Neuromuscular Junction Disorders Research Articles

Electrophysiological study in neuromuscular junction disorders

This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG) helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS). SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.

Occupational Neurotoxic Diseases in Taiwan

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

The Epidemiologic, Clinical and Laboratory Findings of Patients with Myasthenia Gravis in Southern Iran

Introduction: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular junction associated with presence of antibodies against nicotinic acetylcholine receptors (nAChRs). The pattern of the MG varies in different ethnical and geographical regions. Data regarding the pattern of the disease in Iran is scarce. Thus we performed this study in order to describe the epidemiologic, clinical and laboratory characteristics of MG in Iranian population. Method and Material: This was a retrospective study being performed in Nemazee Hospital, a tertiary health care center affiliated with Shiraz University of Medical Sciences, from 2001 to 2010. The medical records were reviewed and the data were entered into a computer database. Data are presented as mean ± SD and proportions as appropriate. Result: Overall we included 208 patients with MG among whom there were 62 (29.8%) men and 146 (70.2%) women. The mean age of the patients was found to be 33.19 ± 15.75 (range 1-85) years. The median age at onset was 28±2.3 years. Eight (3.9%) patients had family history of MG, 1.9% and 2.4% of patients had a background of Diabetes Mellitus and Rheumatoid disease in family, respectively. Thymoma was observed in 9.1% of patients. The presenting symptom was found to be ocular ones detected in 67 (34.9%) patients out of which 59 (30.7%) had bulbar and 12 (6.3%) had appendicular involvement. Edrophonium test was done for 28 patients out of whom 78.6% tested positive. The most common histopathology finding was thymic hyperplasia and the second most common was thymoma. Conclusion: This is the first study describing MG in an Iranian population. The pattern of disease was found to be much more similar to North America and Europe. MG was found to be more common in females consistent with western studies. [GMJ. 2012;1(1):20 -23]

Chronic Inflammatory Demyelinating Polyneuropathy Presenting with Recurrent Ataxia, Bulbar Weakness, and Respiratory Dysfunction (P06.135)

Objective: To report a case of chronic inflammatory demyelinating polyneuropathy in a patient presenting with recurrent bouts of ataxia, bulbar weakness, and respiratory dysfunction. Background Chronic inflammatory demyelinating polyneuropathy (CIDP) can have a variable presentation leading to delay in diagnosis and treatment. We present a case of a 55-year-old man with recurrent bouts of ataxia and bulbar weakness as his initial presentation of CIDP. Design/Methods: A literature search was performed to look for comparable reports. Results: A 55-year-old diabetic man developed progressive ataxia, fatigue, dysarthria and dysphagia over a six-month period. He then presented to the hospital with acute bilateral upper extremity weakness and respiratory distress requiring intubation. He was found to be areflexic except at the biceps tendon and had difficulty weaning the ventilator. An MRI of the brain as well as initial CSF studies were normal. The patient was presumed to have a variant of Guillain-Barre syndrome and was treated empirically with plasmapheresis. He improved and was extubated. He went on to develop neck extensor weakness, followed by two further episodes of ataxia and respiratory failure at 6 and 9 months thereafter. Each time, he was treated with plasmapheresis and improved. Repeat CSF analysis at 9 months showed 1 RBC, 2 WBCs, 92 glucose, and 60 protein. Complete metabolic, autoimmune, infectious, and paraneoplastic workup was negative. Anti-GQ1b antibodies were negative. Acetylcholine receptor and anti-musk antibodies were negative. Nerve conduction study showed mild to moderate, motor and sensory, mixed axonal and demyelinating polyneuropathy. EMG showed evidence of denervation/reinnervation changes. Single fiber EMG demonstrated mildly increased jitter, though not in the neuromuscular junction disorder range. The patient was started on prednisone and is currently doing well. Conclusions: Chronic inflammatory demyelinating polyneuropathy can have a variable presentation and should be considered in patients with recurrent, unexplained ataxia and bulbar weakness. Disclosure: Dr. Malka has nothing to disclose. Dr. Muntean has nothing to disclose.

