□ CASE REPORT □ Extensive Callosal Infarction Showing Difficulty in Knitting as an Initial Symptom Keisuke Suzuki 1, Yoshiteru Takiguchi 1, Tomoyuki Miyamoto 2, Masayuki Miyamoto 2, Koichi Hirata 2, Kenji Hara 1, Shiho Suzuki 2, Kohzo Takebayashi 1, Yoshimasa Aso 1 and Toshihiko Inukai 1 Abstract A 66-year-old right-handed woman with type 2 diabetes mellitus was admitted to our hospital with progressive dysarthria and gait disturbance preceded by difficulty in knitting. Brain magnetic resonance imaging (MRI) showed a lesion involving the entire corpus callosum. Although tumor was considered in the differential diagnosis because of the atypical imaging findings, she was diagnosed with infarction based on clinical improvement after admission and sequential changes in MRI. We suggest that difficulty in knitting may be an important early manifestation of a callosal disconnection syndrome and that follow-up clinical and imaging examinations would contribute to confirmation of the diagnosis. Key words: corpus callosum, disconnection syndrome, knitting, infarction, brain magnetic resonance imaging (Inter Med 47: 1431-1435, 2008) (DOI: 10.2169/internalmedicine.47.1095) Introduction The corpus callosum contains nerve fibers that functionally connect the two cerebral hemispheres and that make an important contribution to interhemispheric integration (1). A lesion of the corpus callosum can cause many forms of higher cortical dysfunction, including disconnection syndromes such as alien hand syndrome and diagonistic dyspraxia (2-4). Callosal infarction is extremely rare because the corpus callosum has a rich blood supply: ordinarily, its rami are protected by perfusion via penetrating arteries arising from parent arteries at right angles, thereby providing relative resistance to lacunar strokes, microvascular disease, atherothrombosis, and embolism (5-7). Corpus callosum infarction can present various neurologic signs and follow a slow progressive clinical course with atypical radiologic features, such as crossing of the midline and a contrast enhancement pattern that suggests a diagnosis of tumor rather than infarction. Three of five previous patients with callosal infarction underwent biopsy because of an unusual clinical course and atypical brain imaging findings (6). We report a rare occurrence of extensive callosal infarction attributable to atherothrombosis, where the initial symptom was difficulty in knitting. The initial imaging findings were difficult to differentiate from those of tumor. Case Report In mid-March 2007, a 66-year-old right-handed woman attempted to complete a half-finished knitted sweater for her daughter but was impeded by a new disturbance of bimanual coordination. Family members noted no changes in the patient, as she experienced no problems in carrying out other daily activities such as cooking, eating, bathing, and cleaning. The patient had been a knitter for 12 years and had become able to knit almost any pattern from memory. Two days after the first episode, she developed bilateral lower limb weakness that lasted for several minutes; a week later, she noted a speech difficulty and was subsequently admitted to our hospital in early April. The patient had type 2 diabetes mellitus for 12 years, receiving voglibose 0.9 mg/day 1 Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya and 2Department of Neurology, Dokkyo Medical University, Tochigi Received for publication March 8, 2008; Accepted for publication May 9, 2008 Correspondence to Dr. Keisuke Suzuki, keisuke@dokkyomed.ac.jp 1431 Inter Med 47: 1431-1435, 2008 DOI: 10.2169/internalmedicine.47.1095 Fi g ur e1 . Sa g i t t a l( A)a nda x i a l( B,F)FLAI Ri ma g e so fbr a i n( TR,8 , 0 0 0ms e c ;TE,1 2 0ms e c ) s ho w hi g hs i g na li nt e ns i t yi nt