classified in many ways. One classification scheme assesses the type of nucleic acid (DNA or RNA), whether it is double or single stranded, its sense, and its method of replication.
Fungal Infections of the Central Nervous System
Authors: Wilson John W.
Published: November 2021

Fungal infections within the central nervous system (CNS) occur more commonly in patients with immunosuppressive conditions but occasionally are diagnosed in immunocompetent patients as well. This may reflect the route of infection and the specific pathogen. Fungal infections resulting from hematogenous seeding are typically encountered in patients with profound and prolonged immunosuppression (including neutropenia); however, pathogens such as Cryptococcus gattii and some dimorphic fungi can also produce CNS disease in otherwise healthy persons. A common avenue of infection in immunocompetent patients is traumatic or nosocomial inoculation, including neurosurgical procedures, foreign body implants, and contaminated spinal fluid injections.
Prion Disorders: Creutzfeldt-Jakob Disease and Related Disorders
Authors: Cutsforth-Gregory Jeremy K.
Published: November 2021

Prion disorders, or transmissible spongiform encephalopathies (TSEs), are universally fatal human and animal diseases that cause rapid degeneration of brain neurons by way of a conformational change in the prion protein that autocatalyzes further conformational change and selective neuronal toxicity. TSEs may occur sporadically, be inherited, or, least frequently, spread like an infectious agent. Mounting evidence suggests that degenerative proteinopathies such as Alzheimer disease and Parkinson disease may also involve prionlike spread of abnormal proteins between neurons but not between organisms as in the prion disorders discussed in this chapter.
Malformation of the Brain, Skull, and Spine
Authors: Wong-Kisiel Lily C.
Published: November 2021

Abnormal development of the central nervous system is a common cause of developmental delay and epilepsy. An understanding of central nervous system malformation begins with an overview of normal embryology. Genetic advances in embryogenesis have unfolded a complex orchestration of gene expressions in place of the traditional developmental epochs (induction, neurulation, proliferation, migration, organization, synaptogenesis, and myelination). Causes of malformation of the central nervous system are multifactorial. Genetic causes, vitamin excess or deficiency, infections, or teratogens any time during pregnancy may disturb the preprogrammed mechanisms.
Neurodevelopmental Disabilities
Authors: Nickels Katherine C.
Published: November 2021

An understanding of developmental disabilities requires a good understanding of normal childhood development. Developmental milestones are typically divided into different domains, such as gross motor, fine motor, language, and social/adaptive skills. Assessment of attained milestones across the developmental domains allows the examiner to evaluate potential cognitive outcome. Emotional development is also important at all ages.
Neurometabolic Disorders Associated With Disturbances of Small Molecule Metabolism
Authors: Renaud Deborah L.
Published: November 2021

Inborn errors of metabolism affect approximately 1 in 1,000 to 1 in 3,000 live births. Most of these inherited conditions are autosomal recessive, although a few are autosomal dominant or X-linked. Mitochondrial DNA disorders may be maternally inherited. The clinical symptoms associated with inborn errors of metabolism reflect the disruption of normal biochemical processes required for synthesis, breakdown, or transport of metabolites. This impairment leads to accumulation of metabolites that cause toxic effects, inadequate levels of metabolites required for normal cellular activity, or secondary disruption of essential metabolic pathways. Small molecule disorders involve the metabolism of amino acids, organic acids, carbohydrates, fatty acids, and other biochemical pathways. These disorders may present with acute exacerbations superimposed on long-term neurologic symptoms.
Inherited Leukoencephalopathies
Authors: Renaud Deborah L.
Published: November 2021

Leukoencephalopathies are disorders that selectively involve the white matter of the brain. Acquired causes of leukoencephalopathy include inflammatory, infectious, vascular, neoplastic, and toxic disorders. Hereditary leukoencephalopathies encompass conditions characterized by progressive destruction or loss of previously acquired central myelin (leukodystrophies) and conditions associated with impaired formation of myelin (dysmyelination or hypomyelination). The study of clinical features, neuroimaging patterns, and biochemical and neuropathologic features of leukoencephalopathies has led to the discovery of the genetic defects responsible for many of these conditions. Variations in phenotype-genotype correlation can make prediction of the underlying condition challenging. Despite recent advances in molecular studies, approximately 50% of patients with hereditary leukoencephalopathies remain without a diagnosis. A systematic approach to guide investigations is important for a diagnosis.
Electrolyte Disturbances and Acid-Base Imbalance
Authors: Hocker Sara E. , Daneshmand Ali
Published: November 2021

