1. Background

• one of the 5 major conditions that account for the majority of cases of "Progressive Myoclonus Epilepsies"

2. Genetic Defect

• genetic defect -> accumulation of lipopigments in lysosomes in cells of the CNS, liver, muscle, blood vessels, skin, eyes, and lymphocytes
  • CNS - atrophy of both grey and white matter with accumulation in both neural and nonneural elements
  • eye - deposition of lipopigments in rods and cones leads to visual disturbance and abnormal electroretinogram
• may be a metabolic disorder involving the intracellular processing and turnover of lysosomes and their membranes as lipopigments accumulate in lysosomes and dolichol levels are elevated (an important constituent of lysosomal membranes)
• four clinical variants:
  • Type I - Infantile NCL (Haltia-Santavuori Disease)
  • Type II - Late Infantle NCL (Jansky-Bielschowsky Disease)
  • Type III - Juvenile NCL (Spielmeyer-Vogt Disease)
  • Type IV - Adult NCL (Kuf's Disease)

1. Type I (Infantile NCL)

• onset: 9-19 months of age
• death between 5-10 years of age

  1. CNS Manifestations

  1. Initial

  • myoclonic seizures
  • visual loss
  2. Later

  • deterioration of motor abilities and intelligence - (65% never walk)
  • progressive dementia -> vegetative state
  • cerebellar ataxia, hyperkinesia
  • microcephaly, hypotonia
  • optic atrophy -> blind by 2-3 years of age

2. Type II (Late Infantile NCL)

• most common type of NCL
• onset: 2-4 years
• death between 8-12 years of age

  1. CNS Manifestations

  1. Initial

  1. Seizures

  • myoclonic seizures and drop attacks
  • generalized tonic-clonic seizures
  • atonic attacks
  • atypical absences
  • after a few months, myoclonic seizures become prominent
  2. Later

  • deterioration of motor abilities and intelligence
  • nonambulatory by 3-5 years of age
  • progressive dementia -> vegetative state
  • cerebellar ataxia and poor motor coordination
  • microcephaly, spasticity
  • optic atrophy -> blind by 6 years of age

3. Type III (Juvenile NCL)

• onset: 5-10 years
• death 8 years after onset of symptoms

  1. CNS Manifestations

  1. Initial

  • loss of central vision over just a few months
  • intellectual deterioration with decline in school performance
  2. Later

  • deterioration of motor abilities
  • nonambulatory by 13-18 years of age
  • cerebellar ataxia may be mild and present late
  • occasional myoclonic seizures (difficult to control)
  • stuttering dysarthria
  • marked rigidity may present late
  • optic atrophy -> blindness
• cardiomyopathy may develop with thickened ventricle walls and conduction anomalies

4. Type IV (Adult NCL)

• onset: 10-20 years

  1. CNS Manifestations

  • neuropsychologic or personality changes
  • extrapyramidal signs, cerebellar ataxia, spasticity, chorea/choreoathetosis, myoclonus, dysarthria
  • optic atrophy -> blindness less common

1. Diagnostic

2. Electrodiagnostic

3. Imaging Studies

4. Pathology

• accumulation of a specific storage material establishes the diagnosis
  1. Lipopigments

  • consist of ceroid and lipofuscin
  • PAS and Sudan black positive
  • autofluorescent
  • cells contain granular osmiophilic membrane-bound cytoplasmic inclusions or vacuoles
  • in skin these inclusions may form curvilinear profiles or fingerprint profiles

1. Supportive

• no treatment available for underlying disease
• multidisciplinary approach to ongoing problems
  • Paediatrics, Neurology, Orthopedics, PT, OT
  • genetic counselling
• treat myoclonic seizures
  • valproic acid +/- clonazepam