Learning Objectives
- ALS is a diagnosis of exclusion, requiring careful testing for alternate causes
- The course of ALS varies significantly between patients
- ALS is treated by a combination of medication and supportive care
History
TL is a 54 year old supply manager who sees you at the office with a concern of weakness. The symptoms started about 4-5 weeks ago. He tends to walk a 3 mile route 3-4 times per week near his home, and he felt his left foot was not stepping normally, occasionally dragging on the pavement. It seemed hard to lift up the left foot at times, such as when he was lying down. He denied numbness, falling, tremor, or pain. He has not had any change in his weight, trouble swallowing, or trouble breathing. He has not had a feeling of worm like crawling (fasciculation) in his muscles.
He has a history of allergy to cimetidine. He uses triamcinolone cream at times. He has a past medical history of eczema and a tonsillectomy.
TL does not smoke of drink. He is married. He has not had any occupational exposures. He has been working with product distribution for electronics and appliance stores.
His family history is remarkable for heart disease in his brother at age 60. He father passed away of cardiac arrest at age 69. His mother is a healthy 83 year old.
TL denies recently having chest pain or pressure, palpitations, coughing or trouble breathing. He has not had fevers or a sore throat. His thermoregulation has felt normal. He has had a rash on his hands, but that is not abnormal for him. He has not had joint pains, swelling, bruising, or bleeding. He sleeps well. His mood has been well. He denies urinary retention, constipation or incontinence.
Examination
Blood pressure is 122/74. Pulse is 67. Temperature is 98.5 F. TL appears healthy and fit. His carotid auscultation is normal. Heart sounds are normal, regular, and there are no murmurs. Funduscopic and pupillary exams are normal. Fund of knowledge, orientation, language and attention are normal. Facial expression is normal. Eye movements are normal. Hearing and facial sensation are normal. The palate rises normally. Trapezius strength is normal. The voice sounds normal. The tongue has fasciculations on both sides. Strength in the arms is normal. The left leg has reduced strength (level 4) in the hip flexor and ankle dorsiflexor. Otherwise leg strength is normal. Muscle tone is normal. The size of the left tibialis anterior muscle appears reduced. There are fasciculations in the quadriceps on both sides. The deep tendon reflexes in the biceps are increased on both sides. The triceps are normal. The quadriceps reflexes are increased on both sides. The left ankle reflex has sustained clonus. The right ankle reflex is mildly increased. The toes are upgoing to plantar stimulation on both sides. Sensation to pin and proprioception is normal. Finger nose finger movements are normal. He has a mild left foot drop when he walks.
Localization and Neuroanatomy
TL is ordinarily a healthy fellow who has felt a weakness in the left leg of a painless variety. There are no sensory deficits. He also has fasciculations and hyperreflexia. Although weakness can be caused by many illnesses, such as peroneal neuropathy and radiculopathy, the likely cause of his symptom is amyotrophic lateral sclerosis (ALS) because he has a painless, progressive weakness and a combination of upper and lower motor neuron signs in multiple regions of his body.
There are few illnesses that show a combination of upper and lower motor neuron signs. In review, upper motor neuron signs are increased muscle tone, upgoing toes and hyperreflexia, lower motor neuron signs include fasciculations, atrophy and hyporeflexia. Either can be associated with weakness. This patient has atrophy, fasciculations, increased reflexes, and upgoing toes.
In ALS, patients may have substantial changes in their body weight. Painless weakness combined with unexplained weight loss is very suspicious for this condition. The weight loss may be significant- as many as 40-50 pounds at times. The weight loss correlates with loss of muscle bulk throughout the body, but sometimes the strength level does not change much, relative to a bedside examination. People who are known to have a higher muscle bulk, like athletes, may notice a more significant weight loss than sedentary people. Trouble swallowing or reduced appetite may also be associated with weight loss in this condition.
Diagnosis
The diagnosis of ALS is not straightforward. It is important to exclude other illnesses that may mimic the signs of this disorder. Blood testing for illnesses such as leukemia and lymphoma, Lyme disease, HIV, and vitamin storage disorders can be helpful. An MRI of the brain and spinal cord can assess for injuries to these structures that cause similar symptoms. A formal differential diagnosis to consider in the case of painless weakness includes:
- Neoplastic disorder (blood borne, primary CNS)
- Infection (Lyme disease)
- Low serum vitamin B12
- Inflammatory disease (such as multiple sclerosis)
- Radiculopathy or peripheral nerve entrapment
- Muscle or neuromuscular disease (myopathy, myasthenia gravis)
When these illnesses are not consistent with the history, exam, and testing results, the diagnosis of ALS may be supported further by EMG findings. These generally show normal nerve conduction velocities and evidence of denervation within the muscle fibers of three spinal segments. (There are four spinal segments- cranial, cervical, thoracic, and lumbar.)
Treatment
ALS is a treatable illness, but treatment typically does not prevent progression, and death tends to be the outcome of the illness. The symptoms may be present for months or years. The cause of death is often due to difficulty breathing or swallowing, and significant disability affecting walking, using the arms, or speech may be part of the illness.
The treatment of ALS is partly supportive care and partly pharmacological management. The medication riluzole is helpful is delaying progression of the illness. It is used twice daily as a 50 milligram tablet. Possible side effects include worsening of liver function, especially in patients with liver illnesses. Patients with ALS may also benefit from assistance with speech therapy devices, a power wheelchair or walker, tube feeding, noninvasive ventilation or mechanical ventilation.
When treating a patient with ALS, it is important to plan for the possible need for medical assistance, and determine a patient’s wishes for intervention. Some patients prefer not to use artificial life sustaining measures, and others do. Some patients may have a long life with the help of these interventions. The diagnosis of ALS may be made years before the symptoms become life-threatening. Patients requiring nutritional or ventilator support may wish to consider their emergency resuscitation orders (DNR orders).
ALS is a variable illness that affects different people is different ways. Some patients will primarily show symptoms affecting muscles of the face (bulbar symptoms), the legs or the arms (bipedal or bibrachial symptoms). Other patients will have a generalized condition that affects all parts of their body. Some patients will show a rapid loss of function, other patients will have slow, smoldering illness that lasts for years. The course of ALS is not the same for every patient.
An illness similar to ALS is primary lateral sclerosis (PLS). This illness is like ALS in that there are upper and lower motor neuron features, and the test results may be similar. Unlike ALS, PLS is very slowly progressive, and although it may affect motor function, it rarely results in death. Riluzole medication is not approved for use in this condition. Patients with PLS rarely have symptoms affecting breathing or swallowing.
Review Questions
- The diagnosis of ALS may be clinched by the appropriate history and:
a. a physical examination typical of ALS
b. a set of normal brain MRI and cervical spine MRI results
c. EMG study showing denervation in multiple spinal segments
d. laboratory tests for CPK, Lyme disease, vitamin B12, etc.
e. ALS is a diagnosis of exclusion, no single test may be used to clinch the diagnosis - The clinical course of ALS is typically:
a. progressive painless weakness, affecting the face, arms, trunk and legs
b. weakness and numbness, affecting the body
c. progressive weakness and weight loss
d. there is no true typical course of ALS
e. progressive difficulty swallowing and breathing - Treatment of ALS is best done with
a. The medication riluzole
b. The medication natalizumab
c. supportive care for walking, swallowing, talking, etc.
d. answers A and C
e. All of the above