- Email: [email protected]
Thalamic aphasia secondary to glioblastoma multiforme
Journal of Clinical Neuroscience xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Thalamic aphasia secondary to glioblastoma multiforme Amjad Samara a,b, Brent Berry c, Malik Ghannam c,⇑ a
Arkansas Children’s Nutrition Center, Little Rock, AR, USA Faculty of Medicine and Health Sciences, An-Najah National University, Palestine c Department of Neurology, University of Minnesota, Minneapolis, MN, USA b
a r t i c l e
i n f o
Article history: Received 31 October 2019 Accepted 12 January 2020 Available online xxxx Keywords: Thalamic aphasia Glioblastoma multiforme Language function Magnetic resonance imaging
a b s t r a c t Background: Thalamic aphasia is an unusual clinical presentation of brain neoplasm with few cases reported. Herein, we present a case of an adult woman with thalamic aphasia due to glioblastoma of the thalamus. Case presentation: A 57-year-old female patient presented with difficulty walking, slow speech and cognition and altered mental status. At baseline, she was conversant and interactive. Physical examination showed right hemiparesis in addition to word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. The remaining neurological exam was otherwise unremarkable. Brain CT and brain MRI scans showed a left thalamic lesion that is centrally necrotic and peripherally enhancing suggestive of a high-grade neoplasm. Eventually, histopathological examination of brain biopsy confirmed the diagnosis of glioblastoma multiforme. Thalamic aphasia was proposed as an explanation for the neurological symptoms observed in this patient. Conclusions: This patient demonstrates an unusual presentation of glioblastoma multiforme as thalamic aphasia. It may also point to the potential contribution of the understanding of how thalamic aphasia evolves to characterize the role of the thalamus in language functions. Published by Elsevier Ltd.
1. Background Glioblastoma multiforme (GBM) is the most common and the most aggressive primary brain tumor in adults. The annual incidence of GBM ranges between 2 and 3 per 100,000 population, and it most commonly presents after the sixth decade of life [1]. The pathogenesis is multifactorial, and there are no known preventive measures. There is an increased risk of GBM in individuals with certain hereditary CNS conditions like neurofibromatosis, Li–Fraumeni syndrome, Turcot’s syndrome and tuberous sclerosis [2–4]. The GBM presents with a wide range of neurological symptoms including headaches, seizures, focal neurological deficits and signs of increased intracranial pressure [5]. Brain imaging studies like CT and MRI are used to support the diagnosis of GBM, but the histopathological examination of brain biopsy confirms the Abbreviations: CT, Computed tomography; DWI, Diffusion-weighted imaging; FLAIR, Fluid-attenuated inversion recovery; GBM, Glioblastoma multiforme; IDH-1, Isocitrate dehydrogenase-1; IDH-2, Isocitrate dehydrogenase-2; MGMT, O6-methyl guanine-DNA-methyltransferase; MRI, Magnetic resonance imaging; WHO, World health organization. ⇑ Corresponding author at: 12-181 Phillips Wangensteen Building, 516 Delaware St. SE, Minneapolis, MN 55455, USA. E-mail address: [email protected] (M. Ghannam).
definitive diagnosis. The median survival after diagnosis is 12 to 15 months with 2-year survival rate between 10% and 27% [6].
2. Case presentation A 57-year-old African American woman with past medical history of hypertension, depression, anxiety, gastroesophageal reflux disease, asthma, and rheumatoid arthritis; treated with methotrexate and etanercept, initially presented to the emergency department after the patient’s daughter noted difficulty walking and abnormally slow speech and cognition. Besides, she was also complaining of frequent headaches and difficulty remembering things over the past several weeks. A comprehensive review of the systems was otherwise unremarkable. Physical examination showed altered mental status, right-sided weakness, word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. On the day of presentation, she underwent a head CT scan that showed an infiltrating lesion centered in the left thalamus with a suspicious area of central necrosis suggestive of high-grade neoplasm (Fig. 1). Moreover, effacement of the third ventricle and mild to moderate enlargement of the lateral ventricles were also noted. Therefore, the
https://doi.org/10.1016/j.jocn.2020.01.063 0967-5868/Published by Elsevier Ltd.
