Agenesis of the Arcuate Fasciculi in Congenital Bilateral Perisylvian Syndrome a Diffusion Tensor Imaging and Tractography Study

OBSERVATION Agenesis of the Arcuate Fasciculi in Congenital Bilateral Perisylvian Syndrome A Diffusion Tensor Imaging and Tractography Study

Byron Bernal, MD; Gustavo Rey, PhD; Catalina Dunoyer, MD; Harshad Shanbhag, MS; Nolan Altman, MD

Objective: To describe the absence of the arcuate fas- Main Outcome Measures: Neuropsychology evalu- ciculi in 2 cases of congenital bilateral perisylvian syn- ation; fractional anisotropy, apparent diffusion coeffi- drome (CBPS). cients, and anatomical aspect of the tracts.

Design: Case series. Results: Absence of the arcuate fasciculus was observed in both subjects. Ancillary findings were com- Setting: Pediatric referral hospital–based study. plete absence of the superior longitudinal fasciculi in 1 case and underdevelopment in the other. Low fractional Patients: Two patients with CBPS, referred to our anisotropy of the left inferior occipitofrontal fasciculus institution as candidates for surgical treatment of was found in both cases. The same tract was malori- epilepsy. ented in 1 of the cases.

Intervention: Diffusion tensor imaging (1.5-T scan- Conclusion: Agenesis of the arcuate fasciculus may ac- ner; 15 encoding directions; b=800 s/mm2) and deter- company CBPS. ministic tractography of the main projection and association tracts. Arch Neurol. 2010;67(4):501-505

HE CONGENITAL BILATERAL speech deficit may contribute to the perisylvian syndrome understanding of the arcuate fasciculus (CBPS) is a type of corti- function. cal developmental abnor- mality characterized by poorT operculation of the parietal and REPORT OF CASES frontal lobes, wide lateral sulcus, polymicrogyria, orofacial diplegia, epilepsy, and The clinical and neuroradiological find- developmental delay.1,2 Seizures are pres- ings of 2 cases with CBPS are summa- ent in 65% of cases.3,4 To our knowledge, rized in the Table. Case 2 has no arcuate CBPS has not been studied to date with fasciculus but has the remnant fibers of diffusion tensor imaging and fiber trac- the superior longitudinal fasciculus. tography. Normally, the superior longitudinal fas- We describe 2 cases with absence of ciculus has, in addition to the arcuate the arcuate fasciculus (as part of agenesis fasciculus, a bundle of short fibers con- or hypoplasia of the superior longitudi- necting the parietal areas (supramarginal nal fasciculus) in CBPS using diffusion gyrus) with frontal areas. In addition, the tensor imaging and fiber tractography in fractional anisotropy of the left inferior relation to clinical and neuropsychologi- occipitofrontal fasciculus was found to Author Affiliations: Miami Children’s Hospital (Drs Bernal, cal findings. To our knowledge, there are be low in both cases and bilaterally in Rey, Dunoyer, and Altman and no existing reports describing bilateral the cingulum of case 2. Mr Shanbhag) and MCH Brain agenesis of the arcuate fasciculus in this A single-shot, spin-echo, echo-planar Institute (Drs Bernal, Rey, and condition. The correlation of this finding imaging sequence with diffusion weighting Dunoyer), Miami, Florida. with the clinical analysis of the language/ consisting of 15 encoding directions was

