Emergency. 2017; 5 (1): e43

CA S E RE P O RT

Head Trauma as a Precipitating Factor for Late-onset
Leigh Syndrome: a Case Report
Farzad Ashrafi1∗, Hossein Pakdaman1, Mehran Arabahmadi1, Behdad Behnam1

1. Brain Mapping Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Received: October 2016; Accepted: October 2016; Published online: 14 January 2017

Abstract: Leigh syndrome is a severe progressive neurodegenerative disorder with different clinical presentationsthat usu-
ally becomes apparent in the first year of life and rarely in late childhood and elderly years. It is causedby failure
of mitochondrial respiratory chain and often results in regression of both mental and motor skills and might
even lead to death. In some of the inherited neurodegenerative diseases like Alexander disease, head trauma is
reported as a trigger for onset of the disease. We present a late onset Leigh syndrome in a 14-year-old girl whose
symptoms were initiating following head trauma.

Keywords: Leigh disease; craniocerebral trauma; precipitating factors

© Copyright (2017) Shahid Beheshti University of Medical Sciences

Cite this article as: Ashrafi F, Pakdaman H, Arabahmadi M, Behnam B. Head Trauma as a Precipitating Factor for Late-onset Leigh Syndrome:

a Case Report. Emergency. 2017; 5 (1): e43.

1. Introduction

Leigh syndrome (LS) is a rare progressive neurodegenerative

disorder, whichusuallymanifests in early childhood. More

than 75 gene mutations, related to pyruvate metabolism and

mitochondrial respiration, have been found responsible for

LS (1). Although LS often occurs in early childhood, there

are few reports of late-onset presentation (2). Basal ganglia,

cerebellum and brain stem are typically involved by necro-

tizing changes. The most common manifestations include

psychomotor involvement, ataxia, dystonia, seizures, nystag-

mus, ophthalmoplegia, and respiratory distress (3, 4). This

syndrome can present with a variety of clinical presentations,

progression and prognosis (5). However, all previous cases

have been reported without any trigger before the onset of

symptoms. In this report, we present a 14-year-old girl who

initially developed seizure and ataxia following head trauma,

and finally the diagnosis was proved based on manifesta-

tions, characteristic imaging findings and dramatic response

to mitochondrial cocktail.

∗Corresponding Author: Farzad Ashrafi; Department of Neurology,
Shohadaye Tajrish Hospital, Vali-asr Street, Tajrish square, Tehran, Iran.
Tel:+982122718003; Mobile:+989121937930; Email: farzad.ashrafi@gmail.com

2. Case presentation:

The patient was a 14-year-old girl of consanguineous par-

ents admitted to our emergency department with complaint

of respiratory distress. She had no family history of neu-

rological disorders and had just one 18-year-old sister who

was in excellent health. She had no significant past med-

ical history except mild bilateral hearing loss. Her prob-

lem first started with a generalized tonic clonic seizure fol-

lowing head trauma during sportsclassin school 9 months

ago. According to her parents’ report, she had about one

minute postictal phase after her first episode of seizure. She

was admitted to hospital and tooklamotrigin and pheny-

toin that were discontinued gradually by improvements of

her symptoms. Two month later, she developed ataxia, dif-

ficulties with walking and generalized weakness. At that

time, her neurological examinations revealed no abnormal-

ities except spastic tone of muscles and upward plantar re-

flex. Her blood biochemistry, urine analysis, and cerebro-

spinal fluid (CSF) study were all within normal limits except

for increased serum pyruvate level (2 mg/dl, normal: 0.3

- 0.7) and elevated CSF lactate (3.2 mmol/L; normal: 1.1-

2.3). In addition, urine copper, serum copper and cerulo-

plasminlevels were in normal range. Brain magnetic res-

onance imaging (MRI) showed symmetric bilateral hyper-

signal lesions in basal ganglia accompanied by isosignal le-

sions in splenium and corpus callossum (Figure1). Basal gan-

glia lesions were negative on diffusion weighted (DW ) while

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F. Ashrafi et al. 2

Figure 1: Bilateral basal ganglia hyper-intensities on brain mag-

netic resonance imaging (MRI).

splenium and corpus callossum were positive, restricted

with low apparent diffusion coefficient (Figure 2). Magnetic

resonance spectroscopy also reported an abnormal hyper

intensity with near symmetrical configuration in periven-

tricular region, brain stem and medulla with lactate rise

and diffusion restriction compatible with mitochondrial dis-

orders or glutaricaciduria.Electromyography/nerve conduc-

tion velocity (EMG/NCV ) revealed axonal polyneuropathy

with neurogenic changes without active denervation (Fig-

ure 3). Ophthalmology consultation was negative for retini-

tis pigmentosaand Kayser–Fleischer ring. With the impres-

sion of metabolic disease, she was treated with Co Q10, Vita-

min B1, L-Carnitine and B-complex (mitochondrial cocktail)

and dramatically responded to treatment and her neurolog-

ical conditions improved. She was discharged without any

complaint and suggested to come back to clinic with genetic

study report, complete treatment and follow up. Two weeks

later she presented to emergency room with respiratory dis-

tress. On admission, she was ill and not oriented. Her blood

pressure was 140/70 mmHg, pulse rate of 141/minute, res-

piratory rate of 45/minute, temperature 37.3◦Cand O2 sat-
uration 89%. Her arterial blood gas analysis revealed pH of

7.40, PaO2 of 60.2, PaCO2 of 27 and HCO3 of 16. General

examinations were normal except tachypneic breathing with

subcostal retraction. Her neurological examination was re-

markable for left eye deviation (abducent nerve paresia) and

generalized weakness. Her lower limb muscular force was

3/5. She was intubated and supportive therapy was begun for

her.She had cardiac arrest and died despite cardiopulmonary

resuscitation. Three days later, her genetic study revealed ho-

mozygote mutation (35 del G) in evaluation of entire coding

regions of GJB2 and confirmed the diagnosis of LS. A diag-

nosis of late-onset LS was made based on radiological and

response to mitochondrial cocktail.

Figure 2: Restriction of the lesions on diffusion weighted (DW )

brain magnetic resonance imaging(MRI).

Figure 3: Reduced amplitude of the right and left median motor

nerves on nerve conduction velocity (NCV ).

3. Discussion:

LS is categorized as a mitochondrial encephalomyelopathies.

Defect in enzyme pathway for respiratory metabolism has

been known as an underlying factor (6). In this case, the

most interesting aspect was the head trauma as a possible

precipitating factor in developing seizure and other symp-

toms in a previously normal child that finally led to diagnosis

of LS. Up to now, few cases have been reported who devel-

oped neurological disorders with underlying gene mutation

following head trauma. In 2010, Namekawa et al, reported an

adult onset of Alexander disease in a 60 year old man whose

symptoms initiated after head trauma (7). Furthermore,

Hayashi et al.presented a 34-year-old man who developed

a gradual visual problem about 6 months after an accident

and was finally diagnosed with Leber’s hereditary optic neu-

ropathy (8). Moreover, association between traumatic brain

injury and mitochondrial pathway defect has been shown

previously (9). Our case, together with previous case reports

raised the possibility of trauma being a precipitating factor

in developing or progression of mitochondrial disorders.

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3 Emergency. 2017; 5 (1): e43

4. Conclusion

This case showed the possible role of triggers such as head

trauma in developing LS in patients with underlying genetic

defect.

5. Appendix

5.1. Acknowledgements

The authors wish to thank all the staff of emergency and neu-

rology departments of ShohadayeTajrish Hospital, Tehran,

Iran.

5.2. Author’s contribution

The authors passed four criteria for authorship contribution

based on recommendations of the International Committee

of Medical Journal Editors.

5.3. Conflict of interest

None.

5.4. Funding

None.

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	Introduction
	Case presentation:
	Discussion: 
	Conclusion
	Appendix
	References