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Lambert-Eaton Myasthenic Syndrome



Keywords


Lambert-Eaton syndrome, neuromuscular junction, neuromuscular disease


Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Antibodies directed at the voltage-gated calcium channels (VGCCs) on presynaptic cholinergic nerve terminals are responsible for the disease. Calcium entry via VGCCs is required to facilitate vesicle docking and release of presynaptic acetylcholine (ACh). Antibodies to P/Q type VGCCs lead to a reduction in the release of presynaptic ACh vesicles. Presynaptic ACh stores and the postsynaptic response to individual quanta are normal.


LEMS is a rare disease that typically occurs after age 40 in males and females with near equal incidence. LEMS is often the result of a paraneoplastic phenomenon, the symptoms of which may or may not precede detection of an underlying malignancy, of which more than 80% is small-cell lung cancer. Other neoplasms associated with LEMS include leukemia and carcinomas of the rectum, kidney, stomach, and breast. LEMS may occur in the absence of cancer and is not uncommonly associated with other autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome.


Clinical features


Clinical features include proximal leg or arm weakness; muscle aching and stiffness worsened by prolonged exercise; and difficulty with certain movements, such as combing hair or rising from a chair. Unlike myasthenia gravis (MG), ocular and bulbar symptoms are rare but may occur. However, transient diplopia, ptosis, dysphagia, dysarthria, and neck flexion weakness can develop in later stages. Autonomic involvement is common and characterized by xerostomia, xerophthalmia, erectile dysfunction, postural hypotension, and constipation. Sensory complaints are rare.


On examination, proximal weakness of the lower limbs greater than the upper limbs is the most consistent finding. A progressive increase in strength after a few seconds of sustained contraction is usual, with fatigue after continued contraction. Muscle wasting is rare. Limb reflexes are decreased or absent in over 90% of cases. However, a potentiation of reflexes after maximal contraction of the involved muscle for 10 to 15 seconds may be present.


Laboratory findings


Nerve conduction studies typically demonstrate low compound muscle action potential (CMAP) amplitudes of < 50% the lower limit of normal, which increase with 20 to 50 Hz repetitive nerve stimulation or 10 seconds of maximum sustained voluntary muscle contraction (post-exercise facilitation of > 100%) due to calcium accumulation in the presynaptic terminal with subsequent enhancement of ACh vesicle release. Sensory responses, nerve conduction velocities, and latencies are normal. Slow repetitive stimulation (2 Hz) produces a decremental response of the CMAP amplitude similar to MG. Antibodies to VGCCs can be tested in blood but their absence in early disease may give cause for repeat testing. The majority of patients with cancer-associated LEMS will have antibodies against SOX1.


Treatment


Treatment is directed at the responsible tumor or underlying autoimmune disorder. 3,4-diaminopyridine (3,4-DAP) and intravenous immunoglobulin (IVIg) have been demonstrated to improve muscle strength. 3,4-DAP inhibits voltage-gated K + channels which prolongs the presynaptic action potential, thereby allowing more Ca2 + channels to open, resulting in increased [Ca2 +] at the nerve terminal. 3,4-DAP doses range from 5 to 25 mg three times per day/ four times per day and there may be a synergistic effect with pyridostigmine (30–60 mg three times per day/ four times per day), which is an acetylcholinesterase inhibitor. IVIg and plasmapheresis may provide short-term improvement and serve as rescue therapy although responses tend to be less dramatic than with MG. If these treatments are ineffective then consideration of corticosteroids and/or steroid-sparing immunomodulators such as azathioprine, cyclosporine, and rituximab is warranted.


Prognosis for non-cancer-associated LEMS is good; however, life-long therapy is generally required. Prognosis of cancer-associated LEMS is largely related to prognosis of the underlying malignancy.



Learning Disabilities



Keywords


Learning disability, dyslexia, reading, math, social skills, childhood


A learning disability (LD) is a neurological disorder presenting as difficulty in the acquisition and use of language, reading, mathematical abilities, or social skills in a patient with otherwise normal intelligence, that has persisted for at least 6 months, despite the provision of interventions that target those difficulties. The prevalence of LD is 5% to 15% among school-age children across different languages and cultures. Prevalence in adults is unknown but has been estimated as 4%.


Learning disabilities can also interfere with higher-level skills such as organization, time planning, abstract reasoning, long or short memory, and attention. It is important to realize that learning disabilities can affect an individual’s life beyond academics and can impact relationships with family, friends, and in the workplace. Approximately 50% of children with LD have associated attention deficit hyperactivity disorder (predictive of worse mental health outcome), conduct disorder, anxiety disorders, and mood disorders. School dropout and co-occurring depressive symptoms increase the risk for poor mental health outcomes, including suicidality, whereas high levels of social or emotional support predict better mental health outcomes.


Dyslexia is the most common LD (80%). Dyslexia is a chronic condition in which there is impaired ability to break down words into their basic phonologic parts, resulting in difficulties in decoding and identifying the words. This will often present in a child having difficulty learning to read, and often persists into adulthood.


In pre-schoolers, LD usually becomes evident as language delay. A child who has no meaningful words by age 18 months, no meaningful phrases by age 24 months, or speech unintelligible to strangers by age 3 years should be evaluated for hearing loss and referred for speech therapy evaluation. In school-age children, LD usually becomes evident as unexpected school difficulty or failure. Manifestations may be behavioral (e.g., a reluctance to engage in learning; oppositional behavior); adults may avoid activities that demand arithmetic or reading. There is often a family history of learning problems. Prematurity or very low birth weight increase the risk for specific learning disorders, as does prenatal exposure to nicotine. Psychometric evaluation should be administered to children with school performance difficulties to verify normal intelligence and failure to achieve the expected level of performance. LD may not manifest fully until later school years, by which time learning demands have increased and exceed the individual’s limited capacities.


In the United States, the clinician should assure parents that, under the Individuals with Disabilities Education Act, public schools are mandated to meet the educational needs of all developmentally disabled children. This act further mandates the proper assessment of educational needs (including psychometric testing) and enactment of an individual education plan (IEP). All of this assessment should be performed in a timely fashion.


Counseling for associated social, behavioral, and psychiatric symptoms should be tailored to the child’s specific deficit. Parent support and consultation can help the family develop a supportive home environment and a behavioral reinforcement program.

Aug 12, 2020 | Posted by in NEUROLOGY | Comments Off on L
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