References 1 Hart RG, Easton JD: Dissections. Stroke 1985;16:925–927. 2 Caplan LR, Zarins CK, Hemmati M: Spontaneous dissection of the exracranial vertebral arteries. Stroke 1985;16:1030–1038. 3 Bartels E, Flugel KA: Evaluation of extracranial vertebral artery dissection with duplex color-flow imaging. Stroke 1996;27:290–295. 4 Auer A, Felber S, Schmidauer C, Waldenberger P, Aichner F: Magnetic resonance angiographic and clinical features of extracranial vertebral artery dissection. J Neurol Neurosurg Psychiatry 1998;64:474–481. 5 Schievink WI, Mokri B, O’Fallon WM: Recurrent spontaneous cervicalartery dissection. N Engl J Med 1994;330:393–397. 6 Leys D, Moulin T, Stoijkovic T, Begey S, Chavot D: Follow-up of patients with history of cervical artery dissection. Cerebrovasc Dis 1995; 5: 43– 49. 7 Touze E, Gauvrit JY: Natural history of cervical arterial dissection: Review of the literature and preliminary results from a national study group. J Neuroradiol 2002;29:251–256. 8 Touze E, Gauvrit JY, Moulin T, Meder JF, Bracard S, Mas JL: Risk of stroke and recurrent dissection after cervical artery dissection: A multicenter study. Neurology 2003;61:1347–1351. 9 Bogousslavsky J, Despland PA, Regli F: Spontaneous carotid dissection with acute stroke. Arch Neurol 1997;44:137–140. 10 Atkinson JL, Piepgras DG, Huston J 3rd, Mokri B: Cervical artery dissections: Evidence for redissection in previously dissected arteries: Report of three cases. Neurosurgery 2002;51:797–801. 11 Goldstein LB, Gray I, Hulette CM: Stroke due to recurrent ipsilateral carotid artery dissection in a young adult. Stroke 1995; 26:480–483. 12 Earnest F, Forbes G, Sandok BA, Piepgras DG, Faust RJ, Ilstrup DM, Arnalt LJ: Complication of cerebral angiography: Prospective assessment of risk. AJR Am J Roentgenol 1984;142:247–253. 13 Touboul PJ, Mas JL, Bausser MG, Laplane D: Duplex scanning in extracranial vertebral artery dissection. Stroke 1988;19:116–121. 14 De Bray JM, Penisson-Besnier I, Dubas F, Emile J: Extracranial and intracranial vertebrobasilar dissections: Diagnosis and prognosis. J Neurol Neurosurg Psychiatry 1997;63:46–51. Eva Morandi, MD, Neurology Clinic, Ospedale di Montichiari Via Ciotti, 154, IT–25018 Montichiari, Brescia (Italy) Tel. +39 030 9963271, Fax +39 030 9963705 E-Mail evamorandi@yahoo.it 410 Cerebrovasc Dis 2005;19:410–414 DOI: 10.1159/000086104 Amnestic Syndrome of the Subcallosal Artery: A Novel Infarct Syndrome Michael Moussouttas, Joseph Giacino, Nikolaos Papamitsakis New Jersey Neuroscience Institute, JFK Medical Center, Seton Hall University, Edison, N.J., USA Introduction Cerebrovascular causes of amnesia have been described with thalamic, medial temporal, basal frontal, posterior cingular, and internal capsule lesions [1]. Two cases of isolated anterograde amnesia resulting from bilateral anterior fornix infarction (BAFI) have been described [1, 2]. Herein we present a third such case, and identify a novel arterial syndrome. Additionally, we provide the most extensive evaluation into the putative mechanisms of ischemia, with detailed neuropsychological testing and the only correlative functional PET imaging reported. Case Report A 61-year-old right-handed male was admitted to the hospital after awakening with ‘confusion’. His medical history was notable for hypertension, hyperlipidemia, and coronary artery disease. Neurological examination revealed only severe anterograde amnesia with complete inability to recall three words after several minutes. No affective or behavioral deficits were noted, and serial reexaminations consistently reproduced the impairment in word recall. An acute myocardial infarction was diagnosed based on EKG T-wave changes and serum troponin level elevations. Serum folate and cobalamin levels, TSH, VDRL, Lyme titers, and cryptococcal antigen levels were all normal. Cerebrospinal fluid analysis was negative. Cerebral MRI revealed acute infarctions in the anterior forniceal columns bilaterally (measuring approximately 1.7 cm), in the genu of the corpus callosum, the septum pellucidum, and in a punctate area of