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
2
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 1. (a, b, c): Computed tomography (CT) images of the reported case on presentation showing an infiltrating lesion in the left thalamus with features suggestive of a highgrade neoplasm. (d): Axial T1-weighted image; (e): Axial T1-weighted image post-contrast administration; (f): Fluid attenuation inversion recovery (FLAIR) image; (g) Apparent Diffusion Coefficient (ADC) map; (h): Coronal T2-weighted image.
patient underwent further imaging with a brain MRI scan. Brain MRI showed mixed signal intensity, heterogeneously enhancing mass centered in the left thalamus and extending to involve the left aspect of the upper brainstem (Figs. 1 and 2). There was also a bilobed peripherally enhancing component with suspected areas of central necrosis and tiny foci of hemosiderin staining. This appearance favored a neoplastic process as the underlying cause. Also, there was a mass effect compressing the posterior third ventricle and proximal cerebral aqueduct with findings concerning for mild obstructive supratentorial hydrocephalus. There was a larger area of surrounding infiltrative T2/FLAIR hyperintensity without associated enhancement likely representing a combination of infiltrative neoplasm and vasogenic edema that extended into the left posterior lentiform white matter in the left aspect of the upper brainstem. At this point, the patient was started on dexamethasone and admitted to the hospital for further management. On further diagnostic workup, the patient underwent chest, abdomen, and pelvis CT scan which revealed no evidence of primary malignancy
or metastatic disease. Stereotactic biopsy was advised to reach a definitive diagnosis. The patient underwent brain biopsy with subsequent histopathological examination was suggestive of glioblastoma (Fig. 3). MGMT promoter methylation, IDH1 and IDH2 mutations were not identified. The final diagnosis was assigned as glioblastoma of the left thalamus (WHO Grade IV glial neoplasm). Over the course of next several months, the patient was followed up by our neuro-oncology team and treated with concurrent chemoradiation followed by further adjuvant temozolomide. 3. Discussion Thalamic aphasia is a language dysfunction associated with lesions exclusively affecting the thalamus (usually the left side). Thalamic aphasia may develop in isolated hemorrhagic and ischemic strokes [7,8]. Less frequently, it was also documented in cases of malignant neoplasms involving the thalamus [9], and neuro-surgical interventions [10]. The clinical presentation of
Fig. 2. MRI (DWI) showing a mild mass effect on the posterior margin of the third ventricle (red arrow). MRI (T1-Post contrast) showing ring-enhancing lesion centered within the dorsal medial left thalamus with central necrosis (green arrow). MRI perfusion is demonstrating heterogeneous peripheral diffusion restriction with intra-lesional hemosiderin staining (yellow arrow).
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
3
Fig. 3. Photomicrographs, Hematoxylin and eosin stain, show histopathology of brain biopsy. (a): Vessels with endothelial proliferation, resulting in ischemia and abundant necrosis; (b): area of necrosis, tumor cell shadowing (dead cells) and gemistocytes (arrow); (c): Focus of residual viable tumor cells (astrocytes); (d): Mitotic figure (arrow).