Electrolyte disorders are among the most common clinical problems encountered in critically ill patients. Disorders such as severe burns, trauma, sepsis, acute brain injury, and heart failure lead to disturbances in fluid and electrolyte homeostasis through complex mechanisms involving deregulation or activation of hormonal systems and ischemic or nephrotoxic kidney injury. Inappropriate fluid management should also be considered in the differential diagnosis of electrolyte disturbances in patients in intensive care units. Electrolyte imbalances produce both central and peripheral neurologic dysfunction because electrochemical membrane potentials in brain, nerve, and muscle tissues are particularly sensitive to chemical, ionic, and osmolar shifts.
Neurologic Manifestations of Endocrine Diseases
Authors: Kumar Shivram , Flemming Kelly D.
Published: November 2021

The endocrine system is involved in creating and distributing hormones that have wide-ranging organ effects and a potential for neurologic complications. Neurologic manifestations related to dysfunction of the thyroid, parathyroid, and adrenal glands are discussed in the present chapter. The pituitary gland is subdivided into anterior and posterior lobes. The anterior pituitary (the adenohypophysis) synthesizes follicle-stimulating hormone and luteinizing hormone (which are important in the male and female hypothalamic-gonadal axes); growth hormone; corticotropin (also known as adrenocorticotropic hormone, which stimulates cortisol secretion from the adrenal glands); thyrotropin (also known as thyroid-stimulating hormone, which stimulates secretion of thyroid hormone from the thyroid gland); and prolactin.
Toxins and Environmental Neurologic Injury
Authors: Hocker Sara E. , Daneshmand Ali
Published: November 2021

Toxins and environmental exposures may result in central or peripheral nerve dysfunction. Toxins may be purposely ingested (eg, substance misuse), or exposure may be accidental (eg, occupational exposure or terrorism). Certain environmental exposures (eg, lightning or high altitude) may also result in neurologic injury. This chapter reviews neurologic clinical syndromes associated with toxins and the physical effects of certain environmental conditions.
Polysomnography and Other Sleep Testing
Authors: Castillo Pablo R.
Published: November 2021

Multiple methods are available for evaluating sleep concerns: clinical screening instruments, sleep diaries, polysomnography with multiple sleep latency test and maintenance of wakefulness test, and actigraphy. This chapter reviews the tools used to assess patients with sleep concerns. Screening tools such as questionnaires are used to stratify patients on the basis of their clinical characteristics and risk factors for sleep difficulties. Patients at high risk may need urgent polysomnography or further treatment.
Circadian Disorders, Insomnia, and Parasomnias
Authors: Dredla Brynn K. , Arunthari Vichaya
Published: November 2021

Circadian rhythm disorders have misalignment between the desired sleep schedule and the circadian (24-hour) sleep-wake rhythm. Many persons experience this misalignment with jet lag. Other common circadian rhythm disorders include delayed sleep-phase disorder, advanced sleep-phase disorder, and shift-work sleep disorder. Insomnia is one of the most common medical concerns, and its prevalence increases with age. Patients may have difficulty initiating sleep or maintaining sleep and generally have a poor quality of sleep. Causes of insomnia are multifactorial.
Progressive Left Lower Extremity Weakness and Thoracic Spinal Cord Lesion
Authors: Keegan B. Mark
Published: November 2021

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.
Fluctuating Vision Loss, Seizures, and Left Parieto-Occipital Mass
Authors: Kalinowska-Lyszczarz Alicja , Tobin W. Oliver , Guo Yong , Lucchinetti Claudia F.
Published: November 2021

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.
Diffuse Pain and Abnormal Brain MRI Findings
Authors: McKeon Andrew
Published: November 2021

