48ournal ofNeurology, Neurosurgery, and Psychiatny 1995;59:438-441

SHORT REPORT

Thalamo-olivary degeneration in a patient withlaryngopharyngeal dystonia

Toru Yamamoto, Mariko Yamashita

AbstractA 67 year old woman with a two year his-tory of laryngopharyngeal dystonia, spas-modic dysphonia, and parkinsonismsuccumbed to Wernicke's encephalopathyand died six months later. Necropsyshowed, besides Wernicke's encephalo-pathy, degenerative changes in selectedthalamic nuclei (dorsomedial, pulvinar,and the medial geniculate bodies) and theinferior olives and numerous cerebellartorpedoes. The substantia nigra and basalganglia were spared. Immunostaining forprion protein was negative. This patientindicated a new type of presentation ofso-called pure thalamic degeneration, ormore precisely thalamo-olivary degener-ation.

(J Neurol Neurosurg Psychiatry 1995:59;438-441)

Keywords: thalamo-olivary degeneration; thalamicdegeneration; spasmodic dysphonia; laryngopharyngealdystonia

Department ofNeurology, OsakaSaiseikai NakatsuHospital, Osaka, JapanT YamamotoM YamashitaCorrespondence to: Dr ToruYamamoto, Departnent ofNeurology, Osaka SaiseikaiNakatsu Hospital, 2-10-39Shibata, Kitaku, Osaka 530,Japan.Received 23 March 1995and in final revised form20 June 1995Accepted 20 June 1995

Thalamic degeneration is a rare condition, theclinical manifestations of which have beenvariable cognitive memory and behaviouraldisorders.' Three types of selective thalamicdegeneration have been distinguished' 2:firstly, combination with a variety of neuro-

degenerative3-5 and metabolic disorders suchas Menke's kinky hair disease; secondly, thethalamic form of Creutzfeldt-Jakob disease2;thirdly, isolated or pure thalamic degenera-tion.2 6" Now that a mutation at codon 178 ofthe prion protein gene has been detected infatal familial insomnia'4 15 that used to belongto the third category,2 13 these patients maywell be recategorised to the second or priondisease group despite different clinical mani-festations. Therefore the patients with purethalamic degeneration who were negative or

not tested for prion protein were onlyseven2 6-1; among these were four Japaneseand one Chinese; and two of the seven

patients were familial. The thalamic involve-ment has been roughly selective among itsdivisions and there has been no patient inwhom the thalamus was the only site of degen-eration. Interestingly, degeneration of the

inferior olives accompanied the thalamicchanges not only in all the patients with purethalamic degeneration except one7 but also inpatients with prion disease. The olivary degen-eration is associated with no2 6 7 or mild8-"cerebellar cortical changes; thus a trans-synap-tic degeneration was unlikely. Therefore wethink that the term thalamo-olivary degenera-tion is more appropriate to designate thiscondition.We experienced such a patient with

thalamo-olivary degeneration, who presentedmainly with parkinsonism, dystonia, and spas-modic dysphonia.'6 '7 Our patient was the firstin whom spasmodic dysphonia was one of themain features and the thalamic and inferiorolivary lesions were confirmed at postmortemexamination.

Case reportA 67 year old independent woman ex-typistwho had had a partial gastrectomy for gastriccancer at the age of 65 gradually developedgait disturbance and involuntary laryngopha-ryngeal movements with a component of spas-modic dysphonia over 18 months. Her familyhistory was not relevant. She had been livingalone and her relatives had noticed subtleabnormalities in her behaviour after thesurgery. For example, she refused gifts of foodbased on her assumption that it was old andshe removed the petals from arranged flowersto detect presumed insects. Because ofincreasing anorexia and discomfort whenbreathing the patient was again admitted toour hospital in December 1992. There was noevidence of recurrence of cancer or presenceof other disorders to account for her loss ofappetite and a neurological consultation wasmade. Her mental state was unremarkableexcept for depression; and she scored 28/30 onthe mini mental state examination. Cranialnerves were intact and swallowing was not dis-turbed. There was moderate parkinsonismwith hypokinesia, cogwheel rigidity of thelimbs, neck, and trunk, a mask-like face, and ashuffling gait. Tremor was absent and posturalresponse was intact. Tendon reflexes werenormal and the plantar response was flexor.There were involuntary movements in thethroat muscles that were characterised byirregular abrupt stops in the inhalation phase,