thalamic aphasia varies, and it can present as global aphasia, expressive aphasia, or transcortical aphasia [8]. The most common presentation is transcortical aphasia; transcortical motor aphasia (hesitant and fragmented speech) or transcortical sensory aphasia (poor comprehension, semantic paraphasias, and echolalia) [8]. The distinguishing characteristic of both transcortical aphasia subtypes and a prominent feature of thalamic aphasia is intact and strongly preserved repetition. Other notable findings may include paraphasias [11]. Thalamic aphasia most commonly presents after lesions affecting the left (dominant) thalamus, but cases of aphasia in rightsided lesions were also noted in left-handed patients [12]. It has been proposed that disconnecting thalamic projections to language-related cortical regions is the underlying mechanism of language deficits associated with thalamic lesions [13]. Fig. 4 shows a schematic diagram of the connections between various thalamic nuclei and corresponding cortical areas. Nevertheless, the exact underlying pathophysiological mechanism for the development of thalamic aphasia is still controversial. Thalamic aphasia was reported in vascular lesions involving all vascular territories supplying the different thalamic nuclei (tuberothalamic, paramedian, inferolateral and posterior choroidal arteries) [14]. However, the occurrence of thalamic aphasia has been reported to be higher following hemorrhage affecting the posterior thalamus (pulvinar) in contrast to infarctions affecting the anterior thalamic circulation via tuberothalamic artery (ventral and anterior nuclei) [15]. For an extended period, the clinical-pathological correlative approach has been adopted to explain thalamus contribution in language functions and to explain the mechanism of aphasia following thalamic lesion. Using this approach, most of the thalamic nuclei have been mentioned to contribute to language functions, most notably
ventral lateral nucleus and pulvinar [15]. However, this approach may lead to inaccurate conclusions especially in cases of thalamic hemorrhage. The attempt to explain the neuropsychological symptoms based on hemorrhage location would be erroneous because the expanding hematoma exerts pressure on the surrounding structures and alter the pattern of symptoms. Recent advances in functional neuroimaging technologies enable more accurate conclusions about the thalamus role in language processing. For example, a tractography study showed that Broca’s area is structurally connected to the thalamus (ventral anterior nucleus and pulvinar) and suggested that this network is involved in language processing [16]. Other functional neuroimaging techniques like functional MRI and magnetoencephalography [17,18]. Regarding thalamic aphasia, one study suggested that aphasia associated with thalamic lesions is consistent with the ‘‘selective engagement model” proposed by Crosson [19,20]. In this model, Crosson et al. proposed that the thalamus monitors, controls and integrates the activity in language-related cortical areas (receptive and expressive). Other linguistic models suggested different roles of the thalamus in language that include word alternatives selection, semantic monitoring, and release of cortically formed responses [21]. It is also worth mentioning here that some studies reported concurrent cortical hypoperfusion in language cortical regions in some cases of thalamic aphasia which may indicate a contribution of cortical dysfunction in the neural basis of the thalamic aphasia [22,23]. Future functional neuroimaging research will be helpful in revealing the whole relationship between the thalamus and language and the specific neural basis of thalamus aphasia. From a clinician point of view, physicians utilize a battery of neuropsychological tests for the comprehensive evaluation of aphasias (spoken language, writing, and reading comprehension).
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
4
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 4. A schematic diagram demonstrating the connection between thalamic nuclei and their corresponding cortical areas.
In 1984, Crosson suggested a set of clinical criteria to assist in the diagnosis of thalamic aphasia [10]. Crosson’s definition included: 1) fluent output with frequent paraphasia (mainly semantic); 2) Jargon (severe paraphasia); 3) less severe deficits in auditory comprehension; 4) intact or minimally impaired repetition. In our case, at least two of the four criteria were present. Besides, right-sided weakness, reading and writing impairment were also observed. The explanation for the right-sided weakness could be the direct involvement of the adjacent internal capsule or mass effect of peri-tumor edema. Brain MRI scans are used to support the diagnosis of GBM. It usually appears as a ring-enhancing lesion (centrally necrotic and peripherally enhancing) although this is not specific. Definitive diagnosis requires stereotactic biopsy or tumor resection after craniotomy. The management and the prognosis of thalamic aphasia largely depend on the underlying cause – hemorrhage, infarction, or tumor. In cases of thalamic hemorrhage, the clinical outcome is affected by the size of hematoma, affected nuclei, and extension to adjacent structures [8,24]. Thalamic aphasia due to vascular lesions may resolve after variable periods of time although persistence of residual language dysfunction is a common outcome that requires serious attention [10]. In our case, glioblastoma multiforme is very difficult to treat, and a combination of surgery, radiotherapy, and other treatment modalities will be necessary. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgment Not applicable. Funding Not applicable. Availability of data and material The data that support the findings and conclusions are included in this published article.
