206 Letters to the Editor dysarthria is usually associated with other infarcts: a clinical-magnetic resonance imag- the subcortical region of the right cerebellar J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.2.206 on 1 August 1996. Downloaded from ing correlation study. Ann Neurol 1993;33: hemisphere. Brain MRI showed no vascular symptoms, such as vomiting, limb , or 451-6. axial lateropulsion. 5 Silveri MC, Leggio MG, Molinari M. The malformation near the haematoma, but an In posterior inferior cerebellar artery and contributes to linguistic produc- MR angiogram (base view) showed abnor- anterior inferior cerebellar artery territory tion: a case of agrammatic following a mal dilatation of the basilar artery and right cerebellar lesion. 1994;44: infarcts dysarthria is an unusual symptom.4 2047-50. absence of the internal carotid arteries. Both There were no detailed phonetic descrip- anterior cerebral arteries and middle cere- tions in the cases reported, and brain stem bral arteries were filled from the enlarged signs were present as well. So, it might be posterior communicating arteries. Trans- suspected that his speech impairment femoral cerebral angiography showed no resulted from an involvement of brain stem bifurcation of either common carotid artery structures. Bilateral internal carotid artery agene- and absence of bilateral internal carotid Lechtenberg and Gilman2 first noted that sis arteries. The ophthalmic arteries were sup- dysarthria developed most often after dam- plied through the middle meningeal artery. age extending into the superior paravermal Bilateral internal carotid artery agenesis is Left vertebral angiography showed an segments of the left cerebellar hemisphere. extremely rare. Agenesis of the internal enlarged and tortuous basilar artery. A high Amarenco et al3 confirmed this finding in a carotid artery may cause cerebrovascular resolution CT of the skull base showed com- patient with an isolated cerebellar dysarthria diseases such as subarachnoid haemorrhage plete absence of the carotid canals on both after a small infarction in the left paravermal or cerebral ischaemia. We describe a patient sides, indicating bilateral internal carotid zone; but they considered a minute mirror with bilateral internal carotid artery agenesis artery agenesis. image lesion to be of no importance, the manifesting as intracerebellar haemorrhage. The patient gradually improved with con- patient's hand dominance was not reported, A 57 year old woman suddenly developed servative medical treatment and was dis- and MRI was not performed. Nevertheless, vertigo and vomiting with severe headache, charged on 13 December with no both studies strongly implicated the left and was brought to our hospital by ambu- neurological deficit. She died suddenly at cerebellar hemisphere in the development of lance on 19 November 1993. She was alert home of heart failure on 30 January, 1994. dysarthria. Ackermann et al I did not corrob- with slight ataxia on the right side. Brain CT Congenital internal carotid artery agenesis orate the notion of an exclusive left sided showed a haematoma 2 cm in diameter in is a very rare anomaly, with only about 100 paravermal cerebellar speech cortex; three of the four dysarthric patients in their study had unilateral right sided ischaemia due to occlusion of the superior cerebellar artery; all of them were right handed. The fourth had a bilateral cerebellar infarction. More recently, increasing evidence sug- gests a role for the cerebellum in cognitive functions such as language. Silveri et all reported a patient with agrammatical speech after a posterior inferior cerebellar artery infarction, suggesting a right cerebellar hemispheric dominance for language func- tion. It is not clear if that hemispheric domi- nance exists for speech function. The well delineated lesion in our patient agrees with the hypothesis that the right cerebellar hemisphere is the most likely site for cerebellar speech function as cerebro- cerebellar connections are predominantly contralateral and the left cerebral hemi-

sphere is dominant for speech function in http://jnnp.bmj.com/ right handed people. However, it may also Figure 1 Left: CT showing a haematoma in the subcortical region ofthe right cerebellar hemisphere. be possible that the site of the infarct (the Right: High resolution skull base CT showing complete absence of the carotid canals on both sides. paravermal zone) is more important than the side. In conclusion, as well as describing an exceedingly uncommon clinical presentation of a superior cerebellar artery infarction, our report suggests the superior right paravermal zone as the possible site of the cerebellar on September 30, 2021 by guest. Protected copyright. speech centre, and supports the hypothesis of functional interrelation between supraten- torial structures and cerebellum in func- tional domains outside the motor system. A GIRONELL Department ofNeurology, Hospital de la Santa Creu i Sant Pau, A ARBOIX Department ofNeurology, Hospital Central-La Alianfa, JL MARTI-VILALTA Department ofNeurology, Hospital de la Santa Creu i Sant Pau, Auwnomous University ofBarcelona, Barcelona, Catalonia, Spain Correspondence to: Dr A Gironell. 