Abstracts

Rationale: Sandhoff disease (GM2 gangliosidosis) is a very rare neurodegenerative disease caused by deficiency of the enzymes Hexosaminidase A and B. We report the evolution of electroencephalographic (EEG) changes during the life of a patient with confirmed Sandhoff disease. Methods: The patient presented at 12 months of age because of global developmental delay. His initial exam documented macrocephaly, hepatomegaly, axial hypotonia and appendicular hypertonia, hyperreflexia and ankle clonus. Ophthalmological examination confirmed the presence of cherry red spots. Lysosomal enzymes showed extremely low plasma levels of hexosaminidase A (14.6%) and hexosaminidase B (2%), confirming the diagnosis of Sandhoff disease. Results: An initial routine EEG at 13 months was normal. At 16 months, he developed paroxysmal episodes of neck hyperextension. Video EEG documented that these episodes were not seizures. However, the EEG background had become abnormal, with poor organization of the frequency-amplitude gradient, frontal and temporal intermittent rhythmic delta activity, and frequent multifocal spikes. By age 21 months he was very irritable and spastic, and could not swallow. He had intermittent episodes of eye twitching followed by asymmetric bilateral facial twitching lasting up to 3 hours. Routine EEG confirmed the presence of subclinical seizures arising independently from the right temporal and left frontal regions, but clinical seizures were not recorded. The EEG background was slow, disorganized, and asymmetric, with suppression over the left hemisphere. There were generalized and independent right hemispheric subclinical electrodecrements, as well as multifocal sharp waves. He was treated with topiramate, but at a dose of 5mg/kg/day he developed new seizures with rhythmic leg twitching. Treatment was changed to phenobarbital 5mg/kg/day and the clinically-apparent seizures stopped. A swallow study documented aspiration. One month later, at age 22 months, he developed intermittent episodes of prolonged apnea. He was hospitalized and required intubation. EEG monitoring showed a diffusely suppressed and unreactive background. No seizures or sharp waves were recorded. The patient died a few hours later after the family elected to withdraw support. No autopsy was performed. Conclusions: This report is the first to document the natural history of EEG features in a patient with Sandhoff disease. The serial EEGs in our patient documented progressive deterioration of the EEG background, evolving from a normal study at 13 months of age to focal and then generalized slowing and background disorganization, along with multifocal epileptiform discharges, electrodecrements, and focal seizures by age 21-months and then becoming unreactive and diffusely slow prior to his death at age 22-months. The EEG features mirrored the patient s clinical decline, with progressive neuromotor impairment and symptomatic epilepsy syndrome.