A 46-year-old woman with a remote history of classical migraine had development of pain behind her left eye followed by holocephalic headache. She subsequently began to have episodic headaches. Her sleep became disrupted. Irritability, cognitive symptoms, and fatigue then developed. Her headaches occurred daily, along with whole-body discomfort. She underwent polysomnography and was diagnosed with obstructive sleep apnea syndrome. Her sleep quality improved with continuous positive airway pressure therapy, but her daily headaches, cognitive symptoms, and limb pain persisted. She was diagnosed with “seronegative Lyme disease.” Fourteen days of doxycycline therapy was not accompanied by improvement in symptoms. After extensive laboratory evaluations and consultations, the patient was diagnosed with fibromyalgia. Short trials of low doses of amitriptyline, nortriptyline, gabapentin, and pregabalin were undertaken, but these were poorly tolerated and discontinued in each instance. The patient was concerned that she may have multiple sclerosis, and she underwent magnetic resonance imaging of the brain. The radiology report documented multiple, small areas of T2-signal change, and demyelinating disease was included in the radiologic differential diagnosis. The patient then sought a second opinion. Evaluations at Mayo Clinic supported evidence of diffuse myofascial limb and back pain and tenderness. Brain magnetic resonance images were reviewed. Extensive work-up for alternative differential diagnostic considerations for her pain was unremarkable. The patient was diagnosed with fibromyalgia with features of central sensitization, with brain magnetic resonance imaging demonstrating nonspecific radiologic abnormalities. A detailed discussion about fibromyalgia and central sensitization was undertaken with the patient. The concepts rehabilitative approaches were reviewed. Slowly progressive, incremental, physical reconditioning, and cognitive behavioral retraining were recommended. She was advised to complete a fibromyalgia and chronic fatigue treatment program, focusing on cognitive and behavioral approaches, stress management, sleep hygiene, balanced lifestyle, moderation, energy conservation, and graded exercise. No new medications were recommended given her previous poor tolerance. The patient’s atypical symptoms, normal examination findings, and brain magnetic resonance imaging appearance assisted in excluding a diagnosis of demyelinating disease. The radiologic findings, termed white matter leukoaraiotic change, are commonly encountered in healthy persons as they age, particularly in patients with migraine or those with microvascular risk factors.
A Girl With Back Pain, Paresthesias, and Painful Vision Loss
Authors: Zivelonghi Cecilia , McKeon Andrew
Published: November 2021

A 12-year-old girl sought care for subacute onset of cramping back pain, along with paresthesias in her lower limbs up to the waistline, both hands, upper back, and chest, followed by rapidly progressive (over a few hours) painful vision loss affecting initially the right eye with subsequent involvement of the left eye. She underwent neuroophthalmologic evaluation and was diagnosed with bilateral optic neuritis. A positive Lhermitte sign was also present.

The patient was tested for aquaporin-4-immunoglobulin G autoantibodies, which were positive in both serum and cerebrospinal fluid.

A diagnosis of aquaporin-4-immunoglobulin G–positive neuromyelitis optica was made.

The patient was treated with rituximab (anti-CD20 monoclonal antibody) and became episode-free, with no further accumulation of disability.

The discovery of aquaporin-4-immunoglobulin G in 2004 has permitted the distinction of neuromyelitis optica spectrum disorder from other inflammatory central nervous system disorders. Aquaporin-4-immunoglobulin G represents a highly specific biomarker for neuromyelitis optica (almost 100% using molecular-based techniques), with sensitivity of approximately 80%. According to the most recent diagnostic criteria published in 2015, a diagnosis of neuromyelitis optica spectrum disorder can also be made for patients who are aquaporin-4-immunoglobulin G seronegative by any testing method, regardless of assay sensitivity, provided that more stringent clinical and radiologic requirements are met. Serial testing is recommended for these patients because late seroconversion has been described up to 4 years after the first episode.
Progressive Gait Difficulties
Authors: Collazo I. Vanessa Marin
Published: November 2021

A 58-year-old, right-handed man with a medical history of nephrolithiasis, essential hypertension, and type 2 diabetes sought care for a 6-year history of gait impairment. Initially, he noted subtle left foot and ankle weakness with associated falls that progressed over time. Two to 3 years later he again noted progressive left leg weakness and new arm weakness. Subsequently, progressive pain developed on the soles of his feet in addition to edema with erythematous discoloration around the left ankle and foot.