hee nt i r ec o r pusc a l l o s um o na dmi s s i o n( Apr i l2 ) .E:T1 -we i g ht e d s a g i t t a le nha nc e dMRi ma g e s( TR,4 6 0ms e c ;TE,1 5ms e c )s ho we nha nc e me nto ft hea nt e r i o rc o r pusc a l l o s um ( e x c e ptf o rt hes pl e ni um)o nho s pi t a lda y3 .Ax i a lFLAI Ri ma g e so nMa y1 6( C,G) s ho w noc ha ng ei nt hee x t e nto fhi g hs i g na li nt e ns i t yi nt hec o r pusc a l l o s um.OnJ ul y1 8( D,H) , FLAI Ri ma g e sde mo ns t r a t e ds l i g htr e duc t i o no ft hea r e ao fhy pe r i nt e ns i t ya r e ai nt hea nt e r i o rc o r pusc a l l o s um ( a r r o w) . and insulin treatment for the past 3 months. Seventeen years before admission she underwent partial pancreatectomy and splenectomy for a pancreatic pseudocyst that arose following traumatic injury. The patient had no prior history of tobacco or alcohol use. On admission, the patient was 150.0 cm tall and weighed 43.0 kg, with a body mass index of 19.1 kg/m2. Her body temperature was 36.6°C, and the pulse was regular at 64/ min; blood pressure was 138/88 mmHg. Physical examination findings in the chest and abdomen were unremarkable except for the old surgical scar. The patient was alert but showed dysarthria, right-sided truncal ataxia and dysdiadochokinesis, and a disconnection syndrome with left tactile extinction, left agraphia, and diagonistic dyspraxia. In attempting to move her right hand, her left hand moved involuntarily, against her will. Tendon reflexes were increased symmetrically without Babinski’s sign. Motor and sensory systems were intact. The patient, who had 12 years of education, scored 25/30 on the Mini-Mental State Examination (impaired items were related to attention and calculation, a 3-stage command, and the copying of a drawing of an intersecting pentagon), and rated 4 on the National Institutes of Health Stroke Scale. Laboratory analysis revealed a fasting blood glucose level of 336 mg/dL; glycosylated hemoglobin (HbA1C), 9.0%; and glycosylated albumin, 32.6%. Urinanalysis showed glucosuria (3+). Prothrombin and partial prothrombin times were normal, but D-dimer was increased (3.6 μg/mL). Concentrations of serum electrolyte, thyroid hormone, ammonia, and vitamin B1 were normal. Lumbar puncture yielded clear cerebrospinal fluid with a cell count of 2/μL; protein and glucose concentrations were 55 and 143 mg/dL, respectively. Chest radiography showed no abnormalities, and electrocardiography yielded a normal tracing. Brain magnetic resonance imaging (MRI) obtained on admission demonstrated a lesion involving the entire corpus callosum, with hyperintensity on the fluid-attenuated inversion recovery (FLAIR) images (Fig. 1A, B, F). Diffusionweighted imaging (DWI) showed high signal intensity in most of the area of FLAIR abnormality, with correspondingly restricted apparent diffusion coefficient (ADC) maps (Fig. 2A, B, E, F). On post-contrast T1-weighted images on the third hospital day, abnormal enhancement was observed in the anterior part of the corpus callosum, including the genu and body (Fig. 1E). Magnetic resonance angiography (MRA) and three-dimensional computed tomographic angiography (3D-CTA) revealed a slightly narrow and tortuous left anterior cerebral artery (ACA) compared with the right ACA, but no occlusion or severe stenosis was detected in the major cerebral arteries (Fig. 3). Electroencephalographic findings included low-amplitude alpha activity of approximately 9 Hz without epileptic discharges or slow waves. Echocardiography and Holter electrocardiography yielded no abnormal findings, with no evidence of atrial fibrillation or thrombosis. Glycemic control was difficult to maintain because the patient could not adhere to a diet. After admission, her caloric intake was limited to 1,600 kcal and