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Adult Form of Leigh's Disease: a Clinico Pathological Case with CT Scan Examination

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Adult Form of Leigh's Disease: a Clinico Pathological Case with CT Scan Examination J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.11.1211 on 1 November 1984. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1984;47:1211-1215 Adult form of Leigh's disease: a clinico pathological case with CT scan examination F GRAY,* F LOUARN,t R GHERARDI,* JF EIZENBAUM,t C MARSAULTt From Departement de Pathologie, * Service de Neurologie, t and Service de Neuroradiologie, t H6pital Henri Mondor, Creteil, France SUMMARY The clinical and pathological findings of a 31-year-old woman, in whom the diagnosis of Leigh's disease was made, are reported. CT scan examination with contrast enhancement showed symmetrical areas of low density, in both thalami, anterior limbs of internal capsules and corpus callosum. Longstanding chronic lesions involved the optic chiasma and the cerebral peduncles and consisted of myelin loss, status spongiosus, astrocytic gliosis and marked capillary proliferation. The neurons were spared. In the basal ganglia, internal capsules and corpus cal- losum, these lesions were more recent and consisted of focal necrosis, perivascular oedema and few lymphocytic perivascular cuffings. guest. Protected by copyright. Subacute necrotising encephalomyelopathy (Leigh's of the left upper lid, bilateral paresis of the 6th nerve, a disease) rarely occurs in adults: to our knowledge right facial palsy and a right extensor plantar response. The only 16 pathologically studied cases have been general examination was unremarkable. The patient reported'-9 and only one of these had computed seemed well nourished and showed no signs of chronic alcoholism. BP was 120/80 mmHg. CSF was normal on tomography.' This paper reports the clinical and two occasions; two days before death, it contained 68 mg/ pathological findings of an adult case in which the 100 ml protein, 18% y globulin. EEG showed non specific diagnosis of Leigh's disease was made. generalised slow waves. The CT scan revealed bilateral, ill defined areas of low density in both thalami and anterior Case report limbs of internal capsules (fig la, b). Parts of these lesions showed diffuse enhancement after contrast injection. Such A 31-year-old Chilean woman was admitted to hospital a contrast enhancement was also seen in the splenium of because of visual impairment and increasing stupor. The the corpus callosum (fig lc, d). family history was difficult to obtain because the patient The following investigations gave normal results: blood lived alone, did not speak French well and was stuporous. cell count, FSR, urea nitrogen, serum glucose, Na, K, P, She only could say that her mother was epileptic. The Ca, ceruloplasmin, antinuclear antibodies, viral antibodies, patient was not alcoholic. At the age of 21 years, she had parasite antibodies. suffered from an episode of confusion which lasted one From the first day of hospitalisation, intravenous 5% week and resolved spontaneously. Two months before then 10%, glucose infusion was administered with a vita- death, she developed intellectual slowing, behavioural min supplement containing 50 mg/day of thiamine. Four http://jnnp.bmj.com/ abnormalities and impairment of recent memory. One days before death, she received an additional intravenous month later, she experienced transient fever, headache and injection of 1 g/day thiamine hydrochloride. She deterior- nausea and over the following weeks, her mental state ated rapidly becoming increasingly drowsy. Chewing worsened; she had visual hallucinations, became stuporous movements became more marked. Neurological examina- and was admitted to the hospital. The patient could answer tion revealed bilateral pinpoint non-reactive pupils, com- when questioned; she frequently yawned and made chew- plex and variable disorders of eyes movements, bilateral ing movements. Neurological examination revealed ptosis facial palsy, generalised rigidity, brisk deep tendon reflexes and bilateral extensor plantar responses. One day before her rose to on September 25, 2021 by Address for reprint requests: Dr F Gray, D6partment de death, temperature 42°C without evidence of Pathologie, H6pital Henri Mondor, 51 av du Mal de Lattre de infection and she became deeply comatose. In spite of Tassigny, 94010 Creteil Cedex, France. attempt to resuscitate her, she died of acute respiratory failure 10 days after admission. Received 6 March 1984 and in revised form 3 May 1984. Accepted Post-mortem examination, 27 hours after death, revealed 5 May 1984. mild bronchopneumonia. The liver was normal. 