On neurologic examination, he was found to have mild upper motor neuron pattern weakness in the left arm and leg, most pronounced in the left hand finger extensor and left hip flexion and abduction. Left patellar reflex was brisk, and there was an extensor Babinski sign on the left. There was mild reduction in pinprick sensation in both feet. His gait was spastic with left leg circumduction.

Magnetic resonance imaging of the brain showed left-sided predominant periventricular and subcortical T2 fluid-attenuated inversion recovery hyperintensities. Magnetic resonance imaging of the cervical and thoracic spinal cord showed intramedullary cord T2 signal hyperintensities, eccentrically located on the left at C3, C5, C6, on the right at C7 to T1, and centrally at T4/T5 and T8/T9.

A diagnosis of primary progressive multiple sclerosis was made. The patient met the 2017 McDonald criteria for primary progressive multiple sclerosis.

After the diagnosis was confirmed and comprehensive education about the disease and the role of disease-modifying therapy was discussed with the patient, he was started on ocrelizumab. Gabapentin was started for management of painful foot paresthesias. Vitamin D3 supplementation was started. Physical therapy was also initiated.

Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system and is the leading cause of disability in the young population. Approximately 1 million people in the United States currently have multiple sclerosis.
Fatigue, Blurry Vision, and Swollen Optic Nerves
Authors: Acierno Marie D. , Bhatti M. Tariq , Chen John J. , Eggenberger Eric R.
Published: November 2021

A 71-year-old woman had development of generalized fatigue over 1 week, along with low-grade fever. The fever resolved, but the fatigue persisted. Subsequently, retro-orbital and head discomfort developed. One month later, she had blurred vision. An ophthalmic examination revealed mild dyschromatopsia, bilateral visual field constriction, bilateral marked optic disc edema, and vitreous cells graded as vitreous haze score 2.0.

Magnetic resonance imaging of the brain showed confluent abnormal areas of T2 hyperintensity without mass effect or enhancement involving the subcortical and periventricular white matter in the cerebral hemispheres bilaterally, basal ganglia, pons, and left thalamus. She had 2 lumbar punctures, which showed normal opening pressures. Cerebrospinal fluid analysis showed an increased white blood cell count cytologically consistent with reactive pleocytosis with a predominance of lymphocytes. The cerebrospinal fluid protein level was increased and cultures were negative for organisms. Immunostain confirmed polyclonal plasma cells and a possible T-cell proliferative disorder. The cerebrospinal fluid and serum were positive for collapsin-response mediator protein 5-immunoglobulin G and microtubule-associated protein 1B- immunoglobulin G antibodies at high titers. Computed tomography of the chest, abdomen, and pelvis showed an indeterminate pulmonary nodule in the upper lobe. Bronchoscopy identified thickened mucosa in the right lower lung consistent with small cell carcinoma. Positron emission tomography showed abnormal hypermetabolic areas of the ascending colon. Biopsy revealed tubulovillous adenoma of the ascending colon, and the patient underwent a right-sided colon resection and anastomosis.

The patient was diagnosed with paraneoplastic optic neuropathy (collapsin-response mediator protein 5-immunoglobulin G–associated optic neuropathy and vitritis).

Intravenous methylprednisolone was given for 5 days, followed by a prolonged course of oral prednisone, with slight visual improvement. The patient underwent a right-sided thoracotomy with biopsy of the right lower lobe, the results of which were consistent with small cell undifferentiated carcinoma.

