Hamann, Gerhard F.

Kalla, R.

Mayer, T.

English

Roger Kalla

Thomas Mayer

Gerhard F. Hamann

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Bilateral Anterior Inferior Cerebellar Artery Territory Brachium pontis Infarcts of Probable Hemodynamic Cause

Universität München: Elektronischen Publikationen

Bilateral anterior inferior cerebellar artery territory brachium pontis infarcts of probable hemodynamic cause

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Short Reports 233jected to PMF that uses matrix-assisted laser desorption ionization/time-of-flight mass spectrometry system (Voyager-Elite Biospec-trometry Workstation, Applied Biosystems) combined with sequencedatabase searches (MS-fit) (fig. 2C) and partial amino acid sequenc-ing with automatic peptide sequencer (Model 492HT, Applied Bio-systems) after digesting the proteins on 2-DE gels with endoproteaseLys-C [5]. Protein identification by PMF showed that the 49-kDaprotein was ·-enolase (fig. 2C). Meanwhile, the partial amino acidsequencing retrieved the sequences PDDPS and YON, correspond-ing to codons 264–268 and 407–409 of ·-enolase, respectively(fig. 2D).DiscussionThe patient reported here presented progressive sensorimotorneuropathy and encephalopathy with changes in personality, dis-turbed consciousness and cognitive decline associated with occultgastric adenocarcinoma. His sera contained antineuronal autoanti-body that labeled the patient’s carcinoma tissue and specificallyreacted with a 49-kDa protein in the mouse brain. We biochemicallyidentified this 49-kDa protein as ·-enolase. Although it has still notbeen proven that the anti-·-enolase antibodies in the patient’s serumhave anything to do with his sensorimotor neuropathy and encepha-lopathy, we consider that the anti-·-enolase antibodies are likely tocontribute to his multifaceted neurological disturbances for the fol-lowing reasons: his neurological symptoms temporarily went intoremission with IVIg therapy that may have blocked the harmfulaction of autoantibodies and, furthermore, his symptoms improveddramatically and were not exacerbated again after removal of his gas-tric adenocarcinoma which cells intensely expressed ·-enolase intheir cell bodies, which were immunoreacted with the patient’sserum.·-Enolase is one of the subunits of mammalian enolase, a glyco-lytic enzyme, and expressed ubiquitously [6]. Some may argueagainst our interpretation that anti-·-enolase antibody emerging inassociation with gastric cancer specifically caused disturbances con-fined to the nervous system, because ·-enolase is a ubiquitouslyexpressed enzyme. Usually organ-specific autoimmune diseases havetissue-specific enzymes as target autoantigens [7]. However, like eno-lase, other ubiquitously expressed enzymes have been associatedwith organ-specific autoimmunity, for example, dihydrolipoamideacetyltransferase is an autoantigen in primary biliary cirrhosis [8].Furthermore, there have been a few reports that ·-enolase was thetarget antigen that reacted with autoantibodies detected in cancer-associated retinopathy [9] and Hashimoto’s encephalopathy [10].The patient presented here had occult gastric adenocarcinomathat is uncommon in paraneoplastic neurological syndromes, but ithas been reported that gastric adenocarcinoma may be associatedwith paraneoplastic encephalopathy that usually precedes the diag-nosis of cancer [11]. Furthermore, insofar as we are aware, this is thefirst report that shows ·-enolase may be associated with paraneoplas-tic encephalomyelitis in the setting of gastric cancer. We would alsolike to emphasize that PMF combined with 2-D PAGE is an easy anduseful technique in identifying autoantigens in paraneoplastic syn-dromes.References1 Graus F, Cordon-Cardo C, Posner JB: Neuronal antinuclear