the insulin dosage was increased from two to four times daily, using NovoRapid (Novo Nordisk, Tokyo) three times/day and No- 1432 Inter Med 47: 1431-1435, 2008 DOI: 10.2169/internalmedicine.47.1095 Fi g ur e2 . Ona dmi s s i o n,di f f us i o nwe i g ht e di ma g e s( DWI ;TR,2 , 5 0 0ms e c ;TE,8 2ms e c )de mo ns t r a t ehi g hs i g na li nt e ns i t yi nt hec o r pusc a l l o s um ( A,E) ,wi t hc o r r e s po ndi ngr e s t r i c t e da ppa r e nt di f f us i o nc o e f f i c i e nt( ADC)ma ps( B,F) .Onda y1 4 ,DWIs ho ws ubt l yi nc r e a s e ds i g na li nt e ns i t yi n t hec o r pusc a l l o s um ( C, G) , whi l ec o r r e s po ndi ngADCma psde t e c tnoma t c hi nga bno r ma l i t y( D, H) . Fi g ur e3 . Thr e e di me ns i o na lc o mput e dt o mo g r a phi ca ng i o g r a phy( A)a ndma g ne t i cr e s o na nc e a ng i o g r a phy( B)de mo ns t r a t eas l i g ht l yna r r o wa ndt o r t uo usl e f ta nt e r i o rc e r e br a la r t e r y( ACA) ( a r r o ws )c o mpa r e dt ot her i g htACA,wi t hnoo c c l us i o no rs e v e r es t e no s i sno t e di na nyma j o rc e r e br a la r t e r y . volin N once/day. The total daily insulin dose ranged from 26 to 40 units. Considering the longstanding presence of diabetes, cerebral infarction was suspected and aspirin therapy was initiated. Conversely, the gradually progressive initial course and MRI characteristics of the lesion, such as abnormal enhancement and crossing of the midline, are atypical for infarction; therefore, brain biopsy was to be considered if the clinical course worsened or the callosal lesion was enlarged in follow-up MRI. A follow-up brain MRI with DWI on the 14th day demonstrated a slight reduction in signal hyperintensity in the corpus callosum without any corresponding abnormality in the ADC maps (Fig. 2C, D, G, H). The patient’s neurologic symptoms gradually improved, and no extension of the corpus callosum lesion was shown by FLAIR imaging 6 weeks after admission (Fig. 1C, G). The patient was discharged 1 week later. Follow-up MRI obtained in the outpatient department 2 months after discharge demonstrated a slight reduction in the callosal hyperintense area on FLAIR images (Fig. 1D, H). 1433 Discussion On admission, the patient displayed various neurologic Inter Med 47: 1431-1435, 2008 DOI: 10.2169/internalmedicine.47.1095 Ta bl e1 . Cha r a c t e r i s t i c so fPa t i e nt swi t hCa l l o s a lDi s c o nne c t i o nSy ndr o me signs including disconnection syndrome with left tactile extinction, left agraphia, and diagonistic dyspraxia. These disconnection syndromes are common in lesions of the corpus callosum and are thought to reflect dysfunction of interhemispheric neuronal connections (2, 8). During the 3 weeks before admission, the patient had experienced difficulty only in knitting, while being able to carry out all other daily activities. We believe that she was otherwise neurologically asymptomatic at that time, and that her difficulty in knitting resulted from impaired integration of bimanual movements attributable to a callosal disconnection syndrome. Impairment of complex synergistic upper-limb movements or bimanual coordinative movements is recognized as a disconnection syndrome arising from a callosal disorder (9, 10). Although most knitting patterns require the use of only two stitches, knit and purl, expert knitters such as the current patient develop numerous knitting techniques and follow patterns that include relatively repetitive, complex, and synergistic movements. Knitting is reported to have relaxing effects, including decreased heart rate, reduced blood pressure, and enhanced muscle tone (11), and has been linked with a decreased risk of developing dementia in a cohort study of 2,040 persons (12); however, to the best of our