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Case 1 Case 2 Age, y 13 18 Sex F M Handedness Right Right Main diagnosis Intractable epilepsy; CBPS Intractable epilepsy; CBPS Onset of seizures, y 3 12 Type of seizure Right side head and eye version Right side head version, staring, jaw movements General developmental Motor: normal; poor attention; deficit executive functions Motor: normal, but with sucking and swallowing milestones problems as infant Language developmental Speech severely delayed; poor language comprehension Speech severely delayed; poor language comprehension milestones Neuropsychology evaluation Overall intellectual functioning Moderate to severe impaired range (IQ=41; VCI Mildly impaired (IQ=64; VCI score=82; POI score=67)b score=55; PRI score=49; WMI score=50; PSI score=50)a Language Prosody Poor Poor Articulatory skills Poor Poor Conduit d’approachec None None (not described) Automatic series Normal Normal Automatic series backward Normal Unable Phonemic fluency Severely impaired (standard score Ͻ40)d Moderately impaired (standard score=52) Semantic fluency Borderline (standard score=71) Moderately impaired (standard score=54) Verbal memory Poor, with relatively preserved delayed recall Borderline (scale score=5)e; good delayed recall (scale score=6)e Verbal reasoning Severely impaired (scale score=3)a Borderline (scale score=6)b Nonverbal reasoning Severely impaired (scale score=1)a Impaired (scale score=4)b Constructional praxis Poor (VMI standard score=61; scale score=1)a Borderline (scale score=5)f; very poor graphomotor skills (VMI standard score=45) Auditory working memory Severely impaired (digit span, scale score=1)a Impaired (digit span, scale score=3)b Memory for faces Borderline (scale score=6)g; normal delayed recall (scale Moderately impaired (raw score=7)g; better for delayed score=9)g recall (raw score=10)g Visual psychomotor speed Severely impaired (PSI standard score Ͻ40) Impaired (PSI standard score=57) Fine motor dexterity Severely impaired bilaterally: RH standard score Ͻ40; Severely impaired: RH standard score Ͻ40; LH standard LH standard score=unable to performh score Յ40h Neuropsychological global “Diffuse cerebral dysfunction, with relatively preserved “Multiple cognitive domains impairment with a trend of profile performance on measures associated with greater dysfunction of the nondominant hemisphere mesiotemporal systems” [with] preserved mesiotemporal regions” EEG Interictal: right frontotemporal slowing; ictal: bilateral Interictal: bilateral temporal spikes and right temporal central epileptiform activity slow waves; ictal: bilateral centrotemporal sharp slow waves more prominent in the right side MRI Bilateral opercular cortical malformation; thick cortex, Bilaterally poorly formed operculum; cortical thickening, small gyri, abnormal sulcation (Figure 1A); left polymicrogyria in opercular and hippocampal regions cerebellum hypoplasia (Figure 1B); left cerebellar aplasia DTI/tractography Color-coded FA map: failure to demonstrate the SLF Color-coded FA map: small and poorly defined SLFs bilaterally (Figure 4); bilateral abnormal IOFF (Figure 5); fiber tractography: absence of the arcuate orientation (curved upward); lack of cerebellar fibers fibers (Figure 6) Other associative tracts (FA/ADC) Left IOFF: 0.33i/0.88 Left IOFF: 0.38i/0.85 Right IOFF: 0.53/0.81 Right IOFF: 0.46/0.86 Left ILF and IOFF: 0.48/0.84 Left ILF and IOFF: 0.47/0.94 Right ILF and IOFF: 0.47/0.89 Right ILF and IOFF: 0.52/0.90 Left cingulum: 0.44/0.76 Left cingulum: 0.39i/0.82 Right cingulum: 0.40/0.80 Right cingulum: 0.35i/0.81 Left internal capsule: 0.61/0.80 Left internal capsule: 0.53/0.78 Right internal capsule: 0.55/0.82 Right internal capsule: 0.51/0.82

Abbreviations: ADC, apparent diffusion coefficients; CBPS, congenital bilateral perisylvian syndrome; DTI, diffusion tensor imaging; EEG, electroencephalography; FA, fractional anisotropy; IOFF, inferior occipitofrontal fasciculus; ILF, inferior longitudinal fasciculus; LH, left hand; MRI, magnetic resonance imaging; POI, Perceptual Organization Index; PRI, Perceptual Reasoning Index; PSI, Processing Speed Index; RH, right hand; SLF, superior longitudinal fasciculus; VCI, Verbal Comprehension Index; VMI, Beery-Buktenica Developmental Test of Visual-Motor Integration; WMI, Working Memory Index. a Wechsler Intelligence Scale for Children–Fourth Edition Spanish Version. b Wechsler Adult Intelligence Scale–Third Edition Full-Scale IQ. c Conscious effort to correct mispronunciations. d Multilingual Aphasia Examination Spanish Version. e Wide Range Assessment of Memory and Learning, Second Edition. f Wechsler Adult Intelligence Scale–Third Edition Block Design. g NEPSY Memory for Faces subtest. h Grooved Pegboard Test. i Values lower than normal range accordingly with in-house standardization.

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P Figure 1. T1-weighted axial magnetic resonance images showing main findings of congenital bilateral perisylvian syndrome. A, Case 1. B, Case 2. Notice the distinctive widening of the sylvian fissure with “exposure” of the insula to the cortical surface and abnormal sulcation.