Authors’ contributions MG: concept and design of the study. AS & BB: Drafting and editing of the manuscript. MG: critical revision of the manuscript for important intellectual content, read and approved the final manuscript. Consent for publication Informed consent for publication of this case report and any accompanying images was obtained from the patient. Ethics approval and consent to participate The authors declare that ethics approval was not required for this case report. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2020.01.063. References [1] Ohgaki H et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res 2004;64(19):6892–9. [2] Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet 2001;68(5):1110–8. [3] Kleihues P, Ohgaki H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1999;1(1):44–51. [4] Hamilton SR et al. The molecular basis of Turcot’s syndrome. N Engl J Med 1995;332(13):839–47. [5] Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA 2013;310(17):1842–50. [6] Stupp R et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352(10):987–96. [7] Tuszynski MH, Petito CK. Ischemic thalamic aphasia with pathologic confirmation. Neurology 1988;38(5):800–2. [8] Kumral E et al. Thalamic hemorrhage. A prospective study of 100 patients. Stroke 1995;26(6):964–70. [9] Roosen N et al. Primary thalamic malignant fibrous histiocytoma of the dominant hemisphere causing severe neuropsychological symptoms. Clin Neuropathol 1989;8(1):16–21. [10] Crosson B. Role of the dominant thalamus in language: a review. Psychol Bull 1984;96(3):491–517. [11] Karussis D, Leker RR, Abramsky O. Cognitive dysfunction following thalamic stroke: a study of 16 cases and review of the literature. J Neurol Sci 2000;172 (1):25–9.
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx [12] Kirshner HS, Kistler KH. Aphasia after right thalamic hemorrhage. Arch Neurol 1982;39(10):667–9. [13] Nadeau SE, Crosson B. Subcortical aphasia. Brain Lang 1997;58(3):355–402. [14] Llano DA. Functional imaging of the thalamus in language. Brain Lang 2013;126(1):62–72. https://doi.org/10.1016/j.bandl.2012.06.004. [15] Crosson BA. Subcortical functions in language and memory. New York, NY, US: Guilford Press; 1992. [16] Bohsali AA et al. Broca’s area – thalamic connectivity. Brain Lang 2015;141:80–8. [17] David O et al. Dynamic causal modeling of subcortical connectivity of language. J Neurosci 2011;31(7):2712–7. [18] Ketteler D et al. The subcortical role of language processing. High level linguistic features such as ambiguity-resolution and the human brain; an fMRI study. Neuroimage 2008;39(4):2002–9.
5
[19] Crosson B. Subcortical functions in language: a working model. Brain Lang 1985;25(2):257–92. [20] Metz-Lutz MN et al. Language functional neuro-imaging changes following focal left thalamic infarction. NeuroReport 2000;11(13):2907–12. [21] Crosson B et al. Models of subcortical functions in language: current status. J Neurolinguistics 1997;10(4):277–300. [22] Radanovic M, Scaff M. Speech and language disturbances due to subcortical lesions. Brain Lang 2003;84(3):337–52. [23] Sebastian R et al. Aphasia or neglect after thalamic stroke: the various ways they may be related to cortical hypoperfusion. Front Neurol 2014;5(231). [24] Tokgoz S et al. Clinical properties of regional thalamic hemorrhages. J Stroke Cerebrovasc Dis 2013;22(7):1006–12.
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Thalamic aphasia secondary to glioblastoma multiforme Amjad Samara a,b, Brent Berry c, Malik Ghannam c,⇑ a
Arkansas Children’s Nutrition Center, Little Rock, AR, USA Faculty of Medicine and Health Sciences, An-Najah National University, Palestine c Department of Neurology, University of Minnesota, Minneapolis, MN, USA b
a r t i c l e
i n f o
Article history: Received 31 October 2019 Accepted 12 January 2020 Available online xxxx Keywords: Thalamic aphasia Glioblastoma multiforme Language function Magnetic resonance imaging
a b s t r a c t Background: Thalamic aphasia is an unusual clinical presentation of brain neoplasm with few cases reported. Herein, we present a case of an adult woman with thalamic aphasia due to glioblastoma of the thalamus. Case presentation: A 57-year-old female patient presented with difficulty walking, slow speech and cognition and altered mental status. At baseline, she was conversant and interactive. Physical examination showed right hemiparesis in addition to word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. The remaining neurological exam was otherwise unremarkable. Brain CT and brain MRI scans showed a left thalamic lesion that is centrally necrotic and peripherally enhancing suggestive of a high-grade neoplasm. Eventually, histopathological examination of brain biopsy confirmed the diagnosis of glioblastoma multiforme. Thalamic aphasia was proposed as an explanation for the neurological symptoms observed in this patient. Conclusions: This patient demonstrates an unusual presentation of glioblastoma multiforme as thalamic aphasia. It may also point to the potential contribution of the understanding of how thalamic aphasia evolves to characterize the role of the thalamus in language functions. Published by Elsevier Ltd.