knowledge a disturbance involving knitting as the initial or sole symptom of callosal infarction has not been previously reported, and the specific interactions between knitting and the corpus callosum were unknown. Table 1 lists the unique symptoms related to impairment of daily activities due to a callosal lesion (13-16). Callosal infarction presents with an acute or slowly progressive course and nonlocalising neurologic signs, thereby causing considerable difficulty in making a clinical diagnosis of infarction (6, 7). Similarly, in our patient we would hesitate to regard the initial symptom of difficulty in knitting as a new localized symptom; her clinical course also appears atypical for stroke. Friese et al (17) described infarction of the corpus callosum as being more central in location and smaller in size than a tumor or inflammatory lesion of the corpus callosum, given the rich bilateral blood supply from both the ACAs and posterior cerebral arteries (PCAs). As for the specific location of corpus callosum infarctions, embolism may be more frequent in the splenium (18), while atherothrombotic infarcts are possibly more frequent in the genu and body (6). Although rare, extensive callosal infarction including the rostrum, genu, body, and splenium have occurred from embolism (7) or hemodynamic instability (19), while atherothrombosis was suspected in the present case, given the presence of longstanding diabetes in the absence of cardiac abnormalities. Typically, the corpus callosum receives a rich blood supply from three vessels. The pericallosal branch of the ACA is the main vascular supply to most of the body of the corpus callosum. The subcallosal and medial callosal branch supply the anterior portion of the corpus callosum, i.e., the rostrum and genu; the posterior pericallosal branch of the 1434 Inter Med 47: 1431-1435, 2008 DOI: 10.2169/internalmedicine.47.1095 PCA supplies the posterior half of the corpus callosum, i.e., the splenium (18, 20). According to a microsurgical study involving common variations, in 7.5% of 40 hemispheres a pericallosal branch either did not pass between the hemispheres along the corpus callosum or did not supply it. Furthermore, 30% of 20 specimens gave rise to a medial callosal branch of the anterior communicating artery, supplying other regions in addition to the anterior corpus callosum (20). In the present case, the callosal lesion involved the entire structure, and MRA and 3D-CTA disclosed no severe stenosis or intracranial arterial occlusion. This suggests that an artery other than the ACA or PCA, such as the medial callosal branch of anterior communicating artery, might have been dominant in terms of supply to the entire corpus callosum. Differential diagnosis of callosal lesions includes multiple sclerosis, malignant lymphoma, glioblastoma, and trauma (21, 22). In addition, callosal infarction often shows atypical clinical and radiographic features suggestive of tumor (6, 7). Although we did not perform magnetic resonance spectroscopy or angiography in our case, the DWI findings and corresponding restricted ADC map obtained by MRI were consistent with subacute ischemic changes causing a corpus callosum lesion (7, 19). While lymphoma―a common tumor that can involve the corpus callosum and show restricted diffusion on ADC maps (23)―was a consideration, in our case an improving clinical course including follow-up DWI and FLAIR MRI findings with decreasing signal hyperintensity led us to rule out lymphoma. In conclusion, we report a patient with extensive callosal infarction from atherothrombosis related to underlying type 2 diabetes mellitus. In this callosal infarction, clinical follow-up and follow-up MRI contributed to confirmation of the diagnosis and enabled us to avoid biopsy. The symptom of difficulty in knitting was considered to suggest involvement of the corpus callosum as a disconnection syndrome. References 1. Pandya DN, Seltzer B. The topography of commissural fibers. In: Two Hemispheres-One Brain: Functions of the Corpus Callosum. Lepre F, Ptito M, Jasper HH, Eds. Alan R. Liss, New York, 1986: 44-73. 