1 Ackermann H, Vogel M, Petersen D, Poremba M. Speech deficits in ischaemic cerebellar lesions. JNeurol 1992;239:223-7. 2 Lechtenberg R, Gihnan S. Speech disorders in cerebellar disease. Ann Neurol 1978;3: 285-90. 3 Amarenco P, Chevrie-Muller C, Roullet E, Bousser MG. Paravermal infarct and isolated Figure 2 MR angiogram (base view) showing abnormal dilatation of the basilar artery (large cerebellar dysarthria. Ann Neurol 1991;30: arrow) and absence of the bilateral ICAs. Both anterior cerebral arteries (small arrow heads) and 211-3. were the 4 Barth A, Bogousslavsky J, Regli F. The clinical middle cerebral arteries (large arrow heads) filledfrom enlargedposterior communicating and topographic spectrum of cerebellar arteries (small arrows). Letters to the Editor 207 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.61.2.206 on 1 August 1996. Downloaded from patients described since the first description rhage might be caused by haemodynamic 101-7) U/ml. Samples were assayed in dupli- in 1787.' In most cases, agenesis is unilat- stress. cate and the intraassay coefficient of vari- eral, with only 26 reported cases of bilateral The prognosis for internal carotid artery ance was 9 3%. Antibody to human AChR agenesis. Most of the early cases were dis- agenesis is unknown, because of the lack of was measured by immunoprecipitation. The covered by cadaver dissection. In 1972 detail in previous reports. Our patient died antigen used was human AChR purified Boudin reported the first living patient with of heart failure, but no necropsy was permit- from rhabdomyosarcoma cell line TE 671. bilateral internal carotid artery agenesis, ted. Her death may have been related to the The normal value (mean + 3SD) was based on an angiographical diagnosis.2 recurrence of cerebrovascular disease. 0- 12 nM. Intra-assay coefficient of variance on the ICHIRO SUNADA was 9 0%. There is no agreement development Department ofNeurosurgery, of the common carotid artery and its two Saiseikai Ibaraki Hospital, Ibaraki, Japan The sIL-2R correlated negatively with branches, the internal carotid artery and the TSUYOSHI INOUE antibody titre to human AChR (figure; external carotid artery. The two theories for Department ofNeurosurgery, r = 0-588, P < 0-01). Thymic histology the embryogenesis of these arteries are that Tane General Hospital, Osaka, Japan showed an association with sIL-2R concen- the common carotid artery and the proximal Correspondence to: Dr Ichiro Sunada, Depart- tration (one way ANOVA, p < 0 025), but parts of the internal carotid artery and exter- ment of Neurosurgery, Saiseikai Ibaraki Hospital, the Osserman clinical type did not. The sIL- nal carotid artery arise together from the Ibaraki, Japan. 2R in patients with thymoma (317-2 (64-1) third aortic arch; or that only the proximal 1 Tode. Medizinisch chirurgische bibliothek U/ml) was significantly lower than in the part of the internal carotid artery arises from (Kopenhagen)1787;10:408. Cited by: Fisher normal subjects, or patients with atrophic the third aortic arch, and the common AGT. A case of complete absence of both or normal thymus (535 7 (174-1) U/ml; internal carotid arteries, with a preliminary Scheffe test, P < 0 025), but not signifi- carotid and external carotid arteries arise note on the developmental history of the from the aortic sac.4 stapedial artery. JAnat 1914;48:37-46. cantly lower than in patients with hyperpla- Agenesis and hypoplasia should be differ- 2 Boudin G. Bilateral aplasia of the internal sia (426-2 (126-6) U/ml). All four patients entiated. Agenesis is the complete develop- carotid artery. Rev Neurol (Paris) 1972;127: with a high concentration of sIL-2R (more 329-40. + mental failure of an organ and its 3 Quint DJ, Silbergleit R, Young WC. Absence than mean 2SD) had a low AChR anti- primordium, whereas hypoplasia is the of the carotid canals at skull base CT. body titre (< 1 nM). incomplete development of a structure. The Radiology 1992;182:477-81. Some publications12 have shown a posi- 4 Lie TA. Congenital anomalies of the carotid between sIL-2R and disease primordial internal carotid artery is well arteries. Amsterdam: Excerpta Medica, 1968: tive correlation defined by the fourth embryonic week, 44-9. activity in , which does not whereas the skull base does not form until coincide with our result. It is also well estab- the fifth to sixth weeks of fetal life. lished that patients with myasthenia gravis Therefore, if the embryonic primordium of with thymic hyperplasia or thymoma have a the internal carotid artery fails to develop higher titre of AChR antibody than patients (agenesis), no internal carotid artery is pre- with a normal thymus. According to our sent when the skull base is formed, and no results of the negative correlation pattem of carotid canal develops. By contrast, a rela- Possible distinct pathogenesis in low sIL-2R with AChR antibody titre and the tively mild or relatively late insult occurring responder myasthenia gravis: associa- association of sIL-2R with thymic abnormal- in