Paraneoplastic neurologic syndromes are a heterogeneous group of disorders associated with various systemic cancers and with other mechanisms believed to be immune mediated. Paraneoplastic visual syndromes can precede or follow a diagnosis of cancer.
Progressive, Symmetrical, Painless Visual Loss
Authors: Eggenberger Eric R. , Acierno Marie D. , Bhatti M. Tariq , Chen John J.
Published: November 2021

A 75-year-old woman with a medical history of mixed connective tissue disease and breast adenocarcinoma sought care for subacute visual “haze” in both eyes characterized by light sensitivity, particularly with commercial fluorescent lighting, progressing over weeks. Visual acuity was 20/40 in each eye. The pupils were equal in size with no relative afferent pupillary defect but were sluggishly reactive to light. Automated perimetry documented peripheral constriction in both eyes. Ocular motility was normal. Ophthalmoscopy showed mild retinal pigment epithelial changes in both maculae with normal optic nerves.

Optical coherence tomography showed macular thinning in both eyes. Findings of fundus autofluorescence were normal. Serum testing documented the presence of 3 retinal antibodies, against 30-, 36-, and 46-kDa proteins. A paraneoplastic panel was negative except for low-level ganglionic (alpha 3) acetylcholine receptor autoantibody positivity, which was interpreted as nonspecific autoimmunity. Electroretinography indicated severely decreased scotopic and photopic a and b waves.

A diagnosis of paraneoplastic or nonparaneoplastic autoimmune retinopathy was made, consistent with the clinical presentation, optical coherence tomography and electroretinography findings, and the presence of retinal antibodies.

There are no established evidence-based guidelines to assist treatment decisions in autoimmune retinopathy, although several lines of therapy have been advocated.

No specific immunosuppressive therapy was undertaken in this case. However, if her vision had continued to rapidly worsen over time, empiric immunotherapy would have been instituted.

Autoimmune retinopathy includes paraneoplastic and nonparaneoplastic forms. The best-characterized autoimmune retinopathy phenotype is cancer-associated retinopathy. Cancer-associated retinopathy typically presents with subacute, painless, bilateral (although asymmetry has been described) vision loss that is progressive over weeks to months, reflecting both rod and cone dysfunction in most patients. Visual symptoms precede recognition of an underlying cancer in approximately 50% of cases.
Dancelike Movements in a Patient With a History of Rash
Authors: McKeon Andrew
Published: November 2021

A 67-year-old man visited the neurology clinic for new-onset, generalized, uncontrollable movements. His wife noticed onset of some unusual facial expressions and facial movements. This then evolved to him having some writhing movements of the left upper and left lower extremity. His speech and swallowing also became affected. He noted a tendency to bite his tongue, which was moving uncontrollably. Shortly before his neurology clinic visit, the same writhing movements of right-sided limbs developed. No cognitive or behavioral changes were reported.

He had been diagnosed with cutaneous lupus erythematosus 5 years previously after a malar rash of his face developed after sun exposure. The patient had a strong family history of autoimmunity, with 3 sisters having systemic lupus erythematosus. On physical examination, he had marked chorea, hyperkinetic movements that were unpredictable. When he walked in the hallway, he had a narrow-based gait, with some mild upper extremity hyperkinetic movements.

Because of the time course and the personal and family history of autoimmunity, autoimmune chorea was suspected. His cerebrospinal fluid demonstrated normal protein concentration, blood cell count, immunoglobulin G index and synthesis rate, and oligoclonal bands. Indirect immunofluorescence assays using HEp-2 substrate were positive for antinuclear antibody and Sjö‎gren syndrome-A antibody (anti-Ro).

Autoimmune chorea was diagnosed in the context of a known history of a limited form of systemic lupus erythematosus.

The patient received intravenous methylprednisolone infusions. Trimethoprim-sulfamethoxazole, double strength was given for Pneumocystis jirovecii prophylaxis. A rash developed, and the patient was determined to be sulfa allergic. Instead, he received atovaquone as prophylaxis. Three years later, the patient remained in remission from his chorea except for mild occasional hyperkinetic movements of his tongue.

