Appendix e-1. Detailed case reports
V-3: This 55-year old patient presented with delayed motor milestones in early childhood. Pregnancy and delivery were uneventful. He developed progressive dysarthria during elementary school and his speech became unintelligible by the age of 11 years. He also developed dysphagia and excessive salivation, as well as weakness and spasticity in the legs with slowly progressive difficulty walking. He became wheelchair bound at the age of 50 years. He also presented with complains of dyspnea especially at night and obstructive sleep apnea has been diagnosed.On his most recent examination he had slow and saccadic eye movements. There was spastic quadriparesis with increased muscle tone especially in the legs and pseudobulbar palsy with almost complete loss of mobility of the tongue and oropharyngeal muscles. His reflexes were brisk in the legs and plantar responses were extensor bilaterally. He denied any sensory loss. Extensive laboratory evaluation included normal routine hematological and biochemical blood studies. Chromosomal analysis, plasma amino acids, and lactate levels were also normal. Nerve conduction studies at the age of 47 showed normal velocities and mildly reduced compound muscle action potential amplitudes in the lower extremities. He has been treated symptomatically with baclofen and CPAP at night.
V-4: This42-year old younger sister of patient V3 was born at full term following uneventful pregnancy and delivery but was never able to stand or walk. She has been wheelchair bound all her life and presented with progressive weakness and spasticity in the extremities. In addition she had difficulty swallowing since early childhood and could never speak clearly, although she was able to read and write at elementary school. Gradually she became anarthric. On her most recent examination she had severe pseudobulbar palsy with complete anarthria, severely impaired orolingual movements but no tongue atrophy. Palate movement was very poor but gag reflex was brisk. She had slow, hypometric and saccadic eye movements. There was spastic quadriplegia with hypereflexia and extensor plantar responses bilaterally. She denied sensory loss.Routine hematological and biochemical blood studies were normal. Chromosomal analysis, plasma amino acids, and lactate levels were also normal. Nerve conduction studies of the upper limbs were normal. Visual evoked and somatosensory evoked potentials from the upper and lower extremities were normal. A CT scan of the brain showed no focal abnormalities. She has been treated symptomatically with baclofen.
VI-3: This 16 year old boy born after uneventful pregnancy and delivery presented in early childhood with leg spasticity and dysarthria. He had scissoring gait and toe walking when he first walked at the age of 2 years. He was also noted to have dysarthric speech when he first talked. His mental development was normal. His speech became progressively worse and in the last few years it has become almost unintelligible. Recently he has also been chocking on fluids. He underwent tenotomies in the feet to treat spasticity but his gait has been gradually deteriorating. While in early childhood he could walk fast, recently he was able to only make a few steps with a walker and he started having great difficulty with transfers because of spasticity. His hands became also slow with impairment of dexterity.On his most recent examination his mental status was normal. He had slow and saccadic eye movements, although they were of full range. Facial, lingual and pharyngeal movements were very slow and spastic. He could not protrude the tongue, although no tongue atrophy was noted. He also had severe dysarthria and exaggerated gag reflex. Hearing and vision were intact. On motor examination he had spasticity and loss of dexterity in both hands with mild atrophy of the hand muscles, and almost athetotic positioning of the fingers. In the lower extremities there was severe spasticity, cloniform reflexes throughout, extensor plantar responses bilaterally, and impairment of voluntary movements. Gait was very slow and spastic. There was no cerebellar dysfunction. There was no objective sensory loss.His nerve conduction study showed normal motor and sensory nerve responses. Needle EMG showed no evidence of denervation in selected arm muscles to suggest any lower motor neuron involvement.