Figure 3. Normal appearance of the superior longitudinal fasciculi and the arcuate fasciculi in a normal volunteer. The superior longitudinal fasciculi (double thin arrows), conformed by parietal fibers (arrowheads), and the arcuate fasciculi (long single arrows). The superior longitudinal fasciculi on the right side does not carry arcuate fibers. Red indicates left side; Figure 2. Normal appearance of the superior longitudinal fasciculus (arrows) yellow, right side; A, anterior; P, posterior. in a normal volunteer defined at this level as triangular green shapes lateral to the blue descending fibers of the corticospinal tract. COMMENT performed in a 1.5-T scanner (Figure 1). A diffusion weighting (b) of 800 s/mm2 was used. Fractional anisot- The superior longitudinal fasciculus consists mainly of ropy and tractography was performed using Volume- the long curved fibers with posterior end points in the One software (http://www.volume-one.org/). The supe- temporal cortex and a bundle of rather horizontal fibers rior longitudinal fasciculus containing the arcuate whose posterior end points are located in the parietal lobe fasciculus fibers was sought in a coronal plane at the level (Figure 3). The curved fibers correspond to the arcuate of the rostral aspect of the splenium. The tract appears fasciculus, a tract considered crucial for the communi- normally as a green triangle lateral to the blue descend- cation between receptive and expressive language brain ing fibers of the corticospinal tracts (Figure 2), from areas.5-7 Lesions of the arcuate fasciculus result in a de- where the arcuate fasciculus can be tracked (Figure 3). ficiency in the capacity to repeat, a syndrome that has This area was contoured bilaterally defining the seeding been coined “conduction aphasia.” Other authors have region of interest (ROI). Tract propagation was termi- proposed that the arcuate fasciculus also plays a role in nated when the tract trajectory reached a voxel with frac- intelligence8 and nonlanguage cognitive functions.9 tional anisotropy less than 0.13 or when the angle be- The absence of the arcuate fasciculus in our 2 cases tween 2 consecutive steps was greater than 45°. Fractional provides an opportunity to look into its role. We were anisotropy and apparent diffusion coefficients values were more concerned in what has been preserved as opposed obtained from the inferior occipitofrontal fasciculi, cin- to the deficit, since our cases have many other cortical gulum (single coronal ROIs at the level of the anterior abnormalities that could be the cause of any cognitive commissure), the inferior longitudinal fasciculi in con- or motor deficiency. Looking at what has been pre- junction with the inferior occipitofrontal fasciculi (single served gives us an idea of what the arcuate fasciculus is coronal ROI at the level of the retrosplenial surface), and not involved in. the internal capsules (single axial ROI at the level of the Automatized language (eg, reciting automatic series) thalamus) (Figures 4, 5, and 6). and delayed recall of verbal and nonverbal material was

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Figure 6. Tractography of the superior longitudinal fasciculi in case 2. The tracts are color coded for laterality: red, left; yellow, right. Notice the absence of the arcuate fasciculus component in both sides. A indicates anterior; P, posterior.

seems supported by a recent report of intraoperative electrophysiological studies that have shown the arcu- 10,11 Figure 4. Fractional anisotropy and color-coded directional map of case ate fasciculus transmits phonological cues. How- 1.The coronal cut location is similar to the one used for Figure 2. Notice the ever, concomitant cortical and connectivity findings absence of the green anteroposterior bundle lateral to the blue corticospinal confound this observation. tract that defines the superior longitudinal fasciculus. Arrows point to the estimated location they should appear. The role of the arcuate fasciculus (and the entire superior longitudinal fasciculus) in speech and language is not completely understood. Normal volunteers show a longer left arcuate fasciculus, with more fibers, and higher fractional anisotropy values. Moreover, in many cases, the right arcuate fasciculus is nonexistent.12-14 Strikingly, left arcuate fasciculus dominance has been reported in subjects with right hemisphere language dominance.15 More recently, lateralization of the arcuate fasciculus has been found correlated with the lateralization index of language determined by functional magnetic resonance imaging on patients with right but not left temporal lobe epilepsy.16 We present for the first time, to our knowledge, 2 cases of CBPS with bilateral absence of the arcuate fasciculi. This finding analyzed in the context of the associated clinical findings may help to understand the clinical presen- tation of the condition and further expose language organization.