In adults, autoimmune chorea is the most common form of chorea after levodopa-induced dyskinesias and Huntington disease. Patients have a subacute onset of symptoms and rapid progression. Patients may have accompanying neuropsychiatric symptoms.
Rapid-Onset Weakness and Numbness in a Patient With Systemic Lupus Erythematosus
Authors: Ernste Floranne C.
Published: November 2021

A 33-year-old woman with systemic lupus erythematosus, diagnosed 2 years prior and treated with hydroxychloroquine, sought care for a 4-week history of pain and paresthesias in her low back and lower extremities. She described a bandlike sensation of numbness starting in her midback which descended to both legs. Her symptoms progressed to constipation and inability to urinate adequately. She reported difficulty with ambulation. Over the course of 1 week of hospitalization, urinary and fecal incontinence developed.

On examination, she was alert and appropriately oriented. She had a malar rash and swelling of the metacarpophalangeal joints consistent with bilateral hand synovitis. Neurologic examination indicated hyperreflexia with brisk patellar and Achilles tendon reflexes bilaterally. She had trace motor weakness of the hip flexors, quadriceps, and hamstrings. She had loss of pinprick and temperature sensation in the lower extremities, extending beyond the saddle area to the T12 dermatome. Vibration perception and proprioception were preserved. She had a positive Babinski sign in the left foot. Her cerebellar examination showed slowing of rapid alternating movements in the left hand.

Magnetic resonance imaging of the lumbosacral spine indicated subtle T2 signal change of the intramedullary conus and enhancement of the cauda equina nerve roots. Cerebrospinal fluid analysis showed an increased protein concentration. Two white blood cells/µL were found in the cerebrospinal fluid. The serum antinuclear antibody was strongly positive, and the anti–double-stranded DNA antibody level was greater than 1,000 IU/mL. The serum complement levels were low. Lupus anticoagulant, beta-2 glycoprotein antibodies, and antiphospholipid antibodies were increased, at greater than twice the upper limits of normal. Electromyography indicated multiple sacral radiculopathies.

The patient was diagnosed with autoimmune myeloradiculitis as a neuropsychiatric manifestation of systemic lupus erythematosus (neuropsychiatric systemic lupus erythematosus).

The patient received methylprednisolone followed by prednisone, with a gradual taper. Her hospital course was complicated by the development of deep venous thromboses in the bilateral lower extremities. She was started on heparin and transitioned to warfarin therapy. She started mycophenolate mofetil. Hydroxychloroquine was continued. At a 24-month follow-up visit, the patient remained in neurologic remission.

Neuropsychiatric systemic lupus erythematosus events consist of a heterogeneous array of neurologic and psychiatric disorders including intractable headaches, cognitive dysfunction, psychosis, seizure disorders, transverse myelitis, aseptic meningitis, cranial neuropathies, and acute inflammatory demyelinating polyneuropathy.
Ascending Painful Paresthesias, Progressive Ataxia, and Bilateral Foot Drop
Authors: Campo Rocio Vazquez Do , Dubey Divyanshu
Published: November 2021

A 63-year-old woman had development of ascending paresthesias with lancinating and stabbing pain in all extremities. The symptoms began asymmetrically in the left leg and progressed to involve the right leg and both hands. She noticed progressive bilateral leg weakness, gait instability, and new numbness in the left middle back. She had recurrent falls and required the use of a cane and eventually a walker. She had 18.2 kg of weight loss. She had no autonomic symptoms or bladder or bowel dysfunction.

Examination 1 year after symptom onset showed an emaciated, ill-appearing woman. On neurologic examination, she had marked gait ataxia with profound proprioceptive loss in all extremities, asymmetrically reduced pinprick sensation distal to the left thigh, right knee, and both forearms, as well as bilateral middle thoracic dermatomes. She had bilateral foot drop and mild weakness in bilateral hamstring and intrinsic hand muscles. Her deep tendon reflexes were globally absent. Toes were mute to plantar stimulation.

Magnetic resonance imaging of the entire spine demonstrated subtle increased T2 signal in the posterior columns extending along cervical and thoracic segments and patchy gadolinium enhancement of the cervical and lumbosacral nerve roots. Electrodiagnostic testing demonstrated a length-dependent axonal sensorimotor peripheral neuropathy. Cerebrospinal fluid analysis showed an increased protein concentration, 9 cerebrospinal fluid-restricted oligoclonal bands, increased immunoglobulin G index and synthesis rate, and normal blood cell count. Paraneoplastic antibody evaluation showed high titers of collapsin-response mediator protein 5-immunoglobulin G autoantibodies in the serum and cerebrospinal fluid. Whole-body 18F-fludeoxyglucose–positron emission tomography indicated multiple hypermetabolic mediastinal and hilar lymph nodes. Biopsy of a mediastinal lymph node was consistent with small cell lung carcinoma.

