Familial Childhood Primary Lateral Sclerosis with Associated Gaze Paresis

Abstract

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).

Infantile ascending hereditary spastic paralysis (IAHSP)

“…34 Motor-evoked responses in PLS are absent or very delayed, and sensory-evoked potentials are normal or mildly delayed. 37 We found the same features of conjugate saccadic gaze paresis in some families but not in all our patients. [36][37][38] The sporadic case, whose symptoms started at age 12 months, had a faster disease progression than our patients, with a 38-month course and death at 47 months.…”

“…This disorder occurs sporadically in adults, and pathologic findings showed the absence of Betz's cells from layer 5 and a decreased number of pyramidal tract neurons in layers 3 and 5 of the pericentral gyri, with preservation of the anterior horn cells. [36][37][38] The sporadic case, whose symptoms started at age 12 months, had a faster disease progression than our patients, with a 38-month course and death at 47 months. In a single patient, MRI showed an increased intensity signal at the site of the pyramidal tract on T2weighted images, extending from the corona radiata through the posterior arm of the internal capsule to the pons.…”

“…[36][37][38] The sporadic case, whose symptoms started at age 12 months, had a faster disease progression than our patients, with a 38-month course and death at 47 months. The recent findings of ALS2/Alsin mutations in the previously described families 37,38 established that this condition was allelic to ALS2. The first family, from Kuwait, included three affected siblings whose clinical presentation was similar to our patients', although a short follow-up was described.…”

Neuropsychological changes in patients with primary lateral sclerosis

“…The relationship between PLS and other neurodegenerative diseases has been a subject of debate ever since the description in PLS of neuropsychological impairment (10,13), ocular movement abnormalities (14,15), cortical atrophy (9,10,16) and intellectual impairment (10). Behavioural changes with bilateral atrophy of the frontal and temporal lobes have been reported in association with PLS in one patient (16).…”

Primary lateral sclerosis, hereditary spastic paraplegia, and mutations in thealsingene: Historical background for the first International Conference

“…All could be familial or sporadic. Five years later, Gascon, Siddique (95) and their associates described ''familial childhood PLS with gaze paresis'', beginning in late infancy.…”