2. Watson RT, Heilman KM. Callosal apraxia. Brain 106: 391-403, 1983. 3. Suwanwela NC, Leelacheavasit N. Isolated corpus callosal infarction secondary to pericallosal artery disease presenting as alien hand syndrome. J Neurol Neurosurg Psychiatry 72: 533-536, 2002. 4. Kumral E, Kocaer T, Sagduyu A, et al. Callosal infarction after bilateral occlusion of the internal carotid arteries with hemineglect syndrome and astasia-abasia. Rev Neurol (Paris) 151: 202-205, 1995. 5. Moody DM, Bell MA, Challa VR. 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 9: 1051-1059, 1988. 6. Kasow DL, Destian S, Braun C, Quintas JC, Kagetsu NJ, Johnson CE. Corpus callosum infarcts with atypical clinical and radiologic presentations. AJNR Am J Neuroradiol 21: 1876-1880, 2000. 7. Riedy G, Melhem ER. Acute infarct of the corpus callosum: appearance on diffusion-weighted MR imaging and MR spectroscopy. J Magn Reson 18: 255-259, 2003. 8. Giroud M, Dumas R. Clinical and topographical range of callosal infarction: a clinical and radiological correlation study. J Neurol Neurosurg Psychiatry 59: 238-242, 1995. 9. Zaidel D, Sperry RW. Some long-term motor effects of cerebral commissurotomy in man. Neuropsychologia 15: 193-204, 1977. 10. Gazzaniga MS. Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? 123: 1293-1326, 2000. 11. Dittrich LR. Knitting. Acad Med 76: 671, 2001. 12. Fabrigoule C, Letenneur L, Dartigues JF, Zarrouk M, Commenges D, Barberger-Gateau P. Social and leisure activities and risk of dementia: a prospective longitudinal study. J Am Geriatr Soc 43: 485-490, 1995. 13. Suzuki K, Yamadori A, Endo K, Fujii T, Ezura M, Takahashi A. Dissociation of letter and picture naming resulting from callosal disconnection. Neurology 51: 1390-1394, 1998. 14. Nishikawa T, Okuda J, Mizuta I, et al. Conflict of intentions due to callosal disconnection. J Neurol Neurosurg Psychiatry 71: 462471, 2001. 15. Nyffeler T, Bühler R, Höllinger P, Hess CW. Reversible callosal disconnection syndrome in internal hydrocephalus. J Neurol Neurosurg Psychiatry 74: 389-491, 2003. 16. Satoh M, Furukawa K, Takeda K, Kuzuhara S. Left hemianomia of musical symbols caused by callosal infarction. J Neurol Neurosurg Psychiatry 77: 705-706, 2006. 17. Friese SA, Bitzer M, Freudenstein D, Voigt K, Küker W. Classification of acquired lesions of the corpus callosum with MRI. Neuroradiology 42: 795-802, 2000. 18. Chrysikopoulos H, Andreou J, Roussakis A, Pappas J. Infarction of the corpus callosum: computed tomography and magnetic resonance imaging. Eur J Radiol 25: 2-8, 1997. 19. Spengos K, Tsivgoulis G, Chatziioannou A, Potagas C, Zakopoulos N, Zis V. Extensive corpus callosum infarction: an uncommon pattern of watershed ischaemia? J Neurol 253: 1646-1648, 2006. 20. Türe U, Yasargil G, Krisht AF. The arteries of the corpus callosum: a microsurgical anatomic study. Neurosurgery 39: 10751085, 1996. 21. Uchino A, Takase Y, Nomiyama K, Egashira R, Kudo S. Acquired lesions of the corpus callosum: MR imaging. Eur Radiol 16: 905914, 2006. 22. Georgy BA, Hesselink JR, Jernigan TL. MR imaging of the corpus callosum. AJR Am J Roentgenol 160: 949-955, 1993. 23. Toh CH, Chen YL, Hsieh TC, Jung SM, Wong HF, Ng SH. Glioblastoma multiforme with diffusion-weighted magnetic resonance imaging characteristics mimicking primary brain lymphoma: case report. J Neurosurg 105: 132-135, 2006. Ⓒ 2008 The Japanese Society of Internal Medicine http://www.naika.or.jp/imindex.html 1435