Leigh-Syndrom

ähnliche Suchen

Leigh-Syndrom
Leigh disease
Leigh's disease (mitochondrial disorder)
Leigh's disease
Leigh syndrome
subakute nekrotisierende Enzephalomyelopathie
Morbus Leigh
infantile subacute necrotizing encephalopathy
juvenile subacute necrotizing encephalomyelopathy
leighs syndrome
Leigh's syndrome
Sub acute necrotising encephalomyelopathy
Leigh's encephalopathy
Subacute Necrotising Encephalomyelopathy (SNEM)

siehe auch

Korsakow-Syndrom
Demyelinisierende Erkrankung
akute hämorrhagische Leukoenzephalitis
Mitochondropathie

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 :

• psychomotor delay/regression
• superimposed signs of basal ganglia and brainstem dysfunction
  • ataxia
  • ophthalmoplegia
  • dystonia 
  • respiratory rhythm disturbance
  • cranial nerve palsies

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 :

• spongiform degeneration
• capillary proliferation
• demyelination
• neuronal loss
• gliosis

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.

• T2: characterized by high signal typically in : 
  • brainstem
  • periaqueductal grey matter
  • medulla
  • midbrain
  • putamen: characteristic but not always present
  • other sites of T2 signal change include: 
    • the remainder of the corpus striatum [globus pallidus and caudate nucleus (heads)]
    • subthalamic nuclei
    • substantia nigra
    • thalami
    • involvement of cerebral or cerebellar white matter is unusual

• 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

• Wernicke encephalopathy (WE)
  • similar appearance but different demographics
  • mammillary bodies not involved in Leigh disease
  • enhancement more common in WE
  • hemorrhagic change more common in WE
• other mitochondrial disorders
  • brainstem and basal ganglia involvement less pronounced
• acute necrotizing encephalitis of childhood
  • lactate levels are usually normal
• Biotin-thiamine-responsive basal ganglia disease

Siehe auch:

• Korsakow-Syndrom
• Demyelinisierende Erkrankung
• akute hämorrhagische Leukoenzephalitis
• Mitochondropathie

und weiter:

• T2 hyperintense Basalganglien
• dysmyelinating disorders
• Leukodystrophie
• choline:creatine ratio
• Kohlenmonoxidintoxikation
• Chorea Huntington
• Kearns-Sayre-Syndrom
• Pyruvatdehydrogenase
• Mitochondriale Encephalomyopathie mit Lactatacidose und Schlaganfall-ähnlichen Episoden (MELAS)
• mitochondrial encephalopathy with lactic acidosis and stroke-like episodes
• Pyruvat-Dehydrogenase-Mangel
• Neonatale Leukodystrophie
• putaminal necrosis