the left frontal subcortical region (fig. 1). Cerebral and cervical MRA studies revealed hypoplasia of the left A1 anterior cerebral artery segment (fig. 2), 30% stenosis of the contralateral internal carotid artery origin, and minor stenoses of the vertebral artery orifices. Routine echocardiography and ambulatory cardiac monitoring studies were unrevealing, but transesophageal echocardiography demonstrated left atrial spontaneous echo contrast. Cerebral PET imaging performed 1 month later demonstrated moderately decreased metabolic activity in the left thalamus and temporal lobe, and mildly decreased metabolism in the left frontal and parietal regions. Neuropsychological assessment performed 5 months after the event demonstrated poor acquisition of novel verbal material, with severely impaired recall of both verbal and visual information (table 1). In contrast, performance was normal on yes/no and two-alternative forced-choice recognition measures. Processing speed, mental control, and executive functions were also affected but to a lesser and more variable degree. Visuospatial functions were well preserved. During the entire period of investigation, from onset of symptoms to time of PET scan to the point when neuropsychological testing was performed, the patient remained Case Reports Downloaded by: Fudan University Library 61.129.42.15 - 5/4/2015 1:59:07 PM They indicate the presence of an abnormal structure either in the arterial lumen or in the vessel wall. In our patient, we were unable to observe ultrasound abnormalities at the first examination even if the clinical signs were suspicious. Only after 8 days from the beginning of the pain was ultrasound diagnostic for vertebral dissection. This can be tentatively explained by the fact that the initial dissection was of too limited an extent to produce any significant changes in the flow pattern and the location too distal to be directly imaged with ultrasound. Vertebral artery dissection may not be detected by ultrasound as long as the intramural hematoma remains of a size insufficient to interfere with the blood flow in the true lumen. Therefore, in cases where the index of suspicion is high, a repeat ultrasound examination is mandatory if MRA is not readily available. 1 Fig. 1. MRI diffusion images obtained at the time of symptom onset, demonstrating acute ischemia of the bilateral anterior fornices (A), septum pellucidum and genu of the corpus callosum (B), and left frontal subcortical region (C). MRI FLAIR imaging performed 10 days later, demonstrating corresponding residual infarcted areas (D– F). Fig. 2. MRA (oblique view) of the intracranial vessels, demonstrating aplasia of the left A1 segment and common contralateral origin of the anterior cerebral arteries. 411 Downloaded by: Fudan University Library 61.129.42.15 - 5/4/2015 1:59:07 PM Case Reports 2 clinically stable and unchanged with persistent profound deficits in recall memory. Raw score AgePercenadjusted tile scaled score Reference range 13 84 high normal Attention Digit span (RBANS) Forward 5 Backward 4 Mental control (WMS-III) 11/40 4 Letter/number sequence (WMS-III) 10 Trail making test: part A 64s 4 18 36 2 50 3 normal normal impaired normal low normal 16 normal 4 1 low normal impaired <1 impaired General ability Information (WAIS-III) Processing speed Digit symbol Stroop interference test Word Color Memory Acquisition (RBANS) Immediate memory index List learning Story memory Retrieval List recall (RBANS) Story recall (RBANS) Figure recall (RBANS) Benton visual retention test Correct Errors Recognition List recognition (RBANS) Warrington word recognition Warrington face recognition Spatial/constructional Visuospatial index (RBANS) Line orientation Figure copy Block design (WAIS-III) Matrix reasoning (WAIS-III) Complex figure test Clock drawing Time setting Executive processes Similarities (WAIS-III) Trail making test: part B Stroop interference Semantic fluency Wisconsin card sorting task Categories completed Total errors Perseverative responses Trials to complete 1st cat. Emotional control Behavioral