1211 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.11.1211 on 1 November 1984. Downloaded from 1212 Gray, Louarn, Gherardi, Eizenbaum, Marsault guest. Protected by copyright. Fig 1 CT scan examination. (a, b) plain scan: ill defined low dense areas in both thalami and anterior limbs ofinternal capsules. (c, d) same levels after contrast injection: enhancement in both thalami and in the splenium ofthe corpus callosum. Neuropathological examination was performed after 20 Lesions clearly seen in sections stained for myelin, http://jnnp.bmj.com/ days of 10% formalin fixation. Blocks from many regions looked ill defined; they did not correspond to a vascular of both cerebral hemispheres, cerebellum, brainstem and territory and involved the upper part of the optic chiasma, spinal cord were embedded in paraplast or in cellofdin and the head of both caudate nuclei, the septum pellucidum, stained with haematoxylin and eosin, Loyez stain for the anterior limbs of both internal capsules, the anterior myelin, Bodian silver impregnation for axons combined parts of both thalami (fig 2a), the splenium of the corpus with Luxol fast blue and by the Gordon and Sweet method callosum, the superior and inferior colliculi and the peri- for reticulin. The brain weighed 1300 g. Gross examina- aqueductal region (fig 2b). A small focus of myelin loss was tion showed bilateral pale granular fresh necrotic lesions observed in the inferior part of the corpus callosum in its involving symmetrically the heads of the caudate nuclei, middle third. The cerebral cortex, centrum semi-ovale, the on September 25, 2021 by the internal capsules, the walls of the third ventricle and mammillary bodies, the anterior parts of the cerebral the thalami. Older greyish lesions were observed in the peduncles, pons, medulla, cerebellum and spinal cord were posterior parts of the cerebral peduncles. The optic unaffected. chiasma looked atrophic and greyish. The mammillary Microscopical examination showed two types of lesion. The bodies were normal macroscopically. first consisted of longstanding chronic changes involving J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.11.1211 on 1 November 1984. Downloaded from Adult form of Leigh's disease: a clinico pathological case 1213 ..e. ..;. a- ;Z w i. %, ^! .^.:: .. .. 8: .S : .i . \: i:. ;>. .r *' :. b fW ...e: .:i4=. iL! X _:: 0 gR- av guest. Protected by copyright. 7 . i. 1. I t q: ..W .p -1 *r' .<t 1.p 4 Fig 2 (a) Coronal section ofthe basal ganglia through the mammilary bodies. Loyez stain x 1: Necrotic, ill defined Fig 3 (a) Tegmentum ofthe cerebral peduncle at the level area involving both thalamus and internals capsules. Myelin ofthe third cranial nerve, nucleus. Haematoxylin and eosin loss is also present in the fornix and the inferior aspect ofthe x 16: spongiosis, gliosis and vascular proliferation. The corpus callosum. The mammillary bodies are spared. (b) neurons are spared or demonstrate central chromatolysis. Horizontal section ofthe cerebral peduncles. Loyez stain x (b) Thalamus haematoxylin and eosin x 16: necrosis with 1: myelin loss in the inferior colliculi and periaqueductal numerous lipid phagocytes, capillary proliferation with grey matter. perivascular lymphocytes. Absence ofhaemorrhages. the optic chiasm and the cerebral peduncles. They con- Discussion http://jnnp.bmj.com/ sisted of ill-defined areas of myelin loss, status spongiosus, astrocytic gliosis and marked capillary proliferation with Since the initial description by Leigh,'° more than a endothelial hyperplasia. The neurons when present, for hundred cases of subacute necrotising encephalo- example in the third nerve nuclei and in the periaqueductal myelopathy have been reported (for review, see grey matter, (fig 3a) were generally preserved but many David et Since the clinical and showed the changes of central chromatolysis. Axons were al"). picture relatively spared. The other type of lesion was more recent biochemical findings may vary, the diagnosis is and involved the basal ganglia, internal capsules, walls of based on the neuropathology. Biochemical studies of the third ventricle and the corpus callosum. These lesions have shown an abnormality of the metabolism on September 25, 2021 by consisted of focal necrosis associated with perivascular thiamine, though this is not linked to a single inher- oedema; many lipid phagocytes were present and few ves- ited molecular deficit. Four different metabolic dis- sels were cuffed by lymphocytes. However, the neurons turbances have been proposed as the cause of this were relatively spared. Capillary proliferation was marked. disease: (1) pyruvate carboxylase deficiency, (2) the No haemorrhages were seen (fig 3b). presence of a factor which inhibits thiamine J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.47.11.1211 on 1 November 1984. Downloaded from 1214 Gray, Louarn, Gherardi, Eizenbaum, Marsault pyrophosphate ATP phosphotransferase, (3) pyru- seem to be a criterion for separating the adult form vate
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