antibody insensory neuronopathy from lung cancer. Neurology 1985;35:538–543.2 Dropcho EJ: Antiamphiphysin antibodies with small-cell lung carcinomaand paraneoplastic encephalomyelitis. Ann Neurol 1996;39:659–667.3 Voltz R, Gultekin SH, Rosenfeld MR, Gerstner E, Eichen J, Posner JB,Dalmau J: A serologic marker of paraneoplastic limbic and brain-stemencephalitis in patients with testicular cancer. N Engl J Med 1999;340:1788–1795.4 Honnorat J, Aguera M, Zalc B, Goujet C, Quach T, Antoine JC, Belin MF:POP66, a paraneoplastic encephalomyelitis-related antigen, is a marker ofadult oligodendrocytes. J Neuropathol Exp Neurol 1998;57:311–322.5 Kaneko K, Nakamura A, Yoshida K, Kametani F, Higuchi K, Ikeda S:Glial fibrillary acidic protein is greatly modified by oxidative stress in ace-ruloplasminemia brain. Free Radic Res 2002;36:303–306.6 Marangos PJ, Schmechel D, Zis AP, Goodwin FK: The existence and neu-robiological significance of neuronal and glial forms of the glycolyticenzyme enolase. Biol Psychiatry 1979;14:563–579.7 Banga JP, McGregor AM: Enzymes as targets for autoantibodies in humanautoimmune disease: Relevance to pathogenesis? Autoimmunity 1991;9:177–182.8 Coppel RL, McNeilage LJ, Surh CD, Van de Water J, Spithill TW, Whit-tingham S, Gershwin ME: Primary structure of the human M2 mitochon-drial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyl-transferase. Proc Natl Acad Sci USA 1988;85:7317–7321.9 Adamus G, Aptsiauri N, Guy J, Heckenlively J, Flannery J, Hargrave PA:The occurrence of serum autoantibodies against enolase in cancer-associat-ed retinopathy. Clin Immunol Immunopathol 1996;78:120–129.10 Ochi H, Horiuchi I, Araki N, Toda T, Araki T, Sato K, Murai H, OsoegawaM, Yamada T, Okamura K, Ogino T, Mizumoto K, Yamashita H, Saya H,Kira J: Proteomic analysis of human brain identifies alpha-enolase as anovel autoantigen in Hashimoto’s encephalopathy. FEBS Lett 2002;528:197–202.11 Graus F, Keime-Guibert F, Rene R, Benyahia B, Ribalta T, Ascaso C,Escaramis G, Delattre JY: Anti-Hu-associated paraneoplastic encephalo-myelitis: Analysis of 200 patients. Brain 2001;124:1138–1148.Takahiko Tokuda, Third Department of Internal MedicineShinshu University School of Medicine3-1-1 Asahi, Matsumoto 390-8621 (Japan)Tel. +81 263 372673, Fax +81 263 340929E-Mail ttokuda@gipac.shinshu-u.ac.jpEur Neurol 2004;51:233–235DOI: 10.1159/000078548Bilateral Anterior Inferior Cerebellar ArteryTerritory Brachium pontis Infarcts of ProbableHemodynamic CauseRoger Kalla a, Thomas Mayer b, Gerhard F. Hamann aDepartments of a Neurology and b Neuroradiology,Ludwig Maximilian University, Klinikum Grosshadern,Munich, GermanyIntroductionInfarcts in the territory of the anterior inferior cerebellar artery(AICA) are rare [1–3]. The clinical signs first described by Adams [4]in 1943 in a patient who experienced rotational vertigo, vomiting,tinnitus and dysarthria are dominated by brain stem signs. This isdue to the fact that the AICA supplies the middle and lower third ofthe lateral pontine region and the anterolateral parts of the cerebel-lum with the middle cerebellar peduncle, the flocculus and the anteri-or part of the cerebellar lobules [2]. We present the case of a 51-year-old man with a symmetrical infarct in the bilateral middle cerebellarpeduncles and the left flocculus. The occlusion of both vertebral234 Short ReportsFig. 1. A, B Cranial magnetic resonance imaging revealed bilateral middle cerebellar peduncular infarctions(A, arrows, diffusion-weighted MRI, b = 1,000; B, arrows, T2 MRI) and an infarction in the flocculus on the left side.All infarcts were confined to the territory of the anterior inferior cerebellar arteries. C–E Vertebral angiographyshowed occlusion of the right and left vertebral arteries (C, arrowheads) and collateralization of both vertebral arter-ies (D, E, arrows).Short Reports 235arteries suggested a hemodynamic mechanism involving hypoperfu-sion and subsequent infarction in the middle cerebellar peduncles.Case ReportThe patient was admitted to our hospital after 3 days of progres-sive gait and postural imbalance, dizziness, numbness of the left sideof the face and dysarthria. Three months before admission, he hadhad recurrent episodes of rotatory vertigo and visual disturbanceslasting several seconds. He also had vascular risk factors, hyperten-sion, peripheral arteriosclerosis and had smoked for 20 years. Thepatient history documented an infarct of the right middle cerebralartery territory 7 years before which caused no neurological deficits.The MRI revealed microangiopathy, but no territorial infarct. Neu-rological examination at admission showed a conscious and orientedpatient with bilateral horizontal gaze nystagmus, ocular tilt reactionto the left, numbness of the left side of the face, slight right-sidedfacial weakness, dysarthria, ataxia in all four limbs and axial latero-pulsion to both sides, which made it impossible for him to stand.Muscle strength, deep tendon reflexes and sensations were all nor-mal. Babinski’s sign was not present. An electrocardiogram was nor-mal, and a transthoracic and transesophageal echocardiogram re-vealed a moderately dilated left atrium without thrombi. The MRIwith fast echoplanar diffusion-weighted images (1.5 T, Siemens,Vision) showed marked hyperintensity signals (fig. 1A, arrows) bilat-erally in the middle cerebellar peduncles on the left more than on theright side and in the left flocculus as a cause of the symptoms. Otherareas in the brain stem or cerebellum were not involved. Blood chem-istry including homocysteine and screening for thrombophilic riskfactors was normal. The Doppler sonography and transcranialDoppler sonography revealed a 50% stenosis of the arteria carotisinterna and bilateral low flow in the vertebral arteries. Digital sub-traction arteriography via a transfemoral approach disclosed extra-cranial occlusion of the left vertebral artery at the level of C1 (fig. 1C,arrowheads) and a 50–60% stenosis at the origin of the vertebralartery. The intradural segment of the left vertebral artery was collat-eralized by the arteria spinalis anterior (fig. 1D, arrowhead). Theright vertebral artery was occluded at the exit from the subclavianartery (fig. 1C) and had a collateralization through muscle branchesat the level of C2 (fig. 1E). The top of the basilar artery up to the issueof the superior cerebellar artery was supplied by the right internalcarotid artery via the posterior communicating artery on the sameside. The left posterior cerebral artery was filled by a leptomeningealanastomosis, and the left carotid artery showed an arterioscleroticnarrowing in the pars petrosa. The AICAs and superior cerebellararteries could be clearly visualized. Under the misconception that theocclusion of the left vertebral artery was relatively fresh, we treatedthe patient with 24-hour infusion therapy with Aggrastat, whichmight have led to a recanalization of the left vertebral artery. How-ever, the unchanged findings on angiographic reexamination the nextday prompted us to administer heparin intravenously. The patientimproved under stroke unit treatment over the next days. He becameable to sit independently, the limb ataxia lessened and there were nomore attacks of vertigo during mobilization. However, the pro-nounced dysarthria remained. Long-term secondary stroke pre-vention was achieved by oral anticoagulation.DiscussionCranial MRI demonstrated bilateral cerebellar infarction of themiddle cerebellar peduncles in our patient. The middle cerebellarpeduncle, the flocculus and the anterior part of the cerebellar lobules[2] are mainly supplied by the AICA. Acute infarcts in the territory ofthe AICA are rare, having a frequency of 0.5% of all acute strokes.They account for 5.2% of infarcts affecting the vertebrobasilar terri-tory [5].The complete AICA syndrome first described by Adams [4] in asingle patient with vertigo, vomiting, trigeminal sensory loss, Hor-ner’s syndrome, peripheral facial palsy, ipsilateral hearing loss withtinnitus, dysmetria of the limbs, dysarthria and contralateral temper-ature and sensory loss sparing the face is rare [2]. The usual clinicalmanifestation is a crossed brain stem syndrome. Only three cases ofinfarcts in the territory of the AICAs and restricted to the bilateralterritory of the middle cerebellar peduncles have been reported [1, 6,7]. In our case, the vertebral angiography revealed extracranial occlu-sion of the left vertebral artery at the level of C1 and occlusion of theright vertebral artery at its exit from the subclavian artery; however,the AICAs were clearly visualized. This suggests that a hemodynamicmechanism with bilateral, focally lowered blood flow in the areasmainly supplied by the AICA subsequently led to an infarction in themiddle cerebellar peduncles. These areas might be the most vulnera-ble parts of the territory affected by ischemia of the AICA [2], andthus other areas supplied by the AICA were not involved. The verte-brobasilar occlusion in our patient might have been caused by anatherothrombotic mechanism at the site of an underlying stenosis inthese vessels. An atherosclerotic etiology is considered the most fre-quent cause of AICA infarcts. [3, 5]AcknowledgementWe thank Ms. J. Benson for copyediting the manuscript.References1 Akiyama Y, Takizawa S, Takuoka K, Ohnuki Y, Kobayashi N, ShinoharaY: Bilateral middle cerebellar peduncle infarction caused by traumatic ver-tebral artery dissection. Neurology 2001;56:693–694.2 Amarenco P, Hauw JJ: Cerebellar infarction in the territory of the anteriorand inferior cerebellar artery: A clinicopathological study of 20 cases. Brain1990;113:139–155. 3 Amarenco P, Rosengart A, DeWitt LD, Pessin MS, Caplan LR: Anteriorinferior cerebellar artery territory infarcts. Mechanisms and clinical fea-tures. Arch Neurol 1993;50:154–161.4 Adams RD: Occlusion of anterior inferior cerebellar artery. Arch NeurolPsychiatry 1943;49:765–770.5 Roquer J, Lorenzo JL, Pou A: The anterior inferior cerebral artery infarcts:A clinical-magnetic resonance imaging study. Acta Neurol Scand 1998;97:225–230.6 Sato K: Bilateral middle cerebellar peduncle infarction (in Japanese). NoTo Shinkei 1998;50:1036–1037.7 Tsukamoto T, Seki H, Saitoh J, Watanabe K: A case of bilateral cerebellarpeduncle infarction. Jpn J Med 1991;30:376–378.Gerhard F. Hamann, MD, Department of NeurologyKlinikum Grosshadern, Marchioninistrasse 15DE–81377 Munich (Germany)Tel. +49 89 7095 3670, Fax +49 89 7095 3677E-Mail hamann@brain.nefo.med.uni-muenchen.de

A case of bilateral cerebellar peduncle infarction.

A: The anterior inferior cerebral artery infarcts: A clinical-magnetic resonance imaging study.

Bilateral middle cerebellar peduncle infarction (in Japanese). No To Shinkei

Caplan LR: Anterior inferior cerebellar artery territory infarcts. Mechanisms and clinical features.

Hauw JJ: Cerebellar infarction in the territory of the anterior and inferior cerebellar artery: A clinicopathological study of 20 cases.

Occlusion of anterior inferior cerebellar artery.

Shinohara Y: Bilateral middle cerebellar peduncle infarction caused by traumatic vertebral artery dissection.

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Bilateral anterior inferior cerebellar artery territory brachium pontis infarcts of probable hemodynamic cause

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