The patient was diagnosed with collapsin-response mediator protein 5- immunoglobulin G paraneoplastic myeloneuropathy associated with small cell carcinoma of the lung.

The patient received a trial of intravenous methylprednisolone followed by chemotherapy, along with chest and prophylactic brain radiotherapy. She achieved a short period of clinical stabilization and mild improvement in gait and limb ataxia. Subsequently, her ataxia and bilateral leg weakness worsened. Her clinical condition rapidly deteriorated, and she became severely malnourished and bedridden, dying 12 weeks later, 2 years after symptom onset. Collapsin-response mediator protein 5- immunoglobulin G antibodies have been associated with asymmetric, painful polyradiculoneuropathy with coexisting myelopathy, often in the setting of thymoma or small cell lung cancer.
Difficult-to-Treat Polyradiculoneuropathy
Authors: Pinto Marcus V. R. , Dyck P. James B.
Published: November 2021

A 51-year-old healthy man sought care for a 6-month history of progressive, distal, lower extremity weakness, imbalance, and numbness in the feet. Neurologic examination showed a steppage gait, upper and lower extremity weakness, distal greater than proximal, absent tendon reflexes, and large fiber–predominant sensation loss in the feet. Nerve conduction studies showed marked temporal dispersion and slowed conductions. Cerebrospinal fluid analysis showed an increased protein concentration, 1 white blood cell/µL, and normal glucose level. Lumbar spine magnetic resonance imaging showed enlargement and enhancement of the nerve roots in the cauda equina, along with hypointensity in lumbar vertebral bodies. He underwent right sural nerve biopsy that showed an inflammatory demyelinating process. The patient was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and started on intravenous immunoglobulin. He was markedly worse at 12-week follow-up, with severe proximal and distal weakness and requiring the use of a walker. The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was revisited. Lumbar spine magnetic resonance imaging again showed enhancement of the nerve roots. Because of concern for neurolymphomatosis, a proximal fascicular nerve biopsy of the right sciatic nerve was performed. It showed the hallmark pathologic features of chronic inflammatory demyelinating polyradiculoneuropathy: endoneurial inflammation and signs of long-standing demyelination and remyelination with stacks on Schwann cell processes. The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was confirmed. Intravenous immunoglobulin was stopped, and the patient was started on an aggressive plasma exchange regimen. He had modest improvement. Azathioprine was also started. The patient continued to improve. He remained on this regimen for 2 years. Over the next year, the intravenous methylprednisolone dose was reduced. He was weaned off plasma exchange and intravenous methylprednisolone. At the last follow-up the disease was still in remission. Chronic inflammatory demyelinating polyradiculoneuropathy was described and named in 1975. It is a fairly symmetric peripheral neuropathy that usually presents with proximal and distal weakness, imbalance, and large fiber sensory dysfunction. Cerebrospinal fluid analysis shows albuminocytologic dissociation in 80% to 95% of those with typical chronic inflammatory demyelinating polyradiculoneuropathy.
Autoimmune Peripheral Nervous System Hyperexcitability
Authors: Klein Christopher J.
Published: November 2021

