Familial Amyotrophic Lateral Sclerosis

This 58 year old woman was referred to Dr. Robert Brown in March 1995 for evaluation of slurred speech. She remained under his care until her death. On examination she had signs of a pseudobulbar palsy: Dysarthria and dysphagia Diminished palatal movement with positive gag bilaterally Diminished rapid movements of the tongue A 1+ jaw jerk Muscle tone throughout was minimally increased and the deep tendon reflexes were hyperreflexic bilaterally. Electromyographic studies scanning multiple muscles for fasciculations were negative. Seven months later in September 1995, her speech was unintelligible and her palate hardly moved at all. She had strong eye closure but mouth opening was weak and she had bifacial weakness. Her reflexes remained brisk throughout. Urine studies for heavy metals, arsenic, cadmium, lead and mercury were negative. Repeat electromyographic studies now showed a picture of widespread denervation that helped confirm the diagnosis of amyotrophic lateral sclerosis (ALS) with a progressive bulbar onset. In November 1995, she could hardly speak and she was no longer able to protrude her tongue or whistle. As her disease progressed, she became aware of difficulty walking and in April 1996 she returned for evaluation having fallen on two occasions. By this time she had lost the ability to speak and was mute. She had difficulty chewing and swallowing, particularly liquids, and noted some difficulty as well with closing her eyes and focusing. On examination, she was mute, smiling and laughing readily with some emotional lability. She had slowing of her eye movements and impaired eyelid closure but she closed her eyes when sleeping. She was unable to smile fully on a volitional basis although when she was amused she had a full smile. The tongue could only be protruded approximately 0.5 cm. beyond the teeth with absent lateral movements. There was no atrophy of the tongue or fasciculation. In September 1996 she had a G-tube placed. Progressive weakness of the legs led to her becoming completely paralyzed from the waist down and she was confined to a wheelchair by September 1997. There was no evidence of respiratory distress. A neurovisual exam at that time, eighteen months after the onset of ALS, documented •A supranuclear paralysis of saccadic upgaze greater than downgaze with intact vertical pursuit •Slow horizontal gaze to right and left with the patient needing to move her head and eyes to look to either side •Saccadic horizontal pursuit •Convergence insufficiency with an exophoria on alternate cover test fixating on a near target •Slow volitional eye closure with preserved spontaneous eyelid opening and reflex blinking to threat and a loud noise. •No square wave jerks or nystagmus. Family history is significant for a mother who died of ALS at age 60 after a two year illness. Her mother had one sister who died without neurologic disease at age 80. The patient has two siblings who are without neurologic disease. She herself has 3 children, the oldest is age 37. The patient's DNA was tested for a mutation of the superoxide dismutase (SOD1) gene and was negative. The Vinculum Associated Binding Protein (VABP) gene had not been discovered at this time. The patient's ALS continued to progress, with predominantly upper motor neuron bulbar signs and spasticity of the limbs. She died in 1998. No autopsy was performed. See also: http://content.lib.utah.edu/cdm/ref/collection/ehsl-shw/id/238