Letters to the Editor 531 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.5.531 on 1 November 1996. Downloaded from tumour was removed with an ultrasonic intervening areas were mostly spindle tumour arising from a single root m aspirator. A thin layer of tumour remained shaped and had a more bulky eosinophilic the lower cauda equina.4 In that case the attached to the conus. A good plane of dis- cytoplasm. Both components stained posi- tumour was completely excised. In the pre- section between the tumour and the surface tively for S-100 protein (figure, d). sent case complete excision was not possible of the conus could not be safely achieved. Electron microscopy showed that the due to adherence to the conus and multiple Postoperatively, she made a slow but tumour cells in the myxomatous nodules nerve roots. The early postoperative course steady recovery. She was relieved of low and those in the internodular areas had has, however, been satisfactory with relief of back and radicular . At follow up four elongated cytoplasmic processes, mostly pain and restoration of ambulation. months after surgery, there was an area of covered by a continuous external lamina. The MRI appearance is similar to that of numbness in the L4 dermatome on the Wide spaced collagen fibres (Luse bodies) other intrathecal extramedullary tumours. right. She had returned home, where she were also identified. Ependymoma, neurofibroma, and menin- looked after herself. Neurothekeomas most often occur in the gioma were the major differential diagnoses. The tumour specimen was an irregular, skin of the face and arms of young adults. Connective tissue myxomas have occa- soft, greyish portion of tissue 2-2 x 1-5 x They arise from small cutaneous nerve sionally been described as arising from 0 7 cm in size. Microscopically it displayed a branches and not from the major peripheral paraspinal muscle5 and from the vicinity of a multinodular structure, in which pale, . They are benign lesions which are facet joint.6 An intramedullary location has sparsely cellular islands were separated by cured by excision. Rare recurrences have also been described.7 The compact cellular connective tissue septa or bands of more been reported after incomplete resection. schwannomatous component, the positive compactly cellular neoplastic tissue (figure, Cutaneous neurothekeomas have been clas- staining for S-100 protein, and the ultra- c). The pale nodules had a myxomatous sified into cellular and myxomatous sub- structural appearances clearly distinguish the appearance composed of stellate or elon- types, the second arising at an older age.3 present tumour from connective tissue myx- gated cells in a strongly alcianophilic, Neurothekeomas have rarely been found oma. mucoid matrix. The tumour cells in the intrathecally. There is one report of the GEORGE F KAAR SAAD H BASHIR JAMES M N'DOW Department ofNeurosurgery PHILIP V BEST Department ofPathology LESLEY N GOMERSALL Department ofRadiology, Aberdeen Royal Hospitals NHS Trust, Aberdeen AB9 2ZB, UK

Correspondence to: Mr G F Kaar, Ward 40, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, UK. 1 Webb JN. The histogenesis of nerve sheath myxoma: report of a case with electron microscopy. jPathol 1979;127:35-7. 2 Angervall L, Kindblom LG, Haglid K. Dermal nerve sheath myxoma. A light and electron microscopic, histochemical, and immunohis- tochemical study. Cancer 1984;53: 1752-9. 3 Barnhill RL, Mihm MC Jr. Cellular neu- at, y J rothekeoma. A distinctive variant of neu- rothekeoma mimicking melanocytic X %. tumours. Am J Surg Pathol 1990;14: 113-5. -i ...4 4 Paulus W, Jellinger K, Pemeczky G. Intra- spinal neurothekeoma (nerve sheath myx- oma). A report of two cases. Am J Clin 4.. Pathol 1991;95:511-6. bV... 5 Tahmouresie A, Farmer PM, Stokes N. Paraspinal myxoma with com- POST GA0ODIA1341UDEr pression. Case report. J7 Neurosurg 1981;54: 542-4. http://jnnp.bmj.com/ 6 Bell WO, Gill A, Babiak T, et al. Epidural # myxoma causing compression of the cauda equina. Case report. Neurosurgery 1983;12: i 325-6. ,.l 7 Pasaoglu A, Patiroglu TE, Orhon C, Yildizhan A. Cervical spinal intramedullary myxoma in childhood. Case report. J Neurosurg AN» 1988;69:772-4. on September 26, 2021 by guest. Protected copyright. Voluntary facial palsy with a pontine ;* * . .. lesion Emotional voluntary dissociation is not far~~~~~~~~~~~~~~~~~~~ uncommon in patients with central facial palsies.'-3 The neuroanatomical basis of this dissociation is not well understood. A recent '- .. case report in this J3ournal suggested that a pontine could result in unilateral vol- $ jr 441.8$.. ,, untary facial palsy.4 We have recently had the opportunity to study a very similar syn- drome. p,,O. A teacher aged 57 was referred three days