control 7 80 51 61 18/40 9/24 1/10 3/12 8/20 impaired impaired borderline 5/10 8 6 1 low normal impaired 19/20 48/50 38/50 87 16 normal high normal normal 39 normal 7 9 16 37 53 normal normal normal normal normal 9 5 37 5 62 normal low normal normal low normal 11–16 16 21 6–10 low normal normal normal low normal normal normal 96 15/20 19/20 30.5/36 161s 14 2 24 11 35 Reference ranges were established by converting raw scores and age-adjusted scaled scores to percentiles according to the following parameters: 685 (high normal), 16–84 (normal), 3–15 (low normal), ^2 (impaired). When norms were not available for converting raw scores to percentiles, cutoff scores were used as indicated in the appropriate test manual. RBANS = Repeatable Battery for the Assessment of Neuropsychological Status; WAIS = Wechsler Adult Intelligence Scale; WMS = Wechsler Memory Scale. 412 Discussion The vascular supply to the anterior fornices emanates from any one or two of the three midline posterior perforating arterioles originating from the anterior communicating artery [3]. Of these vessels, the hypothalamic artery provides no septal or callosal supply, whereas the median callosal artery supplies the body and splenium of the corpus callosum. In addition to supplying the anterior fornices, the subcallosal artery supplies the septum pellucidum and anterior portion of the cingulate gyrus, and is the major contributor to the rostrum and genu of the corpus callosum (fig. 3). In all reported cases of BAFI, the septum pellucidum and genu of the corpus callosum have invariably been involved, and in one instance the lesion extended to include the anterior cingulate gyrus. Consistent with the arterial distribution of the subcallosal artery, cerebral imaging studies in patients with BAFI have uniformly demonstrated lobular and possibly even noncontiguous areas of ischemia, with total maximum diameters exceeding the upper limit for lacunes. Analogous bilateral thalamic infarctions with separate foci of ischemia and cumulative diameters greater than 1.5 cm have been variably attributed to microvascular, large vessel, and cardiogenic processes [4]. Occlusions of arterioles similar in caliber to that of the subcallosal artery have also been ascribed to various mechanisms [5]. However, anatomical features of the perforators supplying the corpus callosum have been shown to impart a unique resistance to microvascular disease [6]. Conversely, arterioembolic and cardioembolic processes have accounted for the great majority of infarctions in the anterior cerebral vessels, particularly in the presence of a hypoplastic A1 segment [7]. In one of the prior case reports of BAFI, a microvascular mechanism was proposed, but no formal assessment of cardiac rhythm or of the intracranial vessels was made, and therefore alternative mechanisms of ischemia were not entirely excluded [2]. In the case report by Park et al. [1], cardiac ultrasound imaging was not performed and no mention was made of the cervical vessels. No mechanism of infarction was proposed in that case. In our patient, a microvascular process was excluded based on the distant foci of ischemia, and arterioembolization appeared unlikely in view of the absence of major arterial stenoses. Given that cerebral infarctions are known to complicate 2–4% of acute myocardial infarctions [8], and since spontaneous echo contrast has been identified as a risk factor for cerebral ischemia [8], cardioembolization was suspected as the cause in our case. Neuropsychological testing in our patient revealed a clear dissociation in episodic memory functions, with severely compromised retrieval abilities demonstrated on four different verbal and visual measures of free recall, and uniformly preserved familiarity as evidenced by accurate identification of words and figures on forced-choice and yes/no paradigms. On tests requiring acquisition of stories and word lists, learning and recall scores were markedly impaired, whereas performance on recognition tests was consistently within normal limits. These findings suggested sufficient