Annals of Indian Academy of Neurology
: 2007  |  Volume : 10  |  Issue : 1  |  Page : 55--57

Adult onset Leigh syndrome

Lekha Pandit1, Gayatri Narayanappa2, Lathika Shetty3, Sree Krishna3,  
1 Department of Neurology, KS Hegde Medical Academy, Mangalore, Karnataka, India
2 Department of Neuropathology, National Institute of Mental Health and Neurological Sciences, Bangalore, Karnataka, India
3 Department of Radiology, KS Hegde Medical Academy, Mangalore, Karnataka, India

Correspondence Address:
Lekha Pandit
Department of Neurology, KS Hegde Medical Academy, Deralakatte, Mangalore - 575 108, Karnataka


Leigh syndrome is a rare progressive mitochondrial disorder of oxidative metabolism. Though it has been reported in infancy and childhood, it is rarely described in adults. The authors describe a patient who had clinical and magnetic resonance imaging features diagnostic of Leigh syndrome, with supportive biochemical and muscle histochemistry evidence.

How to cite this article:
Pandit L, Narayanappa G, Shetty L, Krishna S. Adult onset Leigh syndrome.Ann Indian Acad Neurol 2007;10:55-57

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Pandit L, Narayanappa G, Shetty L, Krishna S. Adult onset Leigh syndrome. Ann Indian Acad Neurol [serial online] 2007 [cited 2020 Aug 9 ];10:55-57
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Full Text


Leigh syndrome (LS) is a mitochondrial disorder of heterogeneous origin. Mutations in a number of mitochondrial and nuclear encoded genes involved in energy metabolism can result in this progressive disorder. These include mitochondrial respiratory chain complexes I, II, III, IV and V, which are involved in oxidative phosphorylation and the generation of ATP and components of the pyruvate dehydrogenase complex. Clinical symptoms depend on sites of neuro-pathological involvement. Lesions are characteristically bilateral and can involve more than one area in the brain including brainstem, thalamus, basal ganglia, cerebellum and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis or capillary proliferation.[1]

 Case Report

A 26-year-old male, a teetotaler, presented with gradually increasing headache of three weeks duration in the background of which he developed drooping of both eyelids. In the past he has noticed diminished hearing particularly in the left ear. He had recurrent episodes of throbbing headaches in the previous two years that was treated as migraine. There was no history of fever or other preceding illnesses. He was an only child born of non consanginous parentage with no family history of neurological ailments. On examination he was conscious and oriented. General physical examination was unremarkable. He had bilateral ptosis, ocular mobility was restricted in upward plane but pupils were normal and reacting. Fundus examination was normal. He had evidence of bilateral moderate nerve deafness. Over the next one week he had severe headache and became drowsy. He also developed brisk deep tendon reflexes with bilaterally extensor plantar reflexes.

The patient was initially investigated as follows. His routine counts were normal. Serum electrolytes, renal and liver functions were normal. Electrophysiological evaluation including nerve conduction studies and repetitive nerve stimulation tests were negative. Neostigmine test was negative. After his sensorium deteriorated, an MRI was done which showed [Figure 1] symmetric hyperintensities in the basal ganglia extending into the peri third ventricular thalamus and the periaqueductal regions of the mid brain. EEG showed generalized slowing without epileptiform activity. Fasting serum lactate level was 6.8 mmol/ L (normal -0.8- 2.4 mmol/L). Fasting cerebrospinal fluid (CSF) lactic acid level was 4.1 mmol/L (normal 1.1 -2.3 mmol/L). The CSF cytochemistry was normal. Further metabolic studies revealed normal serum copper, ceruloplasmin and urine copper levels. Test for hypercoagulable states were normal. A right quadriceps muscle biopsy was done. Histochemistry revealed [Figure 2] A and B sub sarcolemmal accumulation of mitochondria in muscle biopsy and occasional cytochrome oxidase (COX) negative fibres. Muscle DNA was extracted by standard procedure and sent for mitchondrial mutational studies (Mitochondrial Diagnostic Services, Department of Neurology, University of Newcastle upon Tyne, United Kingdom.) Automated sequencing of the ATPase 6 and 8 genes of mitochondrial DNA were done to screen for known and novel mutations. No pathogenic mutations were detected. Additional studies were done to exclude mutations associated with mitochondrial encephalopathy and lactic acidosis (MELA) and myoclonic epilepsy and ragged red fibers (MERRF), which were negative.

He was given intravenous thiamine infusion initially as 300 mgms /day for the first week, 100 mgms daily for the second week and was followed by oral substitution subsequently. Within three days of receiving thiamine he became alert with gradual improvement in ptosis. By the end of the fortnight, he was free of headache and ptosis had completely recovered. Vertical gaze paresis improved over the next one month. He remains asymptomatic on follow-up 18 months after his illness.


When confronted with an MRI pattern of bilateral basal ganglia hyper intense lesions, the differential diagnosis includes hypoxic injury, mitochondrial diseases, toxin exposure (e.g., carbon monoxide, methanol), osmotic myelinolysis, infections or postinfectious demyelination, Wilson's disease, deep venous thrombosis and thrombotic microangiopathy. These conditions have been carefully eliminated in our case. The diagnostic criteria for LS are as follows:[2] 1) progressive neurologic disease with motor and intellectual developmental delay; 2) signs and symptoms of brain stem and/or basal ganglia dysfunction; 3) elevated lactate levels in the blood and/or CSF; and 4) one or more of the following: a) characteristic features of LS on neuroimaging[3] (symmetrical hyperintense lesions in the basal ganglia and/or brain stem on T2-weighted magnetic resonance images); b) typical neuropathologic changes at postmortem examination; or c) typical neuropathologic findings in a similarly affected sibling. Our patient satisfied the clinical, MRI and biochemical criteria for LS. In addition he also had deafness - another hallmark of mitochondrial disorders. Muscle histochemistry supported the diagnosis. The genetic dysfunction underlying our patients disease could not be ascertained based on the limited mitochondrial genetic studies that were done in our patient. Recent studies have shown that recognized mtDNA mutations only account for a small proportion of cases of mitochondrial disease.[4] In addition, nuclear DNA mutations account for a substantial number of disorders characterized by mitochondrial dysfunction.

In our patient we were unable to perform mitochondrial respiratory chain analysis in muscle or fibroblasts. However the clinical features, raised lactate levels and the un ambiguous muscle histo chemistry confirmed the diagnosis of a mitochondrial cytopathy. The striking MRI abnormalities on the other hand have been previously described only in the LS subtype of mitochondrial disorder[3],[5] which we believe fits our patients presentation best.

Adult onset LS has been rarely reported. Anecdotal reports of improvement have been described with vitamin cocktails, cofactors and oxygen-radical scavengers, with the aim of mitigating, postponing or circumventing the postulated damage to the respiratory chain.[6] Our patient had striking resemblance to the case described by Goldengerg et al .[5] in age, clinical presentation, MRI abnormalities and the remarkable improvement with thiamine infusion. The well documented improvement in COX deficient LS and so also in the benign infantile COX deficient myopathies indicate that some forms of mitochondrial disorders appear to have a better prognosis than previously thought.


The authors acknowledge the help of Prof. D. M. Turnbull, Mitochondrial diagnostic services, Department of Neurology, The Medical School, Framlington Place, University of Newcastle upon Tyne, United Kingdom.


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