'4~~~~~~~~~~~~~~~~~~0 after the onset of progressive neurological symptoms and signs that had included, in order, unsteadiness, dysarthria, dysphagia, and weakness of the right arm, leg, and face. (a) Sagittal T2 weighted MR image (TR = ms, = tumour 4500 TE 130 ms) showing distorting the On admission, the patient was awake, region of the conus (arrow). (b) Postgadodiamide injection Tl weighted MR image (TR = 450 ms, TE = 15 ms), showing tumour (black arrow) displacing conus (white arrow) anteriorly and dysarthric but not aphasic, and had normal laterally. (c) Photomicrograph (haematoxylin and eosin x 10) showing pale myxomatous nodules vision and oculomotor function. He com- separated by narrow septa. (d) Photomicrograph ( x 40) ofthe tumour stained with the plained of impaired swallowing and right immunoperoxidase method to demonstrate S-100 protein. Note the dark (positive) staining in nuclei facial weakness. Neurological examination and cytoplasmic strands. disclosed a right for vol- 532 Letters to the Editor J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.5.531 on 1 November 1996. Downloaded from untary innervation. The patient could nei- tary facial movements projects from the lat- ther whistle nor smile on command. By con- eral (area 4) via the genu of the trast, the patient had normal emotional and the cerebral peduncle to facial expression when smiling or laughing interneurons within the pontine motor facial (fig 1). Voluntary and emotional innervation which synapse on facial motor neu- of the upper were spared on rons. This corticonuclear pathway projects either side, consistent with a central facial bilaterally to neurons that innervate perior- palsy. There was a prominent central hemi- bital and frontal muscles and mainly con- of right arm and leg. Sensory exami- tralaterally to neurons innervating perioral nation was normal. and buccal muscles. As unilateral stem Brain MRI showed a single, semilunar lesions in the upper cause contralateral lesion of the left pons that was hyperintense voluntary facial paresis (this study and that on T2 weighted images and hypointense on of Topper et a14) the level of crossing of cor- Tl weighted images (fig 2). The lesion was ticonuclear fibres is probably just above or at sharply delineated medially by the pontine the level of the motor facial nucleus. raphe which was slightly bulged to the right The pathways for emotional innervation due to mild oedematous swelling. The lat- of the face are less clear. Reviewing the per- eral border of the lesion was convex and tinent medical literature,' ' we conclude that I-00!MT7 .7 reached the surface of the anterior brain- probably all patients with unilateral emo- stem, sparing the midpontine . tional facial palsy had lesions in the con- No additional cerebral lesions were tralateral forebrain. This excludes as possible detected. The involved area corresponds to pathways for emotional facial innervation the territory of the anteromedial and antero- those previously implicated which involve lateral group of the pontine which ipsilateral or bilateral projections and do not are branches derived from the basilar . include thalamic and cortical centres: (a) The localisation of the lesion is consistent from centromedial amygdala and bed with an affection of the corticonuclear and nucleus of stria terminalis via stria terminalis corticospinal tracts, , and or ventral amygdalofugal projection to hypo- pontocerebellar fibres as well as the medial thalamic preoptic region or mamillary lemniscus on the midpontine level. nuclei, on to ipsilateral motor facial nucleus A voluntary unilateral facial palsy with through the brain stem intact emotional expression may result from via dorsal longitudinal fascicle or median lesions of the motor cortex or corticonuclear forebrain bundle;68 10 (b) directly from the tract. An emotional facial palsy with pre- amygdaloid complex to the lateral reticular served voluntary facial innervation has been formation in the ipsilateral pontine tegmen- associated with lesions in the , tum, which in turn innervates the ipsilateral Figure 2 Detection of a single left paramedian , temporal lobes, frontal white ." 13 By contrast, we midpontine ischaemic lesion by MRI (1-5 matter, or supplementary motor cortex.' think that emotional facial innervation origi- Tesla, fast spin echo sequence) four days after Bilateral voluntary facial palsy with preserved nates in the amygdaloid complex and associ- the onset ofsymptoms. (A) axial T2 weighted emotional expression is typical of the Foix- ated limbic structures, travels through basal images(TRITE 3000185 ms); (B) coronal T2 Chavany-Marie anterior operculum syn- ganglia via the thalamus to the supplemen- weighted images(TRITE 3000185 ms). drome.' The present study confirms that tary motor area or premotor cortex and from voluntary facial palsy can result from a pon- there, possibly partially via the external tine lesion4 and seems to prove that the fibre rather than internal capsule, to the con- MARTIN TREPEL MICHAEL WELLER tracts subserving voluntary and emotional tralateral motor facial nucleus.'4 16 This JOHANNES DICHGANS facial innervation are still anatomically dis- model is compatible with contralateral emo- Department ofNeurology tinct in the upper pons-that is, just above tional facial palsy caused by lesions of the DIRK PETERSEN the the motor motor exter- Department ofNeuroradiology, level of facial nucleus. supplementary area, thalamus, University of Tubingen, Medical School, The pathways for voluntary facial innerva- nal capsule, basal ganglia, rostromedial tem- Tubingen, Gernany tion are fairly well understood.76 After pre- poral lobe, and ,' as http://jnnp.bmj.com/ processing of the motor impulses-for well as with isolated voluntary facial paresis within the basal and the after lesions of the contralateral motor cor- 1 Monrad-Krohn GH. On the dissociation of example, ganglia voluntary and emotional innervation in facial thalamus, the executive pathway for volun- tex (area 4) or internal capsule. paresis of central origin. Brain 1924;47: 22-35. 2 Karnosh LJ. Amimia or emotional of the face. Diseases of the Nervous System 1945; 6:106-8. 3 Hopf HC, Muller-Forell W, Hopf NJ. Localization of emotional and volitional facial paresis. 1992;42: 1918-23. on September 26, 2021 by guest. Protected copyright. 4 Topper R, Kosinski C, Mull M. Volitional type of facial palsy associated with pontine ischaemia. .7 Neurol Neurosurg Psychiatry 1995;58:732-4. 5 Weller M. Anterior opercular cortex lesions cause dissociated lower cranial nerve palsies and anarthria but no aphasia: Foix-Chavany- Marie syndrome and "automatic voluntary dissociation" revisited. _7 Neurol 1993;240: 199-208. 6 Brodal A. Neurological anatomy in relation to clinical medicine. New York: Oxford Uni- dz! versity Press, 1981 :498;733. 7 Jenny AB, Saper CB. Organization of the facial nucleus and corticofacial projection in the monkey: a reconsideration of the palsy. Neurology 1987;37: 930-9. 8 De Olmos JS. Amygdala. In Paxinos G, ed. The human nervous system. San Diego: Academic Press, 1990:583-7 10. 9 Heimer L. The humian brain and spinal cord. New York: Springer, 1995. 10 Holstege G. Some anatomical observations on the projections from the hypothalamus to brain stem and spinal cord: an HRP and autoradiographic tracing study in the cat. _7 Figure 1 Dissociated right centralfacial palsy with preserved emotional innervation five days after Comp Neurol 1987;260:98-126. the onset of symptoms. The patient exhibits voluntary facial palsy when trying to smile on command 11 Hopkins DA, Holstege G. Amygdaloid projec- (left) but has normal innervation on involuntary laughing (right) (with permission). tions to the mesencephalon, pons and Letters to the Editor 533 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.5.531 on 1 November 1996. Downloaded from

in the cat. Exp Brain Res 1978;32:529-47. 12 Price JL, Amaral DG. An autoradiographic study of the projections of the central nucleus of the monkey amygdala. J7 Neurosci 1981;1:1242-59. 13 Isokawa-Akesson M, Komisaruk BR. Differ- ence in projections to the lateral and medial facial nucleus: anatomically separate path- ways for rhythmical vibrissa movement in rats. Exp Brain Res 1987;65:385-98. 14 Kuypers HGJM. Corticobulbar connections to the pons and lower brain stem in man. An anatomical study. Brain 1958;81:364-88. 15 Russchen FT, Bakst I, Amaral DG, Price JL. The amygdalostriatal projections in the mon- key. An anterograde tracing study. Brain Res 1985;329: 1242-59. 16 Graybiel AM. The basal ganglia and the initia- tion of movement. Rev Neurol 1990;146: 570-74. 11ill.l 111.2 111.3 111.4 - 111.5 111.6 111.7 111.8

Brainstem involvement in Leber's hereditary optic neuropathy: associa- IV.1 IV.2 IV.3 IV.4 IV.5 IV.6 tion with the 14 484 mitochondrial DNA mutation Figure 1 Pedigree of the LHONfamily, showing a clear maternal transmission of the optic Leber's hereditary optic neuropathy neuropathy. Circle = female; square = male; oblique lines = deceased;filled symbols = affected; (LHON) is a maternally inherited disease open symbols = unaffected; arrow = patient. leading to severe bilateral visual loss. It has recently been associated with several mito- the dorsal (fig 2), and no other limbs and there was bilateral ankle clonus. chondrial DNA (mtDNA) point mutations. abnormalities. auditory evoked Plantar responses were flexor. He still had Three major primary pathogenic mutations potentials (BAEPs) and somatosensory combined vertical gaze ophthalmoplegia. are located at nucleotide positions 11 778, evoked potentials were normal. Results from Brain MRI showed a pronounced decrease 3460, and 14 484. Whether two other muta- analysis of CSF were normal. Standard in the size of the brainstem lesion. Results tions at positions 4160 and 15 257 are pri- blood tests showed a mild previously known from cervical and dorsal spinal cord MRI mary pathogenic mutations remains increase in liver function. Because of a past were normal. Again, symptoms improved controversial.' transient drug addiction, viral serological progressively, and six months later ataxia An association between LHON and vari- tests were performed and were negative for had partly resolved, tinnitus had almost dis- ous other neurological diseases has long hepatitis B and HIV, but positive for hepati- appeared, and ophthalmoplegia was limited been suggested. However, non-fortuitous tis C. Serum thiamine concentration was to a downgaze paresis. One year later, clini- combinations of neurological disorders and normal. cal features and brain MRI were unchanged. genetically established LHON seem to be In September 1992 and January 1993, he DNA was extracted from venous blood by rare. Most of them are cases of "multiple had subacute worsening of his symptoms, standard techniques and analysed for the sclerosis-like" illness in patients with LHON leading eventually to global gaze palsy and mtDNA mutations at positions 3460, 4160, with the 11 778 or 3460 mtDNA muta- bilateral tinnitus. The brainstem lesion was 11 778, and 15 257 using the polymerase tions.2 We report a case of brainstem larger on MRI (fig 2). His BAEPs showed chain reaction (PCR) and restriction involvement in a patient with LHON har- prolongation of the I-III interpeak interval. endonuclease digestion, as previously bouring the 14 484 mtDNA mutation, and Other investigations were normal. During described.3 The T to C mutation at position none of the other above mentioned muta- the subsequent months, symptoms 14 484 was detected using PCR ampli- tions. improved spontaneously. In January 1994, fication of a 115 bp segment spanning A 30 year old man (IV-5) had a strong he complained of stiffness of both legs. On the mutation site, with oligonucleotide http://jnnp.bmj.com/ family history of LHON. This disease was examination, he had a moderate spastic primers 14 390-14 419 (forward) and diagnosed by academic ophthalmologists in ataxia. Tendon reflexes were very brisk in all 14 513-14 486 (reverse). The reverse six other members of his family (fig 1). Four primer was modified by introduction of a of them (III.2, III.4, III.5, IV.3) were young mismatch (substitution of A for C at posi- at onset (9 to 14 years of age) and had good tion 14 487) in the wild type sequence. This recovery of vision. None had a neurological creates a restriction site for Bsr I in mutant complaint. Patients III.4 and IV.1 were per- mtDNA. The patient harboured the 14 484 seen: examination and mutation and was heteroplasmic for it sonally neurological on September 26, 2021 by guest. Protected copyright. brain MRI were normal in both. (- 70% of mutant mtDNA). He did not At the age of four years, the patient had harbour any of the four other mutations. bilateral visual loss, which never recovered. Members III.4 and IV.1 were tested for the At the age of 16, he had vertigo, dizziness, 14 484 mutation. They were also hetero- and vomiting that were diagnosed as "cen- plasmic (- 70% of mutant mtDNA in tral vestibular disorder" at the local hospital. both). Symptoms resolved spontaneously, but In the present family, four of the seven recurred 10 years later. In April 1992, he affected members had a young age of onset experienced difficulty in looking down, pro- and good recovery of vision, whereas three gressing over 48 hours. Vertical gaze palsy did not recover. A good recovery of vision was noted by local neurologists. Cranial CT has often been reported in patients with was normal. The diagnosis of multiple scle- LHON harbouring the 14 484 mutation.' It rosis was suspected and the patient received seems to be strongly correlated with an early intravenous methylprednisolone, with no age of onset and not with the degree of het- benefit. He was admitted to our department eroplasmy in affected members. in July 1992. Visual acuity was 1/10 OD and Paradoxically, our patient had the earliest 4/10 OS. There was bilateral optic atrophy. age of onset but did not recover. He was the He had a combined vertical gaze ophthal- only one that experienced symptoms of moplegia, bilateral eyelid ptosis, and bilat- CNS involvement. In fact, it is the first time eral gaze evoked nystagmus. His that the 14 484 mutation has been unequiv- neurological examination was otherwise nor- ocally associated with CNS involvement in a mal. Figure 2 Axial T2 weighted MRI, showing a patient with LHON, although this mutation Brain MRI showed a symmetric area of symmetric lesion of the dorsal midbrain has already been reported in an LHON increased signal on T2 weighted images in (maximum size, January 1993). pedigree with neurological features. A large