stimulus encoding to enable accurate discrimination of target from nontarget items, yet a diminished learning capacity with deficient spontaneous recall. A similar discrepancy between recall and recognition memory functions was observed in the case by Park et al. [1]. Case Reports Downloaded by: Fudan University Library 61.129.42.15 - 5/4/2015 1:59:07 PM Table 1. Neuropsychological test results Fig. 3. Arterial vasculature of the midline cerebral structures. Depicted is the subcallosal arterial (sa) supply, with proximal branches to the fornix (3) and inferior septum, and distal branches to the anterior septum and genu of the corpus callosum. Reproduced with permission [3]. Case Reports tures. The low activity seen in the left frontal and parietal areas may also have represented diaschisis, in this instance between ipsilateral cortical and subcortical memory circuits. These findings raise the possibility that the observed memory deficits may have in part resulted from hippocampal hypoactivity, and not simply memory pathway interruption. Frontal hypometabolism may also have contributed to the memory deficits, as well as to the difficulties in attention and executive functions. In contrast to the lesions of the fornix and septum, it is unlikely that the punctate subcortical lesion or the lesion in the genu of the corpus callosum accounted for the dense amnesia observed, or for the diffuse functional metabolic abnormalities. Previous functional studies have revealed decreased metabolism and perfusion in the ipsilateral cortical, lobar, and limbic regions of patients with infarctions of the thalamus and thalamic projections within the genu of the internal capsule [14, 15]. Since thalamic amnesia has been hypothesized to represent a disconnection syndrome resulting from damage to the internuclear fiber tracts (internal lamina) [16], lesions of afferent memory tracts projecting to the thalamus, such as the fornix via the mammillary bodies, may be expected to produce similar findings on functional imaging. During the time interval between PET imaging and neuropsychological testing, no clinically evident change or improvement in recall memory was observed. Since PET data were not available at the time of neuropsychological testing, the underlying mechanism of amnesia is unclear. PET imaging simultaneous to neuropsychological testing may have elucidated the mechanism of amnesia if diaschisis were no longer apparent, implicating pathway interruption as the cause. Conversely, if diaschisis had again been present, functional disconnection or pathway interruption may have been equally plausible explanations. In view of the information available, either mechanism may be responsible for the observed memory deficits. In conclusion, isolated amnesia characterized by profound deficits in memory retrieval may be caused by bilateral infarctions of 413 Downloaded by: Fudan University Library 61.129.42.15 - 5/4/2015 1:59:07 PM In a recently proposed model of memory processing, Aggleton and Brown [9] introduced the concept of parallel circuits for episodic recall versus familiarity-based memory functions. Based on this model, the fornix forms an integral part of the hippocampalanterior thalamic pathway mediating memory retrieval, whereas a separate perirhinal-medial thalamic system mediates item familiarity. Accordingly, these authors postulate that lesions of the fornix may selectively impair recall processes, and provide corroborating evidence from experimental animal studies and human case reports. The memory profile obtained in our patient supports this premise, and advances the concept of parallel memory circuits. Based on clinical, experimental and anatomical observations, the septal nuclei have been implicated in memory, affective, and behavioral functions. As a major source of cholinergic input to the hippocampus, the septal nuclei possess extensive afferent and efferent projections to and from the hippocampal formation [10]. However, in case reports of amnesia resulting from septal lesions, the memory deficits have usually been ascribed to forniceal involvement [11, 12], and in the only case of isolated amnesia attributed to septal nuclear damage, concurrent involvement of the fornix was impossible to definitively exclude [13]. Selective septal lesions have also been found to cause hyperreactivity, rage, and hypersexuality [10]. In the reported cases of BAFI, involvement of the septal nuclei cannot be entirely excluded as having contributed to the observed memory deficits. However, the absence of affective and behavioral symptoms, the lack of data definitively linking septal nuclear lesions to memory loss, and the preponderance of data supporting a prominent role for the fornix in memory function suggest a lesser role for the nuclei of the septum. PET imaging in our case provided a view of the distant functional effects of anterior fornix and septal nuclear infarction. Given the absence of thalamic and temporal lobe lesions on MRI, the moderately decreased metabolic activity in these regions was presumably the result of a functional disconnection due to interruption of reciprocal projections to and from the infarcted limbic struc- References 1 Park S, Hahn J, Kim J, Na D, Huh K: Memory deficits after bilateral anterior fornix infarction. Neurology 2000;54:1379–1382. 2 Moudgil S, Azzouz M, Al-Azzaz A, Haut M, Gutmann L: Amnesia due to fornix infarction. Stroke 2000;31:1418–1419. 3 Ture U, Yasargil G, Krisht A: The arteries of the corpus callosum – A microsurgical anatomic study. Neurosurgery 1996;39:1075–1084. 4 Kumral E, Evyapan D, Balkir K, Kutluhan S: Bilateral thalamic infarction – Clinical, etiological, and MRI correlates. Acta Neurol Scand 2001;103: 35–42. 5 Leys D, Mounier-Vehier F, Lavenu I, Rondepierre P, Pruvo J: Anterior choroidal artery territory infarcts. Study of presumed mechanisms. Stroke 1994;25:837–842. 6 Moody D, Bell M, Challa V: The corpus callosum, a unique white matter tract: Anatomic features that may explain sparing in Binswanger disease and resistance to flow of fluid masses. AJNR Am J Neuroradiol 1988; 9: 1051–1059. 7 Kazui S, Sawada T, Naritomi H, Kuriyama Y, Yamaguchi T: Angiographic evaluation of brain infarction limited to the anterior cerebral artery territory. Stroke 1993;24:549–553. 414 8 Brickner M: Cardioembolic stroke. Am J Med 1996;100:465–474. 9 Aggleton J, Brown M: Episodic memory, amnesia, and the hippocampalanterior thalamic axis. Behav Brain Sci 1999;22:425–444. 10 Cavazos J, Wang C, Sitoh Y, Ng S, Tien R: Anatomy and pathology of the septal region. Neuroimaging Clin N Am 1997;7:67–78. 11 Gil Neciga E, Gil Peralta A, Polaina M, Sureda B, Bautista J: Cyst of the septum pellucidum and Korsakoff’s psychosis. Eur Neurol 1989; 29: 99– 101. 12 Sato K, Nagayama T, Fujimura M, Okamoto K, Kamiya M, Nakazato Y: A case of germinoma in the septum pellucidum manifesting as amnesia and hemiparesis. Acta Neurochir (Wien) 2003;145:923–926. 13 Berti A, Arienta C, Papagno C: A case of amnesia after excision of the septum pellucidum. J Neurol Neurosurg Psychiatry 1990;53:922–924. 14 Clarke S, Assal G, Bogousslavsky J, Regli F, Townsend D, Leenders K, Blecic S: Pure amnesia after unilateral left polar thalamic infarct – Topographic and sequential neuropsychological and metabolic (PET) correlations. J Neurol Neurosurg Psychiatry 1994;57:27–34. 15 Tatemichi T, Desmond D, Prohovnik I: Strategic infarcts in vascular dementia. A clinical and brain imaging experience. Arzneimittelforschung 1995;45:371–385. 16 Schmahmann J: Vascular syndromes of the thalamus. Stroke 2003; 34: 2264–2278. Michael Moussouttas, MD, Neuroscience Institute JFK Medical Center, 65 James Street, Edison, NJ 08818 (USA) Tel. +1 732 321 7000, ext. 61164, Fax +1 732 632 1671 E-Mail arista1@pol.net Case Reports Downloaded by: Fudan University Library 61.129.42.15 - 5/4/2015 1:59:07 PM the anterior fornices (and septal nuclei), and may result from various mechanisms including cardioembolization. Involvement of the subcallosal artery may be causative. The term ‘amnestic syndrome of the subcallosal artery’ may be appropriate in describing this rare vascular syndrome.