Clinical Reasoning: A middle-aged woman with progressive symmetric weakness and a CSF pleocytosis

A 54-year-old Ecuadorian American woman presented with 4 days of progressive bilateral extremity weakness, which began in the upper extremities but quickly spread to the lower extremities. The patient also reported reduced gait stability, bilateral distal paresthesias, and patchy decreased sensation with pain over her lower abdomen and pelvis. At presentation, she denied symptoms of dysautonomia or bulbar dysfunction. Past medical history included longstanding rheumatoid arthritis treated with chronic methylprednisolone, hypertension, left sciatic radiculopathy, scoliosis, uterine prolapse, and thyroid disease. On examination, the patient's vitals were stable. Mental status and cranial nerves were normal. Motor strength was decreased symmetrically in the upper and lower extremities (4/5) with areflexia and absent plantar reflexes. The patient had decreased pinprick sensation over the T6–T8 dermatomes and diminished vibratory sense distally. Joint position sense was preserved bilaterally. The patient demonstrated a paraparetic slow gait with assistance. ### Questions for consideration: 1. What is the differential diagnosis? How does the presence of both sensory deficits and motor involvement narrow the differential? 2. What is the next step in management for this patient? What additional testing would you order? An acute inflammatory neuropathy or cervical myelopathy were top on the differential diagnosis. Neuromuscular junction disorders and myopathies were considered less likely due to the patient's sensory involvement. Infectious etiologies, such as Lyme disease and HIV, were also considered and tested in the serum and CSF. To exclude a myelopathic process, x-rays of the cervical and lumbar spine were initially performed and showed no evidence of subluxation or fracture. An MRI spinal survey was significant for compound scoliosis of the lower thoracic and lumbar spine, multilevel disc bulges, and mild enhancement of the cauda equina. However, neither intramedullary lesions …

MuSK myasthenia gravis and Lambert–Eaton myasthenic syndrome in the same patient

Myasthenia gravis is an organ-specific autoimmune disorder of he neuromuscular junction caused by antibodies against acetylholine receptor (AChR) in 70–94% of patients. In 30–50% of emaining “seronegative” MG patients antibodies against the musle specific tyrosine kinase (MuSK) are found [1,2]. It has been hown that MuSK is essential for the agrin-mediated clustering f AChR during development of neuromuscular junction [1]. The roup of MuSK patients is distinguished from AChR-Ab positive MG atients by a specific clinical phenotype, electrophysiological and mmunological features, and they respond less well to immunouppressive therapy [1,2]. Lambert–Eaton myasthenic syndrome (LEMS) is also an autoimune disease of the neuromuscular junction, but, contrary to MG, he defect of transmission is of presynaptic type [3]. In about 0–70% of patients LEMS is a paraneoplastic disease (P-LEMS), ostly associated with a small-cell lung carcinoma (SCLC), while n the other group of the patients it is a pure autoimmune disease NP-LEMS) and is associated with other autoimmune disorders, resenting in the form of “overlap syndromes”. In both types

A Case of Lambert-Eaton Myasthenic Syndrome with Small-Cell Lung Cancer and Transient Increase in Anti-Acetylcholine-Receptor-Binding Antibody Titer

BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder that is most frequently associated with small-cell lung cancer (SCLC). The titers of antibodies against voltage-gated calcium channels are frequently increased in LEMS, but only rarely is titer of anti-acetylcholine-receptor-binding antibodies (AChR-abs) increased.Case ReportA 57-year-old male was admitted to our hospital due to dry mouth and eyes and progressive proximal limb weakness of 2 months duration. The results of a repetitive nerve stimulation test disclosed all criteria for the electrophysiological LEMS pattern, and the patient's AChR-abs titer was 0.587 nmol/L. At a follow-up performed 5 years after successful treatment of SCLC and LEMS, his AChR-abs titer had decreased to 0.001 nmol/L.ConclusionsWe suggest that this was a case of transient pseudopositivity of AChR-abs in SCLC with LEMS.

Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).

Stromal cell derived factor-1 genetic variation at locus 801 in patients with myasthenia gravis.

Myasthenia gravis (MG) is the most common disorder of neuromuscular junction in which autoantibodies develop against nicotinic acetylcholine receptor for unknown reasons. The association of immunomodulator genes with different autoimmune disease has been studied in recent years. The aim of this study was to investigate correlation between a genetic variation in Stromal Cell Derived Factor-1 (SDF1) and susceptibility to MG in an Iranian population. Genotyping of SDF1 at position 801 G/A was performed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) in 87 patients with confirmed myasthenia gravis and 261 normal control subjects. No statistically significant differences were observed in the frequencies of genotypes and alleles between patients and controls (p>0.05). Furthermore, no significant differences in the genotype distribution were found between the cases with different stages (p>0.05). Our data suggest that the SDF1 gene polymorphism at position 801 G/A is not associated with myasthenia gravis.

Case report: a case review of Lambert-Eaton myasthenic syndrome and low back pain.

The following is a case report which reviews the essential aspects of Lambert-Eaton myasthenic syndrome (LEMS) in a patient with long standing back pain and gait dysfunction. The patient was referred to our electrodiagnostics laboratory for a 9-month history of low back pain and difficulty walking following a charity breast cancer walk. A workup including magnetic resonance imaging of the brain, entire spine, and EMG/NCS at another institution were reportedly normal. A detailed history revealed symptoms of proximal weakness and autonomic dysfunction. Physical findings were consistent with proximal weakness, a bilateral gluteus medius gait, and diffusely absent reflexes obtainable in the biceps after 3s of contraction. Electrical testing revealed an initial low compound muscle action potential amplitude in the deep peroneal nerve recording from the extensor digitorum brevis. Repetitive stimulation at 2Hz revealed a decremental response of 42% from the 1st response to the 4th response. Following 3s of exercise, the amplitude increased by 300%. After 30s of exercise followed by 1min of rest, there was a return of the decremental response. The history, physical examination, and electrical findings were illustrative of a presynaptic neuromuscular junction disorder, specifically LEMS.

Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10%) (1). Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2 cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2). Myasthenia gravis (MG) is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR). MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3). No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour.

Bilateral cavernous sinus syndrome and bilateral cerebral infarcts: A rare combination after wasp sting

Neurologic manifestations of wasp sting are uncommon and delayed in onset (Sachdev et al. [1]). Various central and peripheral nervous system presentations have been described including wasp sting encephalopathy, cerebral infarction, optic neuropathy, polyradiculopathy, neuromuscular junction disorders, etc [1]. Cerebral infarction is a rare manifestation and sequential bilateral hemiparesis has been reported in only one case (Riggs [2]). We report a case of a young boy presented with bilateral cavernous sinus thrombosis with bilateral cerebral infarcts, a rare combination.

Polymorphisme clinique de la myasthénie à point de départ oculaire ; analyse rétrospective sur cinq ans

myasthenia gravis is a neuromuscular junction disorder that can jeopardize the patient's life and has a high clinical polymorphism that makes it difficult to diagnose. after reviewing the disease physiology, its clinical symptoms, and the different means to diagnose and treat it, we present a 15-patient series that we cared for at the Rothschild ophthalmologic foundation from 2002 to 2007 for myasthenia gravis that began with isolated ocular symptoms, so as to highlight the clinical diversity of this pathology. when the disease was diagnosed, 11 patients out of 15 had a ptosis with diplopia, two had an isolated ptosis, and two had isolated diplopia. After investigations, we discovered that three patients had a malignant thymoma and one had thymic hyperplasia. An autoimmune disease association was found in two patients: the first one had Hashimoto thyroiditis and the second one developed optical neuromyelitis a few years after his myasthenia gravis. Only three patients secondarily developed a generalized myasthenia gravis. our series of patients has a low disease generalization rate in comparison with the published data in the medical literature, indicating that two-thirds of patients with ocular myasthenia gravis should develop generalized myasthenia gravis within approximately 2 years after the beginning of their illness. This could be explained by the early consultation of these patients and the common prescription of an immunosuppressive therapy, reducing the risk of secondarily generalized myasthenia gravis according to some studies. despite the small number of patients, this study underlines the clinical polymorphism of ocular myasthenia gravis and the risks it may cause. Close collaboration between ophthalmologists and neurologists is needed to ensure good care for these patients.

