The myasthenic syndrome after chloroquine

The author presents a case of a 52-year old woman who suffered from dermatitis seborrhoica. She was treated with chloroquine. During the third month of treatment with chloroquine the symptoms of myasthenia appeared and led to hospitalization. The neurological and additional examinations confirmed the diagnosis. Four days after withdrawal of chloroquine treatment the myasthenic symptoms began to disappear and they finally ceased after two weeks. At this all other drugs were also withdrawn. The control examination after two months showed normal neurological status.     

Highlights in muscle relaxants

The aim of this article is to provide an overview on neuromuscular blocking agents and a rational selection of the most appropriate agents, along with pharmacological and pharmacoeconomic considerations on neuromuscular blockers and their antagonists. Neuromuscular blocking agents are used during anesthesia to facilitate endotracheal intubation and provide surgically required paralysis. There is continuing development in the field of neuromuscular blocking agents, with new products appearing at regular intervals. All new agents come at increased costs. The proportion of anesthesia-related drug costs on a per-patient basis are small and vary from country to country, but account for no more than 12% of hospital drug budgets. However, given the large number of anesthetics performed over time, the total cost is significant. Moreover, such costs should be put into the perspective of the operating theater and patient admission costs. Appropriate selection of neuromuscular blocking agents can help not only to reduce biological costs secondary to complications, but also to make operating lists proceed smoothly and without incident. The paucity of outcome studies in relation to anesthetic drugs is not surprising given that anesthesia is used to facilitate the provision of therapy rather than being therapeutic in its own right. Accordingly, the assessment of anesthetic drugs has a different priority to therapeutic drugs. As anesthetic drugs are nontherapeutic, it is also difficult to determine the best choice of agent. However, new neuromuscular blocking agents are marketed on the basis of improvements in the frequency of side effects, safety, reliability, duration, reversibility and undesirable hemodynamic effects.     

Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an idiopathic or paraneoplastic syndrome producing antibodies against presynaptic voltage-gated P/Q calcium channels. This decreases calcium entry into the presynaptic terminal, which prevents binding of vesicles to the presynaptic membrane and acetylcholine release. LEMS is most often associated with small cell lung cancer, although idiopathic presentations comprise approximately 40% of the cases. The most common initial complaint is proximal muscle weakness involving the lower extremities more than the upper extremities. Depressed deep tendon reflexes and autonomic dysfunction are frequently present. Involvement of the bulbar or respiratory muscles is rare. Diagnosis is confirmed by electrophysiological testing, which demonstrates small compound muscle action potentials and facilitation with exercise or 20-Hz repetitive stimulation. A serum test for voltage-gated calcium channel antibodies is commercially available. Treatment involves removing the cancer associated with the disease. If cancer is not found, immunosuppressive medications and acetylcholinesterase inhibitors are used with moderate success. Patients with idiopathic LEMS should be screened every 6 months with chest imaging for cancer.     

Lambert-Eaton myasthenic syndrome

The Lambert-Eaton Myasthenic Syndrome (LEMS) is characterised by proximal muscle weakness initially affecting gait, autonomic symptoms (dry mouth, constipation, erectile failure), augmentation of strength during initial voluntary activation, and depressed tendon reflexes with post-tetanic potentiation. The disorder is paraneoplastic (small cell lung cancer) in about 60p. cent (P-LEMS); no cancer is associated in the remainder (NP-LEMS). LEMS affects all races. NP-LEMS can occur in childhood as well as adult life; P-LEMS is unusual at<30 Years. The weakness results from a reduction in the quantal release of acetylcholine from motor nerve terminals, caused by autoantibodies to P/Q-type voltage-gated calcium channels (VGCCs) that are provoked by tumour VGCCs in P-LEMS; the stimulus in NP-LEMS is not known. These antibodies may be implicated in the rarely associated cerebellar degeneration. The diagnosis can be confirmed by detecting the specific antibody in a radioimmunoprecipitation assay, and by finding a reduced compound muscle action potential amplitude that increases by>100p. cent following maximum voluntary activation. Most patients benefit from 3,4-diaminopyridine; pyridostigmine is less effective. Specific tumour therapy in P-LEMS will often ameliorate the neurological disorder. In those with severe weakness, IVIg or plasmapheresis confers short-term benefits. Prednisone alone or combined with azathioprine or cyclosporin can achieve long-term control of the disorder.     

Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction, and approximately 60% of patients with LEMS have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical data of Japanese patients in the present study are as follows: the ratio of men to women is 3: 1 (mean age, 62 years; age range, 17-80 years). Of the patients with LEMS, 61% have SCLC, whereas the others do not have cancer. Clinical symptoms are usually characterized by proximal muscle weakness and dysautonomia. In less than 10% of the patients, there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS), and these are usually associated with SCLC. The diagnosis can be confirmed by detecting a specific antibody in a radioimmunoprecipitation assay and finding reduced amplitude of compound muscle action potential that increases by over 100% after maximum voluntary activation or 50Hz of nerve stimulation. The pathomechanism of LEMS is characterized by impaired transmission across the neuromuscular junction because of autoantibodies directed against the presynaptic P/Q-type voltage-gated calcium channels (P/Q-VGCCs). Histopathologic evaluation of the cerebellum in patients with PCD-LEMS showed a reduced number of P/Q-type VGCCs in the molecular layer. Therefore, it was hypothesized that P/Q-VGCC antibodies may induce cerebellar dysfunction after entering the CNS in patients with PCD-LEMS. Specific tumor therapy in patients with LEMS as well as cancer often improves the neurologic deficit. Tumor removal is the primary treatment for LEMS. If the result of the primary screening is negative, screening should be repeated after 3-6 months and thereafter every 6 months for up to 2 years. Most patients benefit from 3, 4-diaminopyridine administered with pyridostigmine. In those with severe weakness, intravenous gamma globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone when administered alone or in combination with immunosuppressive drugs can achieve long-term control of the disorder.     

