Patient-Reported Impact of Symptoms in Fibromyalgia (PRISM-FM).

J Rheumatol 2024; doi: 10.3899/jrheum.2023-0698 Lynne Kennedy Matallana, MS, was missing from the author byline and footnotes. Her affiliation is National Fibromyalgia Association, Newport Beach, California, USA. She declares no conflicts of interest relevant to the article. This correction applies only to the February 15 2024 First Release. The correct author byline and footnotes appear in the print and online issues.

Friedreich Ataxia Caregiver-Reported Health Index: Development of a Novel, Disease-Specific Caregiver-Reported Outcome Measure.

Background and Objectives: The Friedreich ataxia (FRDA) scientific community needs access to patient-centered outcome measures that satisfy regulatory guidelines and are capable of tracking clinically meaningful changes in FRDA disease burden. The objective of this research was to develop a novel, disease-specific caregiver-reported outcome measure for use in FRDA research and clinical care. Methods: In prior work, we conducted qualitative interviews and a cross-sectional study of FRDA caregivers and patients to determine the symptoms of greatest importance to individuals with FRDA. We designed the Friedreich Ataxia Caregiver-Reported Health Index (FACR-HI) to serially measure the symptoms of greatest importance to patients and utilized factor analysis, beta testing, reliability testing, and cross-sectional subgroup analysis to further evaluate and optimize this disease-specific outcome measure. Results: The FACR-HI was designed to measure total disease burden and disease burden in 18 symptomatic domains. The FACR-HI total score demonstrated high internal consistency (Cronbach's α = 0.98) and test-retest reliability (intraclass correlation coefficient = 0.96). Beta interview participants found the FACR-HI to be highly relevant, comprehensive, and easy to use. FACR-HI total and subscale scores were associated with functional staging for ataxia scores and speech impairment. Discussion: Initial evaluation of the FACR-HI supports its content validity, test-retest reliability, and construct validity as a caregiver-reported outcome measure for assessing how pediatric individuals with FRDA feel and function. The FACR-HI provides a potential mechanism to quantify changes in multifactorial FRDA disease burden during future clinical trials.

Patient-reported impact of symptoms in adrenoleukodystrophy (PRISM-ALD).

BACKGROUND: Adrenoleukodystrophy (ALD) is a multifaceted, X-linked, neurodegenerative disorder that comprises several clinical phenotypes. ALD affects patients through a variety of physical, emotional, social, and other disease-specific factors that collectively contribute to disease burden. To facilitate clinical care and research, it is important to identify which symptoms are most common and relevant to individuals with any subtype of ALD. METHODS: We conducted semi-structured qualitative interviews and an international cross-sectional study to determine the most prevalent and important symptoms of ALD. Our study included adult participants with a diagnosis of ALD who were recruited from national and international patient registries. Responses were categorized by age, sex, disease phenotype, functional status, and other demographic and clinical features. RESULTS: Seventeen individuals with ALD participated in qualitative interviews, providing 1709 direct quotes regarding their symptomatic burden. One hundred and nine individuals participated in the cross-sectional survey study, which inquired about 182 unique symptoms representing 24 distinct symptomatic themes. The symptomatic themes with the highest prevalence in the overall ALD sample cohort were problems with balance (90.9%), limitations with mobility or walking (87.3%), fatigue (86.4%), and leg weakness (86.4%). The symptomatic themes with the highest impact scores (on a 0-4 scale with 4 being the most severe) were trouble getting around (2.35), leg weakness (2.25), and problems with balance (2.21). A higher prevalence of symptomatic themes was associated with functional disability, employment disruption, and speech impairment. CONCLUSIONS: There are many patient-relevant symptoms and themes that contribute to disease burden in individuals with ALD. These symptoms, identified by those having ALD, present key targets for further research and therapeutic development.

Patient-Reported Impact of Symptoms in Fibromyalgia (PRISM-FM).

OBJECTIVE: To identify the frequency and relative importance of symptoms experienced by adults with fibromyalgia (FM) and determine factors associated with a higher disease burden. METHODS: We conducted semistructured interviews with 15 participants with FM, collecting 1479 quotes regarding the symptomatic burden of FM. We then performed an international cross-sectional study involving 1085 participants with FM to determine the prevalence and relative importance (scale 0-4) of 149 symptoms representing 14 symptomatic themes. We performed subgroup analysis to determine how age, sex, disease duration, medication use, employment status, change in employment status, missing work due to FM, and ability level are related to symptomatic theme prevalence. RESULTS: The symptomatic themes with the highest prevalence in FM were pain (99.8%), muscle tenderness (99.8%), and fatigue (99.3%). The symptomatic themes that had the greatest effect on patients' lives were related to fatigue (2.88), pain (2.85), muscle tenderness (2.79), and impaired sleep and daytime sleepiness (2.70). Symptomatic theme prevalence was most strongly associated with the modified Rankin Scale level of disability, disability status, and change in employment status (on disability vs not on disability). CONCLUSION: Participants with FM identify a variety of symptoms that significantly affect their daily lives. Many of these symptoms, such as fatigue, sleep disturbance, and activity limitation, are life-altering and not related to traditional diagnostic criteria. Symptom prevalence in this population varies across subgroups based on demographic categories and disability status.

Benign paroxysmal positional vertigo in a patient with persistent hypoglossal artery and bilateral madelung deformity.

We explore a case of Benign Paroxysmal Positional Vertigo in the context of Persistent Hypoglossal Artery (PHA) and bilateral Madelung Deformity (MD). PHA is associated with a raft of major adverse cardiovascular events. MD can result from manifold conditions such as Turner's Syndrome and mesomelic dwarfism. In this case, the patient's positive family history of MD across generations is suggestive of inherited mutation in the Short Stature Homeobox (SHOX) Gene. We discuss the putative impact of SHOX on the genesis of Benign Paroxysmal Positional Vertigo (BPPV) in a patient with PHA and bilateral MD.

Historical Perspective and Medical Maladies of Alexander the Great.

Alexander the Great (356 BC - 323 BC) was only 20 years old when he was named the next King of Macedonia after his father was assassinated. The following 11 years witnessed the evolution of an outstanding leader who expanded his empire from Egypt to the Indian frontier. Despite successfully conquering much of the world, he was afflicted with a febrile illness at the age of 32, which he battled for a mere 11 days before perishing. It has been almost 2,400 years since his death, but the exact cause remains a mystery. Did he die of natural causes or at the hands of conspirators? Numerous papers have been written about the illnesses suffered by Alexander, with the current evidence revealing a healthy 32-year-old man who developed fever and acute abdominal pain with rapid deterioration of his general condition leading to death within a short duration. We analyze various theories and discuss possible etiologies that may have contributed to his tragic death. Information was gathered from primary and secondary sources found through searching multiple online academic databases and the University of Southern California (USC), University of California Los Angeles (UCLA), and Harvard libraries. Unreliable sources and the unavailability of Alexander's body for autopsy make reaching a definitive diagnosis an impossible task; however, based on existing information, we presume that he most probably died of a neurological cause due to acute necrotizing pancreatitis and encephalopathy secondary to peritonitis. Other potential causes include fulminant hepatic failure, acute demyelinating neuropathy or Guillain Barre Syndrome, and arsenic poisoning.

Novel NUDT2 variant causes intellectual disability and polyneuropathy.

Exome or genome sequencing was performed to identify the genetic etiology for the clinical presentation of global developmental delay, intellectual disability, and sensorimotor neuropathy with associated distal weakness in two unrelated families. A homozygous frameshift variant c.186delA (p.A63Qfs*3) in the NUDT2 gene was identified in cases 1 and 2 from one family and a third case from another family. Variants in NUDT2 were previously shown to cause intellectual disability, but here we expand the phenotype by demonstrating its association with distal upper and lower extremity weakness due to a sensorimotor polyneuropathy with demyelinating and/or axonal features.

A Rare Case of Charcot-Marie-Tooth Disease Type 1C With an Unusual Presentation.

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an inherited demyelinating neuropathy characterized by distal muscle weakness and atrophy. Charcot-Marie-Tooth disease type 1C (CMT1C) is a rare form of CMT1 caused by mutations in the lipopolysaccharide-induced tumor necrosis factor (LITAF) or small integral membrane protein of the lysosome/late endosome (SIMPLE) gene. Phenotypically, CMT1C is characterized by sensory loss and slow conduction velocity, and is typically slowly progressive and often associated with pes cavus foot deformity and bilateral foot drop. A 42-year-old female presented with a 10-year history of slowly progressive bilateral calf pain and cramps. After multiple electromyography/nerve conduction studies (EMG/NCS) and genetic testing, the patient was revealed to have CMT1C with a heterozygous pathogenic variant, c.334G>A (p.Gly112Ser). However, the presentation of the patient's CMT1C phenotype was unusual compared to patients with similar diagnosis in a previous study, including a normal sensory exam with the exception of high arches and mildly reduced vibratory sense. Additionally, the patient's teenage son already started showing symptoms of CMT1C despite the fact that the onset of the disease typically occurs at an older age. This particular case further highlights the idea that the phenotype related to CMT1C may have a wide spectrum of disease severity.

Historical perspective of neurology in Iran.

Iran is an ancient country, known as the cradle of civilization. The history of medicine in Iran goes back to the existence of a human in this country, divided into three periods: pre-Islamic, medieval, and modern period. There are records of different neurologic terms from the early period, while Zoroastrian (religious) prescription was mainly used until the foundation of the first medical center (Gondishapur). In the medieval period, with the conquest of Islam, prominent scientists were taught in Baghdad, like Avicenna, who referred to different neurologic diseases including stroke, paralysis, tremor, and meningitis. Several outstanding scientists developed the medical science of neurology in Iran, the work of whom has been used by other countries in the past and present. In the modern era, the Iranian Neurological Association was established with the efforts of Professor Jalal Barimani in 1991.

A case of Fragile X-associated tremor/ataxia syndrome (FXTAS).

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder associated with dysfunction of movement, memory, and the peripheral nervous system. We report an 82 years old male who presented with tremors and difficulty with balance that started at 65 years of age. His motor examination revealed decreased strength in left lower extremity. Tremors were seen in both the upper limbs at rest that worsened with movement. Bilateral lower extremities showed absent vibration and proprioception sensations, absent reflexes and upgoing toes. Electrodiagnostic studies revealed sensory predominant axonal sensory-motor peripheral polyneuropathy. Brain MRI revealed microvascular ischemic changes. The cervical and lumbar MRI showed diffuse degenerative changes. Genetic test for heritable causes of ataxia revealed a premutation in Fragile X gene (84 CGG repeats), confirming the diagnosis of FXTAS. On further genetic testing three out of his four daughters also tested positive for the FMR1 premutation. In appropriate clinical setting, Fragile X-associated tremor/ataxia syndrome (FXTAS) should be considered in every middle aged/elderly patient who presented with slowly progressive ataxia, tremor and peripheral polyneuropathy without any history of cognitive or neurological disabilities in childhood.

An Overview of Neuromuscular Junction Aging Findings in Human and Animal Studies.

BACKGROUND: Aging is a complex irreversible process that is not only related to an individual's genetic make-up but also to lifestyle choices and environmental exposures. Like every other structure in human body, the Neuromuscular Junction (NMJ) is not averse to aging. OBJECTIVES: The prime objective is to analyse the microscopic and macroscopic changes at the NMJs with aging. METHODS: For the purpose of review we evaluated data from resources like Pubmed, Ovid, UCLA libraries and USC libraries. RESULTS: We review various morphological, physiological, immunological, and biochemical changes in NMJs with aging and their management. CONCLUSION: The alterations in NMJs secondary to aging are inevitable. It is vital that neurologists clearly understand the pathophysiology of NMJ aging and differentiate between physiological and pathological effects of aging. With the current knowledge of science, the changes in NMJ aging can be better prevented rather than cured.

Non-GNE Quadriceps Sparing Distal Myopathy in an Iranian Jewish Patient.

GNE myopathy is an autosomal-recessive distal myopathy. It is caused by a hypomorphic GNE gene, encoding the rate-limiting enzyme in sialic acid synthesis. This myopathy is prevalent in the Iranian Jewish (IJ) descendants because of a founder mutation GNE: p. M712T. We report a 52-year-old IJ woman who presented with a 20-year history of progressive distal muscle weakness. Physical examination and magnetic resonance imaging revealed lower-extremity weakness and atrophy. Electromyography confirmed myopathy. Genetic testing showed no mutations on the GNE gene. Muscle histochemistry demonstrated no rimmed vacuoles. The analysis of polysialylated neural cell adhesion molecule Western blot pattern was negative. Non-GNE myopathy with quadriceps sparing presentation has been previously described in a few cases of non-IJ descents. To the best of our knowledge, this is the first case of an IJ patient, presenting with quadriceps sparing myopathy, without associated GNE mutations and/or tubule-filamentous inclusions.

A Case of Sjögren's Syndrome Mimicking Inflammatory Myopathy.

Sjögren's syndrome (SS) is a chronic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands and causing the decreased function of lacrimal and salivary glands. We describe a case of a 34-year-old male who presented with Sjögren's syndrome presenting as myopathy and sensorimotor neuropathy. His creatinine kinase levels were elevated with positive anti-Sjögren's syndrome-related antigen A autoantibodies and anti-Sjögren's syndrome Type B autoantibodies. Electromyography showed evidence of irritable myopathy. Parotid gland biopsy demonstrated focal lymphocytic sialadenitis. The patient favorably responded to high-dose steroids. Thus, although rare, inflammatory myopathy must be considered part of the initial presentation of Sjögren's syndrome.

Hydroxychloroquine-induced autophagic vacuolar myopathy with mitochondrial abnormalities.

Hydroxychloroquine (HCQ) and chloroquine are used worldwide for malaria as well as connective and rheumatological disorders. They have been reported to be linked to myopathy in patients. We report four patients who were receiving HCQ as part of treatment for connective tissue disorder and who presented with myopathy. The muscle biopsy in these patients was consistent with findings of HCQ toxicity. HCQ muscle toxicity is usually self-limiting after discontinuation of the drug. It also usually tends to be under-reported due to presence of various confounding factors. This warrants close monitoring and consideration of muscle biopsy as part of initial work up of patients who present with myopathy while receiving HCQ.

"Dystrophia Myotonica" and the Legacy of Hans Gustav Wilhelm Steinert.

The objective of this analysis is to study the life of Hans Gustav Wilhelm Steinert and his role in identifying several neurologic disorders including myotonic dystrophy (DM). DM type 1 (DM1) is a commonly inherited adult muscle disorder. In 1909, its characteristics were first described by Hans Steinert (1875-1911), a German neurologist. Born in Dresden, Germany, Steinert studied philosophy and medicine at the Universities of Leipzig, Berlin, Freiberg, and Kiel. There, under the supervision of Heinrich Curschmann, he accomplished his own works on aphthongia, cerebral muscular atrophy, and cerebral hemiplegia. In 1909, he published his study on six patients exhibiting characteristic myotonia. With autopsy findings of muscular fibrosis, Steinert identified this independent symptom complex as "Dystrophien Myotoniker" (DM). Overall, Steinert's accurate clinical characterization, coupled with the first ever autopsy finding of this condition, laid the foundations of our current understanding about DM1. This review serves as a tribute to the achievements of Hans Steinert and provides an opportunity to understand the historical perspective of DM1. Information for this analysis was gathered from PubMed and libraries at University of Southern California and University of California, Los Angeles. In addition, personal communications with Professor Benedikt Schoser at The University of Munich, Professor Tiemo Grimm at The University of Wuerzburg, and Professor Peter Harper at The University of Wales are acknowledged.

Ischemic Stroke in a Patient with Parry-Romberg Syndrome.

OBJECTIVE: This study aimed to discuss a case of a patient with a known diagnosis of Parry-Romberg syndrome (PRS) presenting with ischemic stroke, the second such reported case. BACKGROUND: PRS is a rare genetic disorder with progressive hemifacial atrophy, which usually presents within the first 2 decades of life. Neurologic manifestations include trigeminal neuralgia with associated deafness, hemifacial pain with associated migraine headaches, seizures, movement disorders, and neuropsychiatric symptoms. Many patients have elevated antinuclear antibody (ANA) titers. However, stroke is uncommon. CASE DESCRIPTION: A 34-year-old right-handed woman, diagnosed with PRS at age 15, presented with right-sided weakness on waking up. Brain magnetic resonance imaging revealed a small infarct of the posterior limb of the left internal capsule. Vessel imaging revealed an aberrant right subclavian artery. Atrophy of the right-sided muscles of mastication is consistent with her known diagnosis of right-sided PRS. Stroke workup revealed a patent foramen ovale; however, no evidence of deep venous thrombosis was found. Hypercoagulability workup revealed an elevated ANA. The cause of stroke in this patient with PRS remains unclear, as she has no known risk factors. CONCLUSION: It is possible that elevated inflammatory markers associated with PRS may cause a proinflammatory state and predispose patients to small-vessel vasculopathy. It is important to note the association between PRS and ischemic stroke.