It is a rare disease affecting the neuromuscular junction is, more frequently an autoimmune disease. This is most frequently seen in small cell lung cancer (SCLC). The characteristic clinical presentation is muscle weakness. It is about those antibodies to voltage-gated calcium channels (VGCCs) on the presynaptic nerve terminals leads to decrease in release of acetylcholine (ACh).  

Lambert-Eaton myasthenic syndrome (LEMS) is another rare disorder of the voluntary muscles and is at least 46 times less frequent than myasthenia Gravis. Nevertheless, it is important to underline that the annual incidence of LEMS is only 10 to 14 times less than that in MG and LEMS patients show more unfavorable prognosis and survival rates especially in case with SCLC-associated LEMS. 

LEMS affects the male persons predominantly with 60% to 75 % of the cases found to be in males while MG is more frequent in women. Paraneoplastic LEMS often occurs at the age of 58 on average. However, patients with LEMS with no association to cancer should have an age and gender distribution like MG and has an onset at 35 years and peaks again at 60. If LEMS is not associated with malignancy, then the prognosis of the disease is relatively good, and the mortality rate is nearly normal. 

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular disorder that results from autoantibodies that target voltage-gated calcium channels (VGCC) on the presynaptic nerve terminals and thus reduced acetylcholine (ACh) release and muscle weakness. This disruption mainly occurs with antibodies directed against the P/Q subtypes of VGCC which are present in approximately 85% of all LEMS cases. Paraneoplastic LEMS, mostly associated with SCLC involves tumor cells expressing VGCCs which later induce autoantibodies. Non-tumor LEMS have genetic factors HLA-B8 and HLA-DR3 like other autoimmune diseases such as myasthenia gravis. In addition to muscle weakness, LEMS may be associated with constipation and abnormal pupils. 

LEMS can be classified into two types: paraneoplastic, and non-paraneoplastic, referred to as Non-Tumor LEMS (NT-LEMS). NT-LEMS is not associated with malignancies on the other hand, 60% to 70% of LEMS patients have an associated tumor, particularly the paraneoplastic type associated with SCLC. 

LEMS can also be associated with other types of cancers which include non-SCLC, mixed lung carcinoma, prostate cancer, thymoma and lymphoproliferative disorders. However, LEMS can be diagnosed up to 5 to 6 years before the onset of SCLC is experienced. Smoking history is one of the major precursors to developing LEMS. Also, about 65% of the young patients with NT-LEMS have a genetic link to the HLA–B8–DR3 haplotype. 

Patients with Lambert-Eaton myasthenic syndrome (LEMS) report reduced quality of life due to their general symptoms and potential side effects of treatments for the disease. On the other hand, most patients have satisfactory responses to symptomatic and immunosuppressive therapies, 60% of the patients are independent in their daily activities at the time of diagnosis, 85% of them are independent within one year of treatment. 

Recent literature shows that, depending on the nature of LEMS – paraneoplastic or non-paraneoplastic – patients’ life expectancy might decrease. About patient survival, based on the study on NT-LEMS, it was discovered that its lifespan is as high as that of the normal population. In the case of paraneoplastic LEMS, the survival can be predicted according to the tumor type, being predominantly SCLC. Notably, the LEMS-SCLC patient group has a favorable survival as compared to the pure SCLC group, with median survival of 17 months compared to the 7 months. 

Age Group 

LEMS can affect young adults as well as senior citizens, though the age of onset appears to be somewhat earlier in the paraneoplastic instances. 

Paraneoplastic LEMS: Can present at any time, but most common in patients around the age of 60 years and is strongly associated with SCLC. 

Non-Paraneoplastic LEMS (NT-LEMS): May start at an early age though the most prominent onset is at age 35 years and another group at around 60 years of age. 

The physical examination in LEMS also mostly shows proximal muscle weakness, diminished or absent DTR with post-exercise facilitation and obvious features of autonomic dysfunction. The fact that muscle strength and reflexes become temporarily enhanced with repeated use is one of the diagnostic indicators. 

Paraneoplastic LEMS: Close association with underlying malignancies, specially small cel lung carcinoma. Non-SCLC, prostate cancers, thymoma, lymphoproliferative conditions are other cancer types associated with the disease. 

Non-Paraneoplastic LEMS: Based on Myasthenia gravis (MG,) and has a familial tendency related to HLA-B8, HLA-DR3, and DQ2 HLA complexes. 

Paraneoplastic LEMS: Usually comes with subacute-chronic onset and the predominant clinical feature of the initial symptomatology is weakness, more especially proximal muscle weakness. Some of the features may include dry mouth, constipation, and orthostatic hypotension because of the autonomic dysfunction. 

Non-Paraneoplastic LEMS: Symptoms may be more subtle, with gradual progression of muscle weakness and involvement of the autonomic nervous system. This may be slightly lower than in paraneoplastic LEMS, particularly in young individuals it can be less marked. 

Symptomatic Management: 

• Acetylcholinesterase Inhibitors: Some drugs like pyridostigmine which boosts the neuromuscular junction transmission may be employed; however, they are not as potent as in LEMS compared to in myasthenia gravis. 
• Exercise Therapy: Physical therapy is useful in preventing and treating muscle loss especially in the case of weakened muscles and /or reduction in mobility. 