1. Background Glioblastoma multiforme (GBM) is the most common and the most aggressive primary brain tumor in adults. The annual incidence of GBM ranges between 2 and 3 per 100,000 population, and it most commonly presents after the sixth decade of life [1]. The pathogenesis is multifactorial, and there are no known preventive measures. There is an increased risk of GBM in individuals with certain hereditary CNS conditions like neurofibromatosis, Li–Fraumeni syndrome, Turcot’s syndrome and tuberous sclerosis [2–4]. The GBM presents with a wide range of neurological symptoms including headaches, seizures, focal neurological deficits and signs of increased intracranial pressure [5]. Brain imaging studies like CT and MRI are used to support the diagnosis of GBM, but the histopathological examination of brain biopsy confirms the Abbreviations: CT, Computed tomography; DWI, Diffusion-weighted imaging; FLAIR, Fluid-attenuated inversion recovery; GBM, Glioblastoma multiforme; IDH-1, Isocitrate dehydrogenase-1; IDH-2, Isocitrate dehydrogenase-2; MGMT, O6-methyl guanine-DNA-methyltransferase; MRI, Magnetic resonance imaging; WHO, World health organization. ⇑ Corresponding author at: 12-181 Phillips Wangensteen Building, 516 Delaware St. SE, Minneapolis, MN 55455, USA. E-mail address: [email protected] (M. Ghannam).
definitive diagnosis. The median survival after diagnosis is 12 to 15 months with 2-year survival rate between 10% and 27% [6].
2. Case presentation A 57-year-old African American woman with past medical history of hypertension, depression, anxiety, gastroesophageal reflux disease, asthma, and rheumatoid arthritis; treated with methotrexate and etanercept, initially presented to the emergency department after the patient’s daughter noted difficulty walking and abnormally slow speech and cognition. Besides, she was also complaining of frequent headaches and difficulty remembering things over the past several weeks. A comprehensive review of the systems was otherwise unremarkable. Physical examination showed altered mental status, right-sided weakness, word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. On the day of presentation, she underwent a head CT scan that showed an infiltrating lesion centered in the left thalamus with a suspicious area of central necrosis suggestive of high-grade neoplasm (Fig. 1). Moreover, effacement of the third ventricle and mild to moderate enlargement of the lateral ventricles were also noted. Therefore, the
https://doi.org/10.1016/j.jocn.2020.01.063 0967-5868/Published by Elsevier Ltd.
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
2
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 1. (a, b, c): Computed tomography (CT) images of the reported case on presentation showing an infiltrating lesion in the left thalamus with features suggestive of a highgrade neoplasm. (d): Axial T1-weighted image; (e): Axial T1-weighted image post-contrast administration; (f): Fluid attenuation inversion recovery (FLAIR) image; (g) Apparent Diffusion Coefficient (ADC) map; (h): Coronal T2-weighted image.