the course of development of the skull tion of soluble interleukin-2 receptor ity in myasthenia gravis, it is not likely that base portion of the internal carotid artery with acetylcholine receptor antibody sIL-2R is merely a T cell activation marker, will result in a hypoplastic internal carotid titre or abnormal thymus because AChR antibody production is T cell artery within a hypoplastic carotid canal.' dependent. Therefore, agenesis and hypoplasia of the In myasthenia gravis there is an increase in The problem is to decide what the patho- internal carotid artery can be differentiated soluble interleukin-2 receptor (sIL-2R), genic mechanism is in seronegative patients. by the demonstration of the carotid canal in which is associated with cellular immunity. Mossman et al showed that the immuno- the skull base. Some authors have confused Confalonieri et al' showed that the concen- globulin from seronegative patients with agenesis with hypoplasia, and carotid canals tration of sIL-2R correlated with the severity myasthenia gravis could induce impairment or internal carotid arteries were found in or the activity of the disease, and that there of chemical transmission at neuromuscular their patients. was no association of sIL-2R concentration junctions in mice.4 Cohen-Kaminsky et at The anterior cerebral circulation is most with antibody to fetal calf acetylcholine pointed out that the group of patients with commonly supplied through enlarged basilar receptor (AChR). On the other hand, myasthenia gravis with low AChR antibody http://jnnp.bmj.com/ and posterior communicating arteries in Cohen-Kaminsky et at2 reported a progres- titre seemed to represent a particular sub- patients with agenesis of the internal carotid sive decline of sIL-2R in myasthenia gravis group of the disease, which might be associ- artery. Occasionally an abnormal trans-sellar after thymectomy which correlated with the ated with a pathogenic mechanism involving anastomosis or an anastomosis between the clinical outcome. To elucidate the patho- AChR antibody produced in undetectable external carotid and intracranial systems genesis and cellular immunity in myasthenia amounts but especially pathogenic provide collateral flow. Brain CT or MRI gravis, we studied sIL-2R concentrations in antibody.2 We previously reported that ocu- can demonstrate the enlarged abnormal ves- 32 patients before immunosuppressive treat- lar myasthenia gravis had a different genetic sels. In our patient, MRI showed abnormal ment. background from generalised myasthenia dilatation of the basilar artery and absence All 32 patients (eight male and 24 female) gravis: the ocular type showed a low AChR on September 30, 2021 by guest. Protected copyright. of the internal carotid arteries. Therefore, participating in this study were older than 6 antibody titre and no antinuclear antithy- MRI is a useful diagnostic tool for this dis- years (mean 31-7 (range 7 to 72) years at ease. Especially, MR angiography can show onset), because sIL-2R concentration has the further relation between anterior and been reported to be higher in healthy infants posterior cerebral circulation clearly. This is under 6 years old than in adults.3 The num- 4 the first report to describe the value of MR ber of patients with type I, IIa, Ilb, or III Cc a a I r = 0-588 angiography. myasthenia gravis, according to Osserman's 0

Agenesis of the internal carotid artery may classification, was 12, 10, five, and five 0 2 0a 0 mainly cause cerebrovascular disease. Pre- respectively. The thymus was examined for C vious manifestations included subarachnoid abnormality by CT, and thymectomy was 0 haemorrhage in seven patients, cerebral performed on 21 patients, including one 0 0 0 ischaemia in five, seizure in three, brain whose thymus was atrophic. All thymuses E tumour in intracerebral in were after removal, 'o0 0~~ two, haemorrhage categorised histologically o * S one, chronic subdural haematoma in one, as thymoma, hyperplasia, atrophy, or nor- 0 syncope in one, cancer in one, and cardiac mal. Patients' serum samples were frozen at .0n -2 anomaly in one. Ours is the first patient to -70°C until assayed for sIL-2R and anti- , present with intracerebellar haemorrhage. body to AChR. The sIL-2R was measured 200 400 600 800 1000 The haematoma was located in the subcorti- by the cellfree interleukin-2 receptor bead- slL-2R (U/ml) cal of the cerebellar hemisphere, and kit cell C Cambridge portion assay (T diagnosis Ltd, Correlation between sIL-2R and antibody titre there was no lesion near the haematoma. MA, USA) using two monoclonal antibodies to human AChR. Correlation was assessed in Spontaneous haemorrhage of the cerebellum directed against two different epitopes on 28 patients in whom AChR antibody was usually occurs in the dentate nucleus region. IL-2R. The normal value of sIL-2R mea- detected. The concentrations ofsIL-2R in four In this case the location of the haematoma sured in serum samples obtained from 110 patients without AChR antibody were 475, was unusual, suggesting that the haemor- unrelated healthy controls was 390 7 (SD 419, 785 and 516 Ulml.