Isolated dysphagia due to paraneoplastic myasthenic syndrome with anti-P/Q-type voltage-gated calcium-channel and anti-acetylcholine receptor antibodies

Dysphagia is a common symptom in neuromuscular junction disorders, but it rarely occurs in isolation or is the presenting feature. We describe a patient presenting with isolated dysphagia to liquids. Electrophysiological studies, such as repetitive nerve stimulation and single-fiber electromyography, were normal. Serum anti-P/Q-type voltage-gated calcium-channel (anti-P/Q-type VGCC) and anti-acetylcholine receptor (AChR ab) antibodies were above the normal range. A computed tomography scan showed a mediastinal mass corresponding to a thymic carcinoma. After chemotherapy, surgical removal of the thymic carcinoma and radiotherapy, the patient no longer complained of dysphagia, AChR ab titers were reduced and anti-P/Q-type VGCC antibodies became negative. To the best of our knowledge, no previous reports of a paraneoplastic myasthenic syndrome related to thymic carcinoma with both anti-P/Q-type VGCC and AChR antibodies have been described.

Approach to acute or subacute myelopathy

Improved understanding of the differential diagnosis and improved investigative techniques, particularly neuroimaging and serologic testing, have facilitated the diagnosis of patients with acute and subacute myelopathy and reduced the proportion of patients who are labeled as having “idiopathic transverse myelitis.” Additionally, these advances have identified subgroups of patients in whom progression of deficit or future relapses are anticipated, allowing intervention and prophylaxis as appropriate. However, early management remains empiric and consists of high-dose corticosteroids for most patients. In the event of an inadequate response to corticosteroids or a subsequent atypical course, further investigations to detect diagnoses other than “transverse myelitis” should be considered and additional treatments, such as plasmapheresis, may be appropriate. Individualized diagnosis and treatment is more feasible now than in the past. Localizing an acute neurologic process to the spinal cord is often, but not always, straightforward (table 1). The ascending sensory symptoms of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) may confuse the diagnosis, as this complaint is also highly associated with acute myelopathy. Unequivocal upper motor neuron signs exclude AIDP, but are often not apparent in the early stages of a spinal cord insult. Although not invariably present, an unequivocal sensory level on the torso, sensory loss indicating involvement of spinal tracts (e.g., spinothalamic modality impairment contralateral to motor findings), or urinary retention localize to the spinal cord. Myopathy or neuromuscular junction disorders may be mistaken for myelopathy, particularly if the lower limbs are predominantly affected, but the absence of any sensory abnormality should suggest the correct localization. Bilateral mesial frontal lobe lesions (e.g., bilateral anterior cerebral artery distribution infarcts) could mimic a myelopathy, although abulia or other signs of frontal lobe dysfunction typically coexist. Autoimmune or paraneoplastic muscle stiffness syndromes, such as stiff-person syndrome associated with glutamic acid decarboxylase or amphiphysin autoantibodies, may be confused with spasticity …

Therapy update in nerve, neuromuscular junction and myopathic disorders

The objective of this review is to summarize recent advances in the treatment of various neuromuscular disorders including neuropathies, neuromuscular junction disorders, and myopathies. Immunotherapy with sophisticated agents for myasthenia gravis and inflammatory myopathies, neuroprotection with vitamin E for chemotherapy-induced neuropathy, and promising gene transfer and exon-skipping therapies for muscular dystrophy are among the most exciting recent developments in the treatment of neuromuscular disorders. In spite of significant advances, therapy in many neuromuscular diseases remains far from satisfactory. Better understanding of the underlying molecular and pathophysiologic processes for both hereditary and acquired disorders should lead to more refined and successful therapeutic approaches, reducing physical and other types of disability while posing fewer side effects.