patient underwent further imaging with a brain MRI scan. Brain MRI showed mixed signal intensity, heterogeneously enhancing mass centered in the left thalamus and extending to involve the left aspect of the upper brainstem (Figs. 1 and 2). There was also a bilobed peripherally enhancing component with suspected areas of central necrosis and tiny foci of hemosiderin staining. This appearance favored a neoplastic process as the underlying cause. Also, there was a mass effect compressing the posterior third ventricle and proximal cerebral aqueduct with findings concerning for mild obstructive supratentorial hydrocephalus. There was a larger area of surrounding infiltrative T2/FLAIR hyperintensity without associated enhancement likely representing a combination of infiltrative neoplasm and vasogenic edema that extended into the left posterior lentiform white matter in the left aspect of the upper brainstem. At this point, the patient was started on dexamethasone and admitted to the hospital for further management. On further diagnostic workup, the patient underwent chest, abdomen, and pelvis CT scan which revealed no evidence of primary malignancy
or metastatic disease. Stereotactic biopsy was advised to reach a definitive diagnosis. The patient underwent brain biopsy with subsequent histopathological examination was suggestive of glioblastoma (Fig. 3). MGMT promoter methylation, IDH1 and IDH2 mutations were not identified. The final diagnosis was assigned as glioblastoma of the left thalamus (WHO Grade IV glial neoplasm). Over the course of next several months, the patient was followed up by our neuro-oncology team and treated with concurrent chemoradiation followed by further adjuvant temozolomide. 3. Discussion Thalamic aphasia is a language dysfunction associated with lesions exclusively affecting the thalamus (usually the left side). Thalamic aphasia may develop in isolated hemorrhagic and ischemic strokes [7,8]. Less frequently, it was also documented in cases of malignant neoplasms involving the thalamus [9], and neuro-surgical interventions [10]. The clinical presentation of
Fig. 2. MRI (DWI) showing a mild mass effect on the posterior margin of the third ventricle (red arrow). MRI (T1-Post contrast) showing ring-enhancing lesion centered within the dorsal medial left thalamus with central necrosis (green arrow). MRI perfusion is demonstrating heterogeneous peripheral diffusion restriction with intra-lesional hemosiderin staining (yellow arrow).
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
3
Fig. 3. Photomicrographs, Hematoxylin and eosin stain, show histopathology of brain biopsy. (a): Vessels with endothelial proliferation, resulting in ischemia and abundant necrosis; (b): area of necrosis, tumor cell shadowing (dead cells) and gemistocytes (arrow); (c): Focus of residual viable tumor cells (astrocytes); (d): Mitotic figure (arrow).
thalamic aphasia varies, and it can present as global aphasia, expressive aphasia, or transcortical aphasia [8]. The most common presentation is transcortical aphasia; transcortical motor aphasia (hesitant and fragmented speech) or transcortical sensory aphasia (poor comprehension, semantic paraphasias, and echolalia) [8]. The distinguishing characteristic of both transcortical aphasia subtypes and a prominent feature of thalamic aphasia is intact and strongly preserved repetition. Other notable findings may include paraphasias [11]. Thalamic aphasia most commonly presents after lesions affecting the left (dominant) thalamus, but cases of aphasia in rightsided lesions were also noted in left-handed patients [12]. It has been proposed that disconnecting thalamic projections to language-related cortical regions is the underlying mechanism of language deficits associated with thalamic lesions [13]. Fig. 4 shows a schematic diagram of the connections between various thalamic nuclei and corresponding cortical areas. Nevertheless, the exact underlying pathophysiological mechanism for the development of thalamic aphasia is still controversial. Thalamic aphasia was reported in vascular lesions involving all vascular territories supplying the different thalamic nuclei (tuberothalamic, paramedian, inferolateral and posterior choroidal arteries) [14]. However, the occurrence of thalamic aphasia has been reported to be higher following hemorrhage affecting the posterior thalamus (pulvinar) in contrast to infarctions affecting the anterior thalamic circulation via tuberothalamic artery (ventral and anterior nuclei) [15]. For an extended period, the clinical-pathological correlative approach has been adopted to explain thalamus contribution in language functions and to explain the mechanism of aphasia following thalamic lesion. Using this approach, most of the thalamic nuclei have been mentioned to contribute to language functions, most notably
ventral lateral nucleus and pulvinar [15]. However, this approach may lead to inaccurate conclusions especially in cases of thalamic hemorrhage. The attempt to explain the neuropsychological symptoms based on hemorrhage location would be erroneous because the expanding hematoma exerts pressure on the surrounding structures and alter the pattern of symptoms. Recent advances in functional neuroimaging technologies enable more accurate conclusions about the thalamus role in language processing. For example, a tractography study showed that Broca’s area is structurally connected to the thalamus (ventral anterior nucleus and pulvinar) and suggested that this network is involved in language processing [16]. Other functional neuroimaging techniques like functional MRI and magnetoencephalography [17,18]. Regarding thalamic aphasia, one study suggested that aphasia associated with thalamic lesions is consistent with the ‘‘selective engagement model” proposed by Crosson [19,20]. In this model, Crosson et al. proposed that the thalamus monitors, controls and integrates the activity in language-related cortical areas (receptive and expressive). Other linguistic models suggested different roles of the thalamus in language that include word alternatives selection, semantic monitoring, and release of cortically formed responses [21]. It is also worth mentioning here that some studies reported concurrent cortical hypoperfusion in language cortical regions in some cases of thalamic aphasia which may indicate a contribution of cortical dysfunction in the neural basis of the thalamic aphasia [22,23]. Future functional neuroimaging research will be helpful in revealing the whole relationship between the thalamus and language and the specific neural basis of thalamus aphasia. From a clinician point of view, physicians utilize a battery of neuropsychological tests for the comprehensive evaluation of aphasias (spoken language, writing, and reading comprehension).