A 25-year-old man was seen for assessment of progressive pain. He had a distant history of Guillain-Barré syndrome at age 8 years, at which time he had symmetrical proximal and distal weakness of the upper and lower extremities with loss of ambulation. No facial weakness, dysarthria, dysphagia, ptosis, diplopia, or respiratory weakness occurred. At his initial evaluation there was touch hypersensitivity of the muscles and skin. He had no weakness or cognitive involvement, although the pain made it difficult for him to concentrate. His creatine kinase value improved with hydration, but pain and muscle twitching persisted. On examination, he had diffuse extremity and truncal fasciculations and myokymia and reported pain in not only the areas of twitching but also other areas of his extremities and trunk. On neurophysiologic testing, fibular and tibial motor compound muscle action potentials were decreased in amplitude, with normal ulnar and median motor responses. Needle electromyography of muscles proximally and distally showed diffuse spontaneous firing of muscles ranging in frequency with waxing and waning characteristics. These findings were thought to be consistent with a primary hyperexcitable disorder of muscles with a superimposed old polyradiculoneuropathy and possibly a myopathy. Expanded autoimmune neuroimmunologic testing of serum identified immunoglobulin G-directed cerebellar molecular staining consistent with voltage-gated potassium channel autoantibodies. Radioimmunoprecipitation assay identified voltage-gated potassium channel-immunoglobulin Gs and led to reflex testing for contactin-associated protein 2-immunoglobulin G; autoantibodies were positive. Computed tomography of the chest with contrast was performed, and lymphadenopathy was identified. The patient was clinically diagnosed with contactin-associated protein 2 - immunoglobulin G–positive Isaacs syndrome. A trial of high-dose gabapentin was attempted, with only mild benefits. Next, intravenous immunoglobulin was initiated. Diabetes developed, and he was hospitalized requiring initiation of insulin. His condition is now managed variably with intravenous immunoglobulin and scheduled daily gabapentin. The immune system has long been recognized to help regulate pain via non- immunoglobulin G–mediated mechanisms. Specifically, cytokines decrease the nociceptive nerve fiber thresholds and are released after diverse tissue insults. This allows for speeded healing by increased blood flow and protection of the region by pain guarding mechanisms. It is now recognized that, in rare cases, immunoglobulin G-mediated autoimmunity can lead to otherwise idiopathic pain disorders.
Bulbar-Predominant Weakness
Authors: Tracy Jennifer A. , Lennon Vanda A.
Published: November 2021

A 61-year-old man sought care for recurrent episodes of dysarthria for about 1 year. This symptom was more common after prolonged speaking. Six months before his evaluation he had significant slurring of his speech after talking for 3½ hours at work about a new project. This led to emergency evaluation and his symptoms were thought to represent a transient ischemic attack; he started aspirin and a statin. The episodes continued to recur. He also experienced intermittent binocular double vision, which did not improve with new eyeglasses, and a sensation that chewing and swallowing was more effortful. He noted that his arms and legs felt “heavy” at times. All these symptoms tended to occur later in the day or after exertion. Neurologic examination was remarkable for binocular double vision with prolonged gaze upward or to the far right. He could squat and rise 5 times but with difficulty by the 5th attempt. The patient’s symptoms suggested myasthenia gravis. The differential diagnosis for autoimmune myasthenia gravis, particularly with prominent ocular and facial muscle involvement, can include central nervous system disorders, motor neuron disease, and myopathy. Serologic evaluation showed positivity for acetylcholine receptor-binding antibody and acetylcholine receptor-modulating antibody. Striated muscle antibody was also positive. Thiopurine S-methyltransferase activity was low. Repetitive stimulation studies showed a decrement in the right facial nerve, which partially improved after exercise. Routine needle examination showed motor unit variation in the right orbicularis oculi. Single-fiber electromyography showed increased jitter in the right orbicularis oculi. Chest computed tomography showed scattered tiny pulmonary nodules but no evidence of thymoma or other neoplasm. The clinical diagnosis was autoimmune generalized myasthenia gravis, seropositive for acetylcholine receptor antibody, without evident thymoma or other neoplasm. The patient was initially treated with oral pyridostigmine with some symptomatic benefit. Oral prednisone was then initiated; symptoms resolved when the dose was titrated. Calcium and vitamin D supplements, as well as Pneumocystis prophylactic therapy, were initiated concurrently. Mycophenolate mofetil was added as a steroid-sparing agent. On thoracic surgery consultation, thymectomy was recommended. Autoimmune myasthenia gravis is a disorder of impaired neuromuscular transmission caused by immunoglobulin G-mediated attack on a critical component of the acetylcholine receptor signaling complex in the muscle’s postsynaptic membrane. The most commonly identified antibodies, target the nicotinic acetylcholine receptor.