Spinal Muscular Atrophy in the Treatment Era
Spinal muscular atrophy is an autosomal-recessive degenerative neuromuscular disease that has historically been categorized into 5 types based on the individual ’s best functional ability. Two rather remarkable treatments have recently been approved for commercial use, and both have markedly changed the natural history of this disease. Here the authors report several cases of individuals, ranging from infants to adults, to highlight diagnostic considerati ons, along with initial and long-term treatment considerations in these individuals who now have the potential for stabilization to significant improvement in funct...
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Megan A. Waldrop, Bakri H. Elsheikh Source Type: research
Case Studies on the Genetic and Clinical Diagnosis of Facioscapulohumeral Muscular Dystrophy
We present 6 cases to illustrate both clinical and genetic diagnostic challenges in facioscapulohumeral muscular dystrophy and provide examples on how to navigate the different steps of genetic testing. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Johanna Hamel, Rabi Tawil Source Type: research
Congenital Myasthenic Syndromes
Congenital myasthenic syndromes comprise a rare heterogeneous group of diseases that impair neuromuscular transmission and are characterized by muscle fatigability and transient or permanent weakness. Symptoms are often present from birth or early childhood. These syndromes have a wide range of phenotypes and severity. Caused by genetic mutations in any of the numerous genes encoding for components of the neuromuscular junction. They are classified by where in the neuromuscular junction the mutated component is located: presynaptic, synaptic, or postsynaptic. Mutations in about 30 genes have been implicated. Diagnosis can ...
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Stanley Jones P. Iyadurai Source Type: research
Limb Girdle Muscular Dystrophies
The limb girdle muscular dystrophies (LGMDs) are genetic muscle diseases with primary skeletal muscle involvement in persons with the ability to walk independently at some point in the disease course. They usually have increased creatine kinase levels along with patterns of fatty and fibrous deposition on muscle imaging and/or dystrophic features on muscle biopsy. Distinctive clinical features provide valuable diagnostic clues to the diagnosis and sometimes treatment of these disorders. The advent of gene and cell-based therapies; gene replacement, editing, and modulation; along with stem cell and small molecule therapies ...
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Jacob Bockhorst, Matthew Wicklund Source Type: research
Diabetic Lumbosacral Radiculoplexus Neuropathy (Diabetic Amyotrophy)
This article provides a series of interesting cases to highlight the diagnostic challenges and discusses management decision making. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Melanie D. Glenn, Duaa Jabari Source Type: research
Differential Diagnoses of Inclusion Body Myositis
This article discusses atypical cases and differential diagnoses and considers the role of imaging and histopathology in differentiating inclusion body myositis. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Vinojini Vivekanandam, Enrico Bugiardini, Ashirwad Merve, Matthew Parton, Jasper M. Morrow, Michael G. Hanna, Pedro M. Machado Source Type: research
Small Fiber Neuropathy
Small fiber neuropathy has a broad array of presentations. Length-dependent symptoms and findings present little diagnostic difficulty, but non –length-dependent or multifocal symptoms can be challenging. Intraepidermal nerve fiber density (IENFD) testing in apparent fibromyalgia warrants further study, but skin biopsy testing of this patient population is reasonable. Avoidance of IENFD testing in situations where diagnosis of neuropathy is already clear or where neuropathy is not the cause of symptoms helps to prevent incorrect conclusions. Careful history and physical examination plus pretest probability are i...