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
4
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 4. A schematic diagram demonstrating the connection between thalamic nuclei and their corresponding cortical areas.
In 1984, Crosson suggested a set of clinical criteria to assist in the diagnosis of thalamic aphasia [10]. Crosson’s definition included: 1) fluent output with frequent paraphasia (mainly semantic); 2) Jargon (severe paraphasia); 3) less severe deficits in auditory comprehension; 4) intact or minimally impaired repetition. In our case, at least two of the four criteria were present. Besides, right-sided weakness, reading and writing impairment were also observed. The explanation for the right-sided weakness could be the direct involvement of the adjacent internal capsule or mass effect of peri-tumor edema. Brain MRI scans are used to support the diagnosis of GBM. It usually appears as a ring-enhancing lesion (centrally necrotic and peripherally enhancing) although this is not specific. Definitive diagnosis requires stereotactic biopsy or tumor resection after craniotomy. The management and the prognosis of thalamic aphasia largely depend on the underlying cause – hemorrhage, infarction, or tumor. In cases of thalamic hemorrhage, the clinical outcome is affected by the size of hematoma, affected nuclei, and extension to adjacent structures [8,24]. Thalamic aphasia due to vascular lesions may resolve after variable periods of time although persistence of residual language dysfunction is a common outcome that requires serious attention [10]. In our case, glioblastoma multiforme is very difficult to treat, and a combination of surgery, radiotherapy, and other treatment modalities will be necessary. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgment Not applicable. Funding Not applicable. Availability of data and material The data that support the findings and conclusions are included in this published article.
Authors’ contributions MG: concept and design of the study. AS & BB: Drafting and editing of the manuscript. MG: critical revision of the manuscript for important intellectual content, read and approved the final manuscript. Consent for publication Informed consent for publication of this case report and any accompanying images was obtained from the patient. Ethics approval and consent to participate The authors declare that ethics approval was not required for this case report. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jocn.2020.01.063. References [1] Ohgaki H et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res 2004;64(19):6892–9. [2] Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet 2001;68(5):1110–8. [3] Kleihues P, Ohgaki H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1999;1(1):44–51. [4] Hamilton SR et al. The molecular basis of Turcot’s syndrome. N Engl J Med 1995;332(13):839–47. [5] Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA 2013;310(17):1842–50. [6] Stupp R et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352(10):987–96. [7] Tuszynski MH, Petito CK. Ischemic thalamic aphasia with pathologic confirmation. Neurology 1988;38(5):800–2. [8] Kumral E et al. Thalamic hemorrhage. A prospective study of 100 patients. Stroke 1995;26(6):964–70. [9] Roosen N et al. Primary thalamic malignant fibrous histiocytoma of the dominant hemisphere causing severe neuropsychological symptoms. Clin Neuropathol 1989;8(1):16–21. [10] Crosson B. Role of the dominant thalamus in language: a review. Psychol Bull 1984;96(3):491–517. [11] Karussis D, Leker RR, Abramsky O. Cognitive dysfunction following thalamic stroke: a study of 16 cases and review of the literature. J Neurol Sci 2000;172 (1):25–9.
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063
Case report et al. / Journal of Clinical Neuroscience xxx (xxxx) xxx [12] Kirshner HS, Kistler KH. Aphasia after right thalamic hemorrhage. Arