Familial childhood primary lateral sclerosis with associated gaze paresis.

Three children from consanguineous parents began losing the ability to walk in late infancy. Despite chronically progressive weakness leading to wheelchair dependence by adolescence and later loss of motor speech production, intellect remained preserved. Examination revealed upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia, without dementia, cerebellar, extrapyramidal or sensory signs. In addition they exhibited a diffuse conjugate saccadic gaze paresis, especially severe on down-gaze. CT and MRI scans of brain and spinal cord, EEGs, visual and brainstem auditory evoked potentials, CSF examinations, enzyme assays for lysosomal storage diseases, blood amino acids and urine organic acids were all normal. Cortical somatosensory evoked potentials were poorly configured in two of the patients, though they had normal central conduction. EMG showed no signs of denervation. Nerve conduction studies showed normal peripheral motor and sensory conduction velocities. Transcranial magnetic stimulation of the brain elicited no motor-evoked potentials. Despite the lack of neuropathological confirmation, the clinical course and neurophysiologic data strongly support the diagnosis of a familial (autosomal recessive) primary lateral sclerosis (PLS).