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Thalmo-olivary degeneration in a patient with laryngopharyngeal dystonia

producing faint unintentional phonation.These abnormalities were confirmed by pneu-motachogram (fig 1). Fibre laryngoscopy alsoshowed irregular, repetitive, vocal fold closingduring the resting state of respiration. Syn-chronous with the unintentional phonationwas raising of her throat as if to swallow, nod-ding-like neck flexion, and slight forwardbending of the trunk. Ataxia was not evident.Brain CT was normal. Levodopa up to 400mg/day with a decarboxylase inhibitor and anantidepressant were tried without an appre-ciable effect.

Fluid infusion without supplementation ofvitamins induced Wernicke's encephalopathyin April 1993. Thereafter, no more spas-modic dysphonia, dystonia, or dyskinesia wasobserved. Although the patient partially recov-ered, she was kept confined to bed and hermental state deteriorated again five monthsafter the attack of Wernicke's encephalopathy.Eventually she entered a state of akinetic

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Figure 1 Pneumotachogram showing abrupt involuntary interruption (dots) ofinhalation during normal respiration. At these points the patient producedfaintunintentional phonation. A mask was worn by the patient and normal control and airflowwas measured with the same calibration.

Figure 2 Severe neuronloss and isomorphic gliosisin the dorsomedial bodyof the thalamus;haematoxylin-eosin.Bar represents 100 um.

mutism. Her ECGs showed background disor-ganisation with diffuse theta and delta slowing:no periodic sharp discharges'8 were recordedon any occasion. She died two months later ofuncontrollable respiratory infection in October1993.Postmortem examination showed broncho-

pneumonia and widespread microabscess for-mation. There had been no recurrence ofcancer. The brain weighed 1140 g. Macro-scopic abnormalities were limited to thenecrotising lesions around the third ventricleand the aqueduct and a mild atrophy of themammillary bodies. Histological examinationconfirmed tissue destruction with macro-phages and hypertrophic astrocytosis, whichwas consistent with Wernicke's encephalo-pathy. There was severe thalamic degenerationdistinct from the changes of Wernicke'sencephalopathy, consisting of isomorphicfibrillary gliosis and loss of neurons (fig 2).The dorsomedial, pulvinar, and the medialgeniculate bodies were mainly affected bilater-ally (fig 3). The anterior nuclei were mostlypreserved. The superior and inferior colliculiwere moderately gliotic. The inferior olivesand the accessory olivary nuclei showed severedegeneration (fig 4). Although the cerebellarcortex escaped neuron loss, there were profusetorpedoes (fig 5). A few Lewy bodies wereseen in the pigmented brainstem neurons.Otherwise, the basal ganglia, substantia nigra,subthalamus, the rest of the brainstem, andthe spinal cord were intact except for scatteredmicroabscesses and mild gliosis. A fewAlzheimer's neurofibrillary tangles were seenin the hippocampus and senile plaques or bal-looned neurons were not detected. Spongychanges characteristic of Creutzfeldt-Jakobdisease were not found and immunostainingfor prion protein was negative.

Discussion"Pure" thalamic degeneration, even in itsbroad sense, has been reported in only a fewcases.2 $1- 14 The precise mapping of subdivi-sional thalamic involvement in these patientsis hampered by variable nomenclature.According to the standard text of Carpenterand Sutin'9 and the schematic illustrations inthe medical literature, the most consistentaffected regions were dorsomedial, anterior,ventral anterior, and pulvinar. Our patient wasunique both in the affected medial geniculatebody, that was intact in all except one patientreported by Hori et al,'0 and the spared ante-rior nuclei, that were always affected in otherpatients described. The constant involvementof the inferior olives in pure thalamic degener-ation is a peculiar finding as there is no directfunctional connection between these twostructures. Of related interest both in purethalamic degeneration and in prion diseasewere minor cerebellar changes that includedtorpedoes of the Purkinje cell axons,3 11-1320which are not specific,21 but are intriguingaccompaniments.