Lambert-Eaton myasthenic syndrome

This review of the Lambert-Eaton myasthenic syndrome (LEMS) emphasizes electrodiagnosis and includes a case report. A 50-year-old woman had become progressively weaker over 1.5 years. The suspected diagnosis was confirmed by the clinical electrophysiological findings and was made 6 months before the patient's oat-cell carcinoma was found. After treating with local radiation and chemotherapy, the myasthenic syndrome went into remission as the pulmonary lesion resolved.     

Congenital myasthenic syndrome: presentation, electrodiagnosis, and muscle biopsy

We report 10 children with congenital myasthenic syndromes diagnosed by clinical features, electrodiagnostic studies, and response to acetylcholinesterase inhibitors. Age at diagnosis (mean = 4.4 years; range 0.2-10 years) correlated with age fatigue was recognized. Symptoms at presentation included mild gross motor development delay (7/10), speech articulation difficulty (5/10), and respiratory and feeding difficulties resulting in poor growth in 7 of 10 children. None of the five children with possible presynaptic abnormalities had decremental compound muscle action potential responses to 2 Hz repetitive nerve stimulation. Instead, electrodiagnostic studies showed a more than 100% increment of compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation in two children and sustained compound muscle action potential decrement to 2 Hz repetitive nerve stimulation after depletion (10 Hz stimulation for 10 min) in four children. Muscle biopsies (n = 7) showed mild to severe variation in fiber size. Our experience suggests that many children with congenital myasthenic syndromes might be undiagnosed because of atypical presentation and because additional electrophysiologic studies are required.     

Syndrome of amyotrophic lateral sclerosis after thymectomy performed for myasthenic syndrome

A case of amyotrophic lateral sclerosis was observed developing three months after thymectomy in a woman aged 52 years. The patient had been referred for thymectomy because of myasthenic signs increasing in intensity since 2 years. Myasthenia was confirmed by electrophysiological investigations, and the diagnosis was: myasthenic syndrome and suspected thymoma. During nearly 5 years of follow-up the following observations were made: there was a correlation between thymectomy and the development of ALS syndrome, thymosine administration produced clinical improvement, thymosine administration improved the function of thymus-dependent lymphocytes, thymosine withdrawal (due to non-availability) produced exacerbation of symptoms.     

Pregnancy in congenital myasthenic syndrome

Some case reports have suggested possible worsening of the clinical condition of patients with congenital myasthenic syndromes (CMS) during pregnancy. However, this risk has not yet been quantified in a significant number of patients. Using a standardized report form, we reviewed the gynecological and obstetrical medical history of all patients with CMS listed in the French Registry. The data were reviewed with the assistance of the patients to insure accuracy. We report on 17 pregnancies in eight patients with CMS with mutations in CHRNA1, CHRNE, CHRND, GFPT1, COLQ, or DOK7. Symptoms worsened for six patients during at least one of their pregnancies, and one patient required hospitalization in an intensive care unit during the post-partum period. One patient never recovered to the level of her pre-pregnancy clinical condition. Only one caesarean section was performed. The outcome for children was excellent, with the exceptions of a pulmonary artery atresia in the offspring of a mother on pyridostigmin and a newborn with a severe neonatal congenital myasthenic syndrome (an autosomic dominant slow channel transmission). Our study argues in favor of frequent clinical worsening of symptoms during pregnancy in patients with CMS. These patients should be closely followed by neurologists during the course of pregnancy. However, the overall clinical prognosis is good since the vast majority of patients recovered their pre-pregnancy clinical status six months after the delivery.     

Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome

BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS. SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS. RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024). CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.     

Lambert-Eaton myasthenic syndrome in children

Lambert-Eaton myasthenic syndrome is a presynaptic disorder of neuromuscular transmission. It is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction. It is most often associated with small cell carcinomas of the lung. Rare cases have been reported in children. We recently encountered two children with Lambert-Eaton myasthenic syndrome associated with antibodies to P/Q-type calcium channel but without evidence of neoplasms. Both patients showed prolonged and significant improvement following cyclosporin treatment. The diagnosis of Lambert-Eaton myasthenic syndrome should be considered in children with progressive weakness and a negative work-up for the usual causes. High-frequency repetitive nerve stimulation and P/Q-type calcium-channel antibodies may confirm the diagnosis.     

Congenital Lambert-Eaton myasthenic syndrome.

A 4 year old girl had been hypotonic and areflexic since birth with delayed milestones in motor development. Repetitive stimulation at high rates performed at 3 years elicited an incremental response typical of the Lambert-Eaton Syndrome.     

Myasthenia gravis and myasthenic syndrome

Neurological Sciences - Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune ion channel disorders mediated by antibodies to postsynaptic acetylcholine receptors and...