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: David S. Saperstein Source Type: research
This article uses a case-based format to review the clinical reasoning and diagnostic tools that guide the accurate diagnosis of myopathies. We specifically focus on toxic, metabolic, mitochondrial, and late-onset congenital myopathies. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Yessar Hussain, Samantha Miller Source Type: research
Skeletal Muscle Channelopathies
Skeletal muscle channelopathies are rare genetic neuromuscular conditions that include the nondystrophic myotonias and periodic paralyses. They cause disabling muscle symptoms and can limit educational potential, work opportunities, socialization, and quality of life. Effective therapy is available, making it essential to recognize and treat this group of disorders. Here, the authors highlight important aspects regarding diagnosis and management using illustrative case reports. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Vinojini Vivekanandam, Pinki Munot, Michael G. Hanna, Emma Matthews Source Type: research
This article discusses cases, diagnostic tools, associated antibodies, and pathology. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Suur Biliciler, Justin Kwan Source Type: research
Neuromuscular disorders (NMD) is probably the most dynamic neurology subspecialty. The incidence of NMD as a group (160/100,000) is comparable to that of Parkinson disease and is increasing due to improved diagnosis and management. NMD carry high mortality and morbidity and economic burden. (Source: Neurologic Clinics)
Source: Neurologic Clinics - July 21, 2020 Category: Neurology Authors: Aziz Shaibani Source Type: research
Therapeutic and Diagnostic Challenges in Myasthenia Gravis
This article highlights several cases that the practicing neurologist may encounter in the treatment of MG. Diagnostic uncertainty continues to be an issue in patients who are seronegative to the 2 most common antibodies , acetylcholine receptor and muscle-specific tyrosine kinase (MuSK). Specific populations of patients with MG including MuSK MG, thymomatous MG, refractory MG, and pregnant women also require special consideration. This article reviews specific cases and an update on current management.” (Source: Neurologic Clinics)
Source: Neurologic Clinics - June 11, 2020 Category: Neurology Authors: Thy Nguyen, Cecile L. Phan, Emilio Supsupin, Kazim Sheikh Source Type: research
Refractory Chronic Immune-mediated Demyelinating Polyneuropathy
This article discusses videos of cases referred to a tertiary medical center for “refractory CIDP” and pitfalls in the diagnosis and management of this condition. (Source: Neurologic Clinics)
Source: Neurologic Clinics - June 11, 2020 Category: Neurology Authors: Aziz Shaibani, Husam Al Sultani Source Type: research
The distal myopathies are a rare and heterogeneous group of neuromuscular disorders. Patients present with weakness of the hands, distal lower extremities, or both. Age of onset varies from early childhood to late adulthood. Most of the disorders causing distal myopathic weakness are genetically based. The list of genetic disorders associated with distal-onset weakness is ever-expanding and complicated by pronounced genetic heterogeneity, phenotypic variability, and complex multisystem involvement. There are no known effective disease-modifying treatments for the distal myopathies. Evaluation, symptomatic management, and p...
Source: Neurologic Clinics - June 11, 2020 Category: Neurology Authors: Kevin J. Felice Source Type: research
This article spans the common, well-defined inflammatory demyelinating polyradiculoneuropathies (Guillain-Barr é syndrome and chronic inflammatory demyelinating polyradiculoneuropathy) to the rarer, acquired demyelinating neuropathy variants (Miller-Fisher syndrome and multifocal motor neuropathy), vasculitic neuropathies, and sensory neuronopathies (dorsal root ganglionopathies). These case studies illustr ate the characteristic clinical patterns of the immune-mediated neuropathies encountered in neurologic practice. Recommendations for diagnostic evaluation and treatment approach accompany each case. Prompt recogn...
Source: Neurologic Clinics - June 11, 2020 Category: Neurology Authors: Kelly G. Gwathmey, A. Gordon Smith Source Type: research
Advances in the Genetic Testing of Neuromuscular Diseases
This article presents cases to illustrate testing algorithms that may establish cases of mosaicism of the proband or parent, mitochondrial DNA mosaicism, genomic rearrangements, or novel genetic diagnoses. (Source: Neurologic Clinics)
Source: Neurologic Clinics - June 11, 2020 Category: Neurology Authors: Perry B. Shieh Source Type: research
Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure; however, symptomatic management has an impact on quality of life and survival. Symptom management is best performed in a multidisciplinary care setting, where patients are evaluated by multiple health care professionals. Respiratory failure is a significant cause of morbidity and mortality in patients with ALS. Early initiation of noninvasive ventilation can prolong survival, and adequate use of airway clearance techniques can prevent respiratory infections. Preventing and treating weight loss caused by dysphagia may slow down disease progression, and exp...
Source: Neurologic Clinics - June 11, 2020 Category: Neurology Authors: Jonathan R. Brent, Colin K. Franz, John M. Coleman, Senda Ajroud-Driss Source Type: research
Case Studies in Management of Muscle Cramps
Muscle cramps, defined as a painful contraction of a muscle or muscle group, are a common symptom most people have experienced throughout their lifespan. In some cases cramps can be frequent, severe, and disabling, thus requiring medical assessment and intervention. Physiologic states such as pregnancy and exercise are associated with excessive muscle cramps, as are numerous medical and neurologic conditions, medications such as diuretics and statins, and peripheral nerve hyperexcitability syndromes. Treatment options for muscle cramps are limited, although recent studies have shown that mexiletine could be a safe and effi...
Source: Neurologic Clinics - June 10, 2020 Category: Neurology Authors: Hans D. Katzberg Source Type: research
Treatment of Paroxysmal Dyskinesia
Paroxysmal dyskinesia (PxD) is a heterogeneous group of syndromes characterized by recurrent attacks of abnormal movements, triggered by detectable factors, without loss of consciousness. According to the precipitating factors, they are classified as paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dystonia (PED). PxD treatment is based on the combination of nonpharmacologic and pharmacologic approaches. Pharmacologic and nonpharmacologic treatments effective for PNKD and PED also are available. In PxD refractory to conventional treatment, surgery might ...
Source: Neurologic Clinics - April 10, 2020 Category: Neurology Authors: Anna Latorre, Kailash P. Bhatia Source Type: research
Principles of Medical and Surgical Treatment of Cerebral Palsy
Cerebral palsy is the most common cause of childhood motor disability, affecting 2 to 3/1000 children worldwide. Clinical abnormalities in tone, posture, and movement are the result of brain dysgenesis or injury early in life, and impairment varies in type, distribution, and in severity. The underlying brain disorder may also lead to other associated neurologic and systemic impairments. Variability in functional impairments, which can change during development, necessitates an individualized treatment plan. Treatment options are primarily symptomatic and directed toward optimizing independence, function, and/or ease of car...
Source: Neurologic Clinics - April 10, 2020 Category: Neurology Authors: Eric M. Chin, Hilary E. Gwynn, Shenandoah Robinson, Alexander H. Hoon Source Type: research
Treatment of Movement Disorders
Movement disorders are a group of neurologic conditions characterized phenomenologically by slowness and paucity of movement (hypokinetic disorders) or abnormal excessive involuntary movements (hyperkinesias). The hypokinetic movement disorders are exemplified by Parkinson disease and other parkinsonian disorders. Hyperkinetic movement disorders include tremors, dystonia, tics, chorea, athetosis, ballism, stereotypy, and akathisia. Ataxia, gait disorders, and spasticity are also often included among movement disorders. (Source: Neurologic Clinics)
Source: Neurologic Clinics - April 10, 2020 Category: Neurology Authors: Joseph Jankovic Tags: Preface Source Type: research
Medical and Surgical Treatments of Tourette Syndrome
Tourette syndrome is a complex neuropsychiatric disorder with a wide phenotypic spectrum, including tics and psychiatric comorbidities, such as obsessive-compulsive disorder and attention-deficit disorder. Often considered a neurodevelopmental disorder, it is most prevalent during childhood and treatment strategies can vary according to degree of severity and patient-specific symptom manifestations. This review focuses on established and emerging management options for tics, including behavioral interventions and nonpharmacologic therapies, medication management, and promising surgical approaches. (Source: Neurologic Clinics)
Source: Neurologic Clinics - March 9, 2020 Category: Neurology Authors: Joohi Jimenez-Shahed Source Type: research
Medical, Surgical, and Genetic Treatment of Huntington Disease
Huntington disease, a neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, is caused by a CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. Current treatments target symptom management because there are no disease-modifying therapies at this time. Investigation of RNA-based and DNA-based treatment strategies are emerging and hold promise of possible future disease-modifying therapy. (Source: Neurologic Clinics)
Source: Neurologic Clinics - March 9, 2020 Category: Neurology Authors: Christine M. Stahl, Andrew Feigin Source Type: research
Treatment of Functional Movement Disorders
Functional movement disorders (FMD) are commonly seen in neurologic practice and are frequent sources of disability. Patients may present with tremor, weakness, dystonia, jerking movements, abnormal gait and speech, often combining several movement phenomenologies. Associated symptoms include chronic pain, depression, and anxiety. Treatment of FMD begins with an explanation of the diagnosis and needs to be tailored to patients ’ symptoms and comorbidities. There may be benefit from multidisciplinary treatment, including physical, occupational, and speech therapy, as well as psychotherapeutic interventions, especially...
Source: Neurologic Clinics - March 9, 2020 Category: Neurology Authors: Kathrin LaFaver Source Type: research
Medical and Surgical Treatments for Dystonia
The dystonias are a large and heterogenous group of disorders characterized by excessive muscle contractions leading to abnormal postures and/or repetitive movements. Their clinical manifestations vary widely, and there are many potential causes. Despite the heterogeneity, helpful treatments are available for the vast majority of patients. Symptom-based therapies include oral medications, botulinum toxins, and surgical interventions. For some subtypes of dystonia, specific mechanism-based treatments are available. Advances in understanding the biological basis for many types of dystonia have led to numerous recent clinical...
Source: Neurologic Clinics - March 2, 2020 Category: Neurology Authors: H.A. Jinnah Source Type: research
Current and Emerging Treatments of Essential Tremor
Established medications that improve tremor include beta-adrenergic antagonists, primidone, topiramate, and ethanol. Less consistent efficacy is reported with many other medications, usually antiepileptic drugs. A number of investigational medications, including T-type calcium channel blockers and allosteric gamma-aminobutyric acid-A modulators, are being developed for tremor. Deep brain stimulation techniques continues to be refined and focused ultrasound thalamotomy now offers an incisionless surgical option. Finally a number of peripheral electrical and mechanical devices are under development for tremor. (Source: Neurologic Clinics)
Source: Neurologic Clinics - February 28, 2020 Category: Neurology Authors: William George Ondo Source Type: research
Treatment of Tardive Dyskinesia
Tardive dyskinesia (TD) is an iatrogenic condition that encompasses a wide phenomenological spectrum of movement disorders caused by exposure to dopamine receptor blocking agents (DRBAs). TD may cause troublesome or disabling symptoms that impair quality of life. Due to frequent, often inappropriate, use of DRBAs, TD prevalence rates among patients exposed to DRBAs continue to be high. The judicious use of DRBAs is key to the prevention of TD, reduction of disease burden, and achieving lasting remission. Dopamine-depleting vesicular monoamine transporter type 2 inhibitors are considered the treatment of choice of TD. (Sour...
Source: Neurologic Clinics - February 28, 2020 Category: Neurology Authors: Hassaan H. Bashir, Joseph Jankovic Source Type: research
This article reviews the clinical pres entation, epidemiology, genetics, pathophysiology, diagnosis, and management of Wilson disease. (Source: Neurologic Clinics)
Source: Neurologic Clinics - February 28, 2020 Category: Neurology Authors: Caitlin Mulligan, Jeff M. Bronstein Source Type: research
An Overview of the Current State and the Future of Ataxia Treatments
Cerebellar ataxia can be caused by a variety of disorders, including degenerative processes, autoimmune and paraneoplastic illness as well as by gene mutations inherited in autosomal dominant, autosomal recessive, or X-linked fashions. In this review, we highlight the treatments for cerebellar ataxia in a systematic way, to provide guidance for clinicians who treat patients with cerebellar ataxia. In addition, we review therapies currently under development for ataxia, which we feel is currently one of the most exciting fields in neurology. (Source: Neurologic Clinics)
Source: Neurologic Clinics - February 27, 2020 Category: Neurology Authors: Kimberly Tsu Kwei, Sheng-Han Kuo Source Type: research
Surgical Treatment of Parkinson Disease
Surgery in Parkinson disease is effective for a select group of patients when optimal medical management is not sufficient. Functional neurosurgery can be used as either a salvage therapy in patients with disabling symptoms or to maintain quality of life and independence before progression to severe disability in high-functioning patients. With recent technological advancements in imaging and targeting as well as novel neuromodulation paradigms, there are numerous options for targeted brain lesions and deep brain stimulation. Surgical decision making and postoperative management in Parkinson disease therefore often require...
Source: Neurologic Clinics - February 22, 2020 Category: Neurology Authors: Kyle T. Mitchell, Jill L. Ostrem Source Type: research
Pharmacologic Treatment of Motor Symptoms Associated with Parkinson Disease
The cardinal motor features of Parkinson disease (PD) are driven by striatal dopamine deficiency. Pharmacologic dopamine substitution is the mainstay of drug treatment of PD. Levodopa is still the most efficacious drug to treat PD motor symptoms. MAO-B inhibitors and dopamine agonists are useful options. The main limitation of levodopa is the development of motor response fluctuations and drug-induced dyskinesias. Adjunct MAO-B and COMT inhibitors as well as dopamine agonists and continuous infusions of levodopa intestinal gel or subcutaneous apomorphine are efficacious in reducing motor fluctuations and amantadine is the ...
Source: Neurologic Clinics - February 20, 2020 Category: Neurology Authors: Werner Poewe, Philipp Mahlknecht Source Type: research
Treatment of Nonmotor Symptoms Associated with Parkinson Disease
This article discusses symptoms, assessments, and therapeutics for the nonmotor symptoms of PD including those affecting mood, cognition, behavior, sleep, autonomic function, and sensory systems. (Source: Neurologic Clinics)
Source: Neurologic Clinics - February 13, 2020 Category: Neurology Authors: Jennifer G. Goldman, Carlos Manuel Guerra Source Type: research
Clinical Rating Scales and Quantitative Assessments of Movement Disorders
This article reviews scales that have been developed for, validated in, and/or frequently used across multiple movement disorders with a focus on assessment of motor and nonmotor symptoms of Parkinson disease. Rating scales used in other disease states include those for essential tremor, dystonia (generalized dystonia, cervical dystonia, and blepharospasm), Tourette syndrome, Huntington disease, tardive dyskinesia, Wilson disease, ataxia, and functional movement disorders. Key features of each scale as well as cited criticisms and limitations of each scale are also discussed. Lastly, the article briefly discusses the emerg...
Source: Neurologic Clinics - February 4, 2020 Category: Neurology Authors: Arjun Tarakad Source Type: research
Neuroimaging for the Neurologist
MRI is a commonly used diagnostic tool in neurology, and all neurologists should possess a working knowledge of imaging fundamentals. An overview of current and impending MRI techniques is presented to help the referring clinician communicate better with the imaging department, understand the utility and limitations of current and emerging technology, improve specificity and appropriateness when ordering MRI studies, and recognize key findings. (Source: Neurologic Clinics)
Source: Neurologic Clinics - November 22, 2019 Category: Neurology Authors: Nandor K. Pinter, Joseph V. Fritz Source Type: research
Cranial Nerve Imaging and Pathology
This review provides a symptom-driven approach to neuroimaging of disease processes affecting the cranial nerves. In addition to describing characteristic imaging appearances of a disease, the authors emphasize exceptions to the rules and neuroimaging pearls. The focus is on adult neurology although some important pediatric conditions are included. On reviewing this material, the reader should be able to (1) differentiate intra- and extra-axial causes of cranial nerve dysfunction and (2) appropriately use neuroimaging to investigate abnormalities of cranial nerve function. (Source: Neurologic Clinics)
Source: Neurologic Clinics - November 22, 2019 Category: Neurology Authors: Zoltan Klimaj, Joshua P. Klein, Gabriella Szatmary Source Type: research
Imaging of Neurologic Disorders in Pregnancy
Pregnant women may have exacerbation of preexisting neurologic disorders or new-onset neurologic symptoms for which brain or spinal cord imaging is appropriate. Primary headaches in early pregnancy can be diagnosed and treated without imaging. Headaches later in pregnancy or in the peripartum period may need to be evaluated by brain and/or vascular imaging. Cerebrovascular complications have distinctive imaging but overlapping presentations. Mass lesions can enlarge, producing neurologic symptoms, late in pregnancy. Imaging may be necessary to diagnose neurologic disorders in pregnancy and the peripartum period. MRI is pre...
Source: Neurologic Clinics - November 22, 2019 Category: Neurology Authors: Dara G. Jamieson, Jennifer W. McVige Source Type: research
Neuroimaging of Deep Brain Stimulation
This article discusses how imaging improves surgical techniques and outcomes and widens possibilities in translational neuroscience in Parkinson disease, essential tremor, generalized dystonia, and epilepsy. In movement disorders diffusion tensor imaging allows anatomic segment of cortical areas and different functional subregions within deep-seated targets to understand the side effects of stimulation and gain more data to describe the therapeutic mechanism of action. The introduction of visualization of white matter tracks increases the safety of neurosurgical techniques in functional neurosurgery and neuro-oncology. (So...
Source: Neurologic Clinics - November 22, 2019 Category: Neurology Authors: Lorand Eross, Jonathan Riley, Elad I. Levy, Kunal Vakharia Source Type: research
Transcranial Doppler ultrasonography (TCD) is a noninvasive, bedside, portable tool for assessment of cerebral hemodynamics. Modern TCD head frames allow continuous hands-free emboli detection for risk stratification and assessment of treatment efficacy in several cardiovascular diseases. Identifying a focal stenosis, arterial occlusion, and monitoring the treatment effect of intravenous tissue plasminogen activator can easily be accomplished by assessing TCD waveforms and determining prestenotic and poststenotic mean flow velocities. TCD is an excellent screening tool for vasospasm in aneurysmal subarachnoid hemorrhage. T...
Source: Neurologic Clinics - November 22, 2019 Category: Neurology Authors: Ryan Hakimi, Andrei V. Alexandrov, Zsolt Garami Source Type: research