Immunosuppressive Therapy: 

• Corticosteroids: Corticosteroids such as prednisone are useful in steering down autoimmune action and enhancing symptoms. They are commonly applied to be initial interventions in treatment processes. 
• Other Immunosuppressants: For the long-term care of cirrhotic patients, other immunosuppressants such as azathioprine, mycophenolate mofetil, and methotrexate may be used if corticosteroids are not fully effective or pose significant risks. 

Plasma Exchange and Intravenous Immunoglobulin (IVIG): 

• Plasma Exchange: Beneficial in quickly and effectively lowering antibody titre and ameliorating the clinical manifestations particularly the severe cases or during flare-ups. 
• IVIG: May be useful in attenuation of the actions of pathogenic antibodies and enhancement of the neuromuscular junction transmission in some patients. 
• Cancer Management: As for paraneoplastic LEMS linked to SCLC or other cancers, managing cancer remains a part of first-line treatment. This may be in form of surgery or through the use of chemicals such as in chemotherapy or through rays such as in radiation therapy. 
• Supportive Care: Other specific areas like the management of Autonomic dysfunction for instance medication for Orthostatic hypotension. 
• Nutritional Support: Handling challenges on how to manage feeding and adequacy of diet in patients with OHS. 
• Emerging Therapies: Currently, there are further developments in the treatment effect research for new drug therapies like monoclonal antibody-targeting immune pathways. 

Neurology

Physical Therapy: Activities that help to build muscle strength, increase range of motion, and reduce the degree of fatigue. 

Lifestyle Modifications: Energy saving methods, and strategies, and adjusting of the range of activity. 

Nutritional Support: Feeding and fluid intake to support the functional limitations due to dysphagia as well as other medical problems. 

Education and Self-Management: Psychoeducation and coping skills for enhancing the patients’ knowledge and enhancing their abilities to manage their lives. 

Supportive Care: Psychological help, steroids, physiotherapy, and help with search of work and work-related services to lead an independent life. 

Neurology

Amifampridine (Firdapse, Ruzurgi): It modulates intracellular calcium concentration in nerve endings by blocking potassium channels of voltage-dependent type. Such an increase in calcium levels helps in the causing release of the vesicles that contain acetylcholine, hence enhancing neuromuscular transmission. It is recommended for the management of Lambert-Eaton myasthenic syndrome (LEMS) in adult and paediatric patients, 6 years of age and older. 

Neurology

Pyridostigmine Bromide (Mestinon, Regonol): Pyridostigmine is an anticholinesterase that competes with acetylcholine (ACh) for binding at cholinesterase sites, thus blocking the enzyme’s ability to break down ACh at synapses. This leads to high accumulation of ACh and improved stimulation of cholinergic receptors on the NMJ. It has recently been demonstrated that monotherapy with cholinesterase inhibitors is ineffective but using them with 3,4-diaminopyridine drugs may have some efficacy. 

Guanidine: The mechanism of action of guanidine includes an increase in the intracellular levels of calcium through potassium channels blockade and inhibition of mitochondrial respiratory chain. This helps to spread out the nerve terminal action potential and thus further amount of ACh releasing occurs after impulses in the neuron. It also decreases the frequency of depolarisation or repolarisation of the membrane of muscle fibres and in many LEMS patients alleviates temporarily muscle weakness and fatigue. The maximal effect may require 2 to 3 days to become observable and it is used in adults to treat muscle weakness and fatigue that occurs with LEMS. 

Neurology

Prednisone: Thus, prednisone works as an immunosuppressant for managing the autoimmune disorders. It is used frequently in conjunction with azathioprine more than as a stand-alone medicine. 

Azathioprine: Like other immunosuppressive drugs, azathioprine inhibits cell division and prevents the rate of metabolism as it has an impact on purine metabolism and makes DNA, RNA and proteins synthesis to get blocked. They may slow down the creation of immunologic cells and temper the actions of the body’s safeguard substance. 

Neurology

Intravenous Immunoglobulin (IVIg): It is postulated that IVIg positively affects several aspects: the presence of anti-idiotypic antibodies that counteract the pathogenic effects of autoantibodies and their ability to bind Fc receptors on macrophages; a decrease in pro-inflammatory cytokines such as interferon gamma; reduced T and B cell activation, while increased suppressor T cells. 

Neurology

Plasmapheresis (Plasma Exchange): It is a procedure that is used to filter out antibodies from the blood stream. It may have useful effects in easing symptoms by decreasing the number of autoantibodies that affect neuromuscular junction. 

Intravenous Immunoglobulin (IVIG): It is given for the immune system regulation and decrease in autoantibody levels, for symptomatic control. 

Immunosuppressive Therapy: Although not a specific procedure, immunologic modification including the use of corticosteroids or other immunosuppressive agents such as azathioprine or mycophenolate mofetil may be a part of the overall therapeutic management. 

Neurology

The management of LEMS generally goes through certain stages. In the acute phase, therapeutic approach is entirely supportive and includes use of acetylcholinesterase inhibitors and 3,4-diaminopyridine in combination with immunomodulatory treatments like plasmapheresis or intravenous immunoglobulin (IVIG). The maintenance phase involves sustained immunosuppressive treatment, with medications like corticosteroids or azathioprine when needed, and integrating any related malignancies like small-cell lung cancer. Follow up includes constant observation to fine tune therapies and control symptoms in such manner that the life of the patient would be optimised.