Accepted for Publication: June 30, 2009. Figure 5. Fractional anisotropy and color-coded directional map of case 2. Correspondence: Byron Bernal, MD, 3100 SW 62nd Ave, Rudimentary superior longitudinal fasciculi are observed in both sides Miami, FL 33176 ([email protected]). (arrows). Author Contributions: Study concept and design: Bernal. Acquisition of data: Bernal, Rey, Dunoyer, and Shan- bhag. Analysis and interpretation of data: Bernal, Rey, and preserved in both patients. Strikingly, no report of con- Altman. Drafting of the manuscript: Bernal, Rey, and Du- duction aphasia was mentioned. Therefore, at least for noyer. Critical revision of the manuscript for important in- these 2 patients, the arcuate fasciculus was not needed tellectual content: Bernal, Rey, Shanbhag, and Altman. Ad- for these functions. The common clinical findings in these ministrative, technical, and material support: Dunoyer. Study cases with arcuate fasciculus agenesis were delayed speech supervision: Bernal, Rey, and Altman. development with poor articulation and poor prosody and Financial Disclosure: None reported. other aspects of speech. In addition, both patients showed poor phonemic and semantic word generation, and dif- REFERENCES ficulties in visuospatial, organization/assembly skills, that may prompt a diagnosis of constructional apraxia. 1. Gropman AL, Barkovich AJ, Vezina LG, Conry JA, Dubovsky EC, Packer RJ. The idea to attribute the phonological difficulties of Pediatric congenital bilateral perisylvian syndrome: clinical and MRI features in our patients merely to the arcuate fasciculus absence 12 patients. Neuropediatrics. 1997;28(4):198-203.

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©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 2. Kuzniecky R, Andermann F, Guerrini R. The epileptic spectrum in the congenital gitudinal fasciculus play a role in language? a brain stimulation study. Brain. 2007; bilateral perisylvian syndrome: CBPS Multicenter Collaborative Study. Neurology. 130(pt 3):623-629. 1994;44(3, pt 1):379-385. 11. Duffau H, Peggy Gatignol ST, Mandonnet E, Capelle L, Taillandier L. Intraopera- 3. Guerrini R, Carrozzo R. Epileptogenic brain malformations: clinical presenta- tive subcortical stimulation mapping of language pathways in a consecutive se- tion, malformative patterns and indications for genetic testing. Seizure. 2002; ries of 115 patients with grade II glioma in the left dominant hemisphere. 11(suppl A):532-543. J Neurosurg. 2008;109(3):461-471. 4. Guerrini R. Genetic malformations of the cerebral cortex and epilepsy. Epilepsia. 12. Powell HW, Parker GJ, Alexander DC, et al. Hemispheric asymmetries in language- 2005;46(suppl 1):32-37. related pathways: a combined functional MRI and tractography study. Neuroimage. 5. Geschwind N. Disconnexion syndromes in animals and man: II. Brain. 1965;88 2006;32(1):388-399. (3):585-644. 13. Nucifora PG, Verma R, Melhem ER, Gur RE, Gur RC. Leftward asymmetry in rela- 6. Geschwind N. The organization of language and the brain. Science. 1970;170(961): tive fiber density of the arcuate fasciculus. Neuroreport. 2005;16(8):791-794. 940-944. 14. Parker GJ, Luzzi S, Alexander DC, Wheeler-Kingshott CA, Ciccarelli O, Lambon 7. Wernicke C. The aphasic symptom complex: a psychological study on a neuro- Ralph MA. Lateralization of ventral and dorsal auditory-language pathways in the logical basis. Boston Stud Philos Sci. 1874:4. human brain. Neuroimage. 2005;24(3):656-666. 8. Jung RE, Haier RJ. The Parieto-Frontal Integration Theory (P-FIT) of intelli- 15. Vernooij MW, Smits M, Wielopolski PA, Houston GC, Krestin GP, van der Lugt gence: converging neuroimaging evidence. Behav Brain Sci. 2007;30(2):135- A. Fiber density asymmetry of the arcuate fasciculus in relation to functional hemi- 154. spheric language lateralization in both right- and left-handed healthy subjects: a 9. Sundaram SK, Sivaswamy L, Makki MI, Behen ME, Chugani HT. Absence of ar- combined fMRI and DTI study. Neuroimage. 2007;35(3):1064-1076. cuate fasciculus in children with global developmental delay of unknown etiol- 16. Rodrigo S, Oppenheim C, Chassoux F, et al. Language lateralization in temporal ogy: a diffusion tensor imaging study. J Pediatr. 2008;152(2):250-255. lobe epilepsy using functional MRI and probabilistic tractography. Epilepsia. 2008; 10. Mandonnet E, Nouet A, Gatignol P, Capelle L, Duffau H. Does the left inferior lon- 49(8):1367-1376.

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