There were patients with multiple systemdegeneration in which thalamic changes were

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Yamamoto, Yamashita

Figure 3 Schema ofthalamic degeneration(black) and Wernicke'sencephalopathy (stippled).Senial coronal sections fromthe right caudal (top left),through the rostral, to theleft caudal (bottom right)portions.A= anterior;Ca = caudate;CM = centromedian;DM = dorsomedial;GP = globus pallidus;IC = internal capsule;LD = lateral dorsal;LGB = lateral geniculatebody;LP = lateral posterior;Mam = mammillary body;Midl = midline;MGB = medial geniculatebody;OT = optic tract;PF = parafascicular;Pulv = pulvinar;Put = putamen;Ret = reticular;RN = red nucleus;SC = superior colliculus;SN = substantia nigra;Sth = subthalamus;VA = ventral anterior;VL = ventral lateral;VP = ventral posterior.

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disproportionally severe. These patients3 4 22were not different in the distribution patternof thalamic lesion from patients with puredegeneration. Similarly, cases of the thalamicform of prion protein disease showed changesindistinguishable from pure cases. A normalprion protein gene but positive prion proteinimmunoblot were seen in one patient withmild spongiform encephalopathy.'2 Wernicke'sencephalopathy is another disorder in whichthe thalami, particularly the dorsomedial andpulvinar areas, are always involved.23 Involve-ment of the anterior nucleus is frequent,whereas that of the medial geniculate body isuncommon in Wernicke's encephalopathy:both of these are contrary to the findings inour patient. Furthermore, olivary degenerationis not a part of Wemicke's encephalopathy.

Clinical presentation of this patient wasdistinct from the other reported cases and

indicates a wide clinical range of thalamicdegeneration despite rather uniform pathologi-cal findings. Spasmodic dysphonia is a termthat describes a family of strained, strangledvoices, voice tremor, or stridor, resulting fromvocal fold spasm."' 17 Three types adductor,abductor, and mixed-of spasmodic dyspho-nia are known, among which the adductortype is by far the most common. For dystoniain general, there has been uncertainty as to theunderlying pathology. Not infrequently psy-chogenic dysfunction (psychoneurosis) is theonly explanation for spasmodic dysphonia.24Pool et al,'6 however, found neurologicalabnormalities in about 70% of their patients.Disturbed rapid alternating movements, weak-ness, and tremor were some of the abnormali-ties. The authors suggested, from anatomicaland functional brain imaging studies, that thepallidothalamic area (pars oralis of the ventro-

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Thalmo-olivary degeneration in a patient with latyngopharyngeal dystonia

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lateral nucleus of the thalamus)-the supple-mentary motor area-could account for theneurological findings. Rosenfield et al17 evalu-ated 100 patients with spasmodic dysphoniaand showed that 71 had essential tremor, 25had Meige's syndrome, and 12 were hypothy-roid. Among the reported patients with thala-mic degeneration only one8 had abnormalphonation: she showed strong inspiratoryeffort due to whoop-like laryngeal spasms.Even this patient's sign was unlike the rhyth-mic spasmodic dysphonia of our patient, whoshowed nodding-like neck movement andpharyngeal components.

Regarding other clinical signs in thalamicdegeneration, particularly different in our

patient was an apparent absence of bothdementia at the early stages and sleepdisturbance. Superimposition of Wemicke's

encephalopathy could have terminated thenatural course of the disease, muting theseimportant signs and making the laryngopha-ryngeal dystonia disappear. The necrotisingchanges in Wernicke's encephalopathy couldpossibly interrupt neural circuits underlyingthe movement disorder as in surgical proce-dures for tremor.

We thank Dr Jun Tateishi of Kyushu University for the prionprotein study and Yuri Fujiwara, speech therapist of our hospi-tal, for evaluating speech dysfunction.

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