Leigh-Syndrom

Leigh syndrome, also known as subacute necrotizing encephalomyelopathy (SNEM), is a mitochondrial disorder with progressive neurodegeneration that invariably leads to death, usually in childhood.

Epidemiology

Leigh syndrome is encountered in approximately 1 in 40,000 births, although some populations have much higher incidence (e.g. in Quebec, Canada) . There is no known gender or racial predilection .

Clinical presentation

Typically, symptoms become evident before the age of 2, with the presentation in later childhood (juvenile form) or adulthood (adult form) being uncommon. Symptoms include :

Pathology

Leigh disease is one of many mitochondrial disorders, due to a broad range of genetic mutations in both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) .

Nuclear DNA mutations are more common (~75%) and are inherited in a Mendelian fashion with both autosomal recessive and X-linked inheritance encountered .

Cases due to mitochondrial DNA are less common (25%) and only inherited from the mother .

Some mutations (e.g. SURF1) are particularly devastating .

Chronic energy deprivation leads to histological features such as :

These findings are similar to those seen in infarction .

Genetics

The inheritance pattern may be either autosomal recessive or X-linked.

Markers

CSF lactate may be elevated.

Radiographic features

CT

CT demonstrates regions of low-density matching areas of the abnormal T2 signal on MRI (see below) . Occasionally some of these areas can show contrast enhancement .

MRI

MRI abnormalities are heterogeneous and differ depending on the underlying genetic abnormality . Generally, the distribution tends to be symmetrical.

  • T1: usually demonstrates reduced signal in T2 abnormal areas, although some areas of hyperintensity can be seen, as can some enhancement
  • DWI: in the acute setting some restricted diffusion may be evident
  • MR spectroscopy
    • elevated choline
    • occasionally elevated lactate
    • reduced NAA

Treatment and prognosis

Prognosis is poor, with death usually occurring in childhood. The later the onset, the slower the deterioration. Death is most frequently due to respiratory failure .

The factors associated with a worse outcome are :

  • disease onset before 6 months of age
  • admission to an intensive care
  • brainstem lesions
  • MRS lactate peak

History and etymology

It is named after Archibald Denis Leigh, British neuropathologist, who first described the condition in 1951 .

Differential diagnosis