Index Of Suspicion In The Nursery

A male infant who has trisomy 21 is born large for gestational age at 36 weeks' gestation to a 40-year-old G4P2 mother. The mother experienced gestational diabetes and hypertension during the pregnancy. The hospital course in the neonatal intensive care unit (NICU) is uneventful. The infant consumes human milk supplemented with formula every 3 hours. Due to decreased intake, nutritional supplementation by nasogastric tube is initiated. He requires 25 to 30 minutes to feed by mouth with chin support and pacing. There is minimal emesis with feedings until 9 days after birth, when he begins vomiting with each feeding. The amount of emesis varies, consists of undigested milk, and is otherwise nonbilious and nonbloody. The infant can tolerate only small amounts of his feedings by either mouth or nasogastric tube before vomiting, but he continues to have two to three bowel movements per day and good urine output. On physical examination, the baby has physical features consistent with trisomy 21, including epicanthal folds, a flat nasal bridge, macroglossia, Brushfield spots, widened space between the first and second toes, single palmar creases, and generalized hypotonia. There is no notable abdominal distention or palpable abdominal masses. The remainder of the examination yields normal results. A radiologic study helps to reveal the diagnosis. A term male infant is admitted to the NICU after difficulty feeding and respiratory distress at 5 hours of age. The baby was born to a 35-year-old G3T2P0A0L2 woman. All maternal laboratory results were negative during prenatal screening, although prenatal ultrasonography during the third trimester showed oligohydramnios and intrauterine growth restriction. The initial evaluation after delivery revealed an asymmetric, small-for-gestational age infant whose birthweight was 2,215 g and Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. On physical examination, the infant exhibited generalized hypotonia, poor suck …

Structure-Activity Relationship of Quaternary Acetylcholinesterase Inhibitors – Outlook for Early Myasthenia Gravis Treatment

Myasthenia gravis is a rare autoimmune neuromuscular junction disorder mainly caused by antibodies being targeted against the muscle acetylcholine receptors (AChRs). The loss of AChRs leads to a defect in neuromuscular transmission resulting in muscle weakness and fatigue. Although once an often fatal illness, Myasthenia gravis can now be well managed with relatively safe and effective treatments. However, the severe myasthenic cases associated with thymus tumors remain often fatal exception in the management of the disease. The early treatment includes the use of acetylcholinesterase inhibitors (AChEI) which enhance neuromuscular transmission. To ensure a peripheral effect, charged molecules are used, particularly quaternary ammonium salts. The structure of AChEIs has been continuously modified to obtain the optimal ratio between AChE inhibition and potential side-effects. This review summarizes progress in the use of quaternary compounds as AChE inhibitors in vitro with respect to their structure and inhibitory ability. Namely, carbamic acid esters, piperidinium and pyridinium salts, bisquaternary pyridinium salts and heterogeneous quaternary inhibitors are all discussed. Among data found in the literature, many compounds have shown promising inhibition of AChE when compared to commercial standards (pyridostigmine, neostigmine). Besides a promising inhibitory ability, selectivity for AChE versus butyrylcholinesterase (BChE) for the most potent compounds (sub-nanomolar IC(50)) was also identified.

Autoimmune Channelopathies: Well-Established and Emerging Immunotherapy-Responsive Diseases of the Peripheral and Central Nervous Systems

The role of antibodies in neuromuscular junction disorders is well established with antibodies to acetylcholine receptor, muscle-specific kinase, and voltage-gated calcium channels. The diseases associated with these antibodies, myasthenia gravis and the Lambert-Eaton myasthenic syndrome, respond well to symptomatic treatments (e.g., cholinesterase inhibitors) and to immunotherapies such as plasma exchange, intravenous immunoglobulin, oral steroids, and steroid-sparing drugs. The role of the antibodies has been established by a variety of in vitro and in vivo approaches. More recently, antibodies to voltage-gated potassium channels have been identified in patients with autoimmune forms of acquired neuromyotonia. Over the last decade, antibodies to CNS membrane receptors or ion channels have begun to be identified and these antibodies define antibody-mediated CNS diseases that also respond to immunotherapies. The paradigms gained from the study of the peripheral conditions has led to a better appreciation of the role of antibodies in neurological disorders and a growing recognition of their role in central nervous system (CNS) diseases.

Carpal Tunnel Syndrome After Ciprofloxacin-Induced Tendinitis

To the Editor: Different types of antibiotics can affect the peripheral nervous system and cause neuropathies, myopathies, and neuromuscular junction disorders by direct or indirect mechanisms.1 Fluoroquinolones may also cause seizures or encephalopathy, and a few cases of tendinitis have been reported as well.2-4 Tendinitis may occur as early as 2 hours after the first dose, and 50% of patients develop symptoms within 6 days of starting medication. Tenosynovitis has also been reported in association with recurrent carpal tunnel syndrome.5 We report a case of ciprofloxacin-related tendinitis leading to carpal tunnel syndrome A 77-year-old right-handed woman developed a urinary tract infection and was empirically treated with oral ciprofloxacin. Three days later, she developed bilateral hand pain and swelling, which improved after the medication was stopped and with a brief course of oral steroids and antihistamines. Symptoms were consistent with flexor tendinitis with focal tenderness and swelling. There was no history of diabetes, gout, rheumatoid arthritis, or of other autoimmune diseases. Because severe pain persisted waking her up, she was referred to a neurologist. At that time, 4 weeks after the onset and swelling resolved, the pain still involved the first three fingers, more severely on the left. She performed her daily activities independently, but pain got worse when these fingers were touched. She denied any neck or upper arm discomfort. On examination, she had slight atrophy and weakness of left thenar muscles (Medical Research Council 5-/5) with decreased sensation over distal aspects of the first three fingers on the left and left thenar allodynia. The remainder of the examination was normal. Electrodiagnostic testing was performed at 6 weeks after the onset and confirmed the diagnosis of bilateral distal median nerve entrapments (carpal tunnel syndrome) (Table 1), more severe on the left. Needle examination showed only few fibrillation potentials in the left abductor pollicis brevis muscle. The use of a wrist splint did not alleviate the symptoms. Repeat study 3 months later did not show significant improvement. Because symptoms persisted, she underwent bilateral sequential carpal tunnel releases resulting in resolution of her symptoms. Flexor tendinitis and inflammatory arthritis can precipitate median nerve entrapment in a confined space of carpal tunnel. Increased incidence of tendonitis has been described in elderly (older than 60 years of age) and with renal dysfunction or corticosteroid treatment.2-4 Most commonly, Achilles and patellar tendons are affected, but few cases of shoulder and hand tendinitis were reported. 2,3 Tendon rupture was reported in 5% of patients with quinolone-related tendinitis.2 Timely discontinuation of ciprofloxacin in our patient probably prevented tendon rupture and more significant nerve injury. Asymmetry of median nerve entrapments with more severe findings on the left in our case may be attributable to asymmetric tendinitis or possible pre-existing nerve entrapment aggravated by inflammation. Therefore, we should consider drug-induced tendinitis as a potential cause of musculoskeletal pain after institution of fluoroquinolone therapy. A recent report indicates that fluoroquinolones may also precipitate painful small fiber neuropathy expanding the spectrum of their toxicity.6 Early recognition of possible toxicity is crucial to stop the offending agent, avoid exercise, and hopefully reduce morbidity of fluoroquinolone-induced tendinitis.