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.

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.

Cardiac Abnormalities in Congenital and Childhood Myotonic Muscular Dystrophy Type 1.

Myotonic dystrophy often presents with cardiac abnormalities, particularly conduction defects, that factor into an increased risk of sudden cardiac death. Myotonic dystrophy has two forms, myotonic dystrophy type 1 (DM1) and DM2, and is a multisystemic disorder that presents in a wide, clinical spectrum and age range. A distinguishing feature of DM1 is the existence of a congenital form. Though research on cardiac involvement has been conducted on patients with the adult form of myotonic dystrophy, there have been few studies focused on cardiac involvement in pediatric patients with congenital myotonic dystrophy type 1 (CDM1). In this study, a survey was conducted to determine the prevalence and variations of cardiac abnormalities in pediatric patients with CDM1. This preliminary study found a prevalence of 25.8% CDM1 pediatric patients with cardiac abnormalities in a sample size of 31 patients.

Spirituality and Religiosity and Its Role in Health and Diseases.

Religiosity is a factor involved in the management of health and diseases/patient longevity. This review article uses comprehensive, evidence-based studies to evaluate the nature of religiosity that can be used in clinical studies, thus avoiding contradictory reports which arise from misinterpretation of religiosity. We conclude that religiosity is multidimensional in nature and ultimately associated with inherent protection against diseases and overall better quality of life. However, a number of untouched aspects of religiosity need to be investigated further before we can introduce religiosity in its fully functional form to the realm of health care.

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.

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.

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.

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 Tuberculosis-related Leukocytoclastic Vasculitis Presenting With Peripheral Neuropathy.

Tuberculous granulomatous vasculitis is commonly associated with meningitis and retinitis. We describe a 39-year-old male, with a history of pulmonary tuberculosis (TB) who presented with progressive weakness, pain, tingling and numbness in the bilateral lower extremities. Significant atrophy and weakness of the lower extremities were evident along with absent reflexes. Nerve conduction studies and electromyography showed severe axonal polyneuropathy and denervation on the lower extremities. Nerve biopsy demonstrated small vessel leukocytoclastic vasculitis without any granuloma formation. Muscle biopsy was consistent with denervation and atrophy with target fiber changes. Tuberculosis-related vasculitis causing peripheral neuropathy is extremely rare and our case is unique in manifesting this presentation.

Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing Pitfalls of Exome Sequencing.

Here, we present a case of a 31-year-old man with progressive cognitive decline, ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic studies over the course of several years failed to yield a diagnosis. Initial whole exome sequencing through a commercial laboratory identified several variants of uncertain significance; however, follow-up clinical examination and testing ruled each of these out. Eventually, repeat whole exome sequencing identified a known pathogenic intronic variant in the NPC1 gene (NM_000271.4, c.1554-1009G>A) and an additional heterozygous exonic variant of uncertain significance in the NPC1 gene (NM_000271.4, c.2524T>C). Follow-up biochemical testing was consistent with a diagnosis of probable Niemann-Pick disease Type C (NP-C). This case illustrates the potential of whole exome sequencing for diagnosing rare complex neurologic diseases. It also identifies several potential common pitfalls that must be navigated by clinicians when interpreting commercial whole exome sequencing results.

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.

Changes in functional magnetic resonance imaging with Yogic meditation: A pilot study.

BACKGROUND: The neural substrates of Yogic meditation are not well understood. Meditation is theorized to be a conscious mental process that induces a set of complex physiological changes within the areas of the brain termed as the "relaxation response." AIMS AND OBJECTIVE: Pilot data of a functional magnetic resonance imaging (fMRI) study is presented to observe and understand the selective activations of designated brain regions during meditation. MATERIAL AND METHODS: Four trained healthy Patanjali Yoga practitioners in their mid-60s participated in this prototype interventional study. A three-part 1-min block design alternating between meditation (test) and relaxation (control) phase with an imaginary visual fixation and auditory stimulation was used. RESULT AND OBSERVATION: The fMRI images revealed strong activation in the right prefrontal regions during the visual and auditory fixation meditation phases compared to no activations during the relaxation phase. A comparison between the visual and auditory fixations revealed shifts within the prefrontal and temporal regions. In addition, activation in occipital and temporal regions was observed during the meditation phase. Occipital lobe activation was more apparent during visual meditation phase. CONCLUSION: It is concluded that specific fMRI brain activations are observed during different forms of Yogic meditation (visual and auditory phases). Occipital and prefrontal activation could be modulating the known neurophysiological and biological effects of meditation.

The therapeutic value of yoga in neurological disorders.

BACKGROUND: The ancient mind and body healing methods of yoga recently sparked fervor in the scientific community as an alternative and complementary means of therapy. Since the World Health Organization officially began promoting yoga in developing countries in 1978, yoga has been cited for its therapeutic potential and has been widely recognized in Western culture. However, as an increasing number of people practice yoga for remedial purposes, researchers raise two important questions: 1) Is yoga a valid complementary management and rehabilitation treatment modality? 2) What conditions show promise of treatment with this intervention?. OBJECTIVE: This review article uses comprehensive scientific, evidence-based studies to analyze the efficacy of various basic and applied aspects of yoga in disease prevention and health promotion. It specifically intends to expose the effects of yoga in neurological disorders, particularly epilepsy, stroke, multiple sclerosis, Alzheimer's disease, peripheral nervous system disease, and fibromyalgia. MATERIALS AND METHODS: Information was gathered from various resources including PubMed, Ovid, MD-Consult, USC, and U.C.L.A. libraries. Studies were selected and reviewed on the basis of sample size, control, randomization, double-blinding, and statistical analysis of results. RESULTS: The pratice of yoga and meditation demonstrates statistically encouraging physiological and psychological improvements in the aforementioned neurological disorders. However, there were certain flaws and inadequacies in the study designs employed to evaluate the same. A critical analysis of these studies is presented. CONCLUSIONS: With the aim to focus attention on this widespread yet largely unexamined treatment modality, this paper seeks to provide direction and support for further research necessary to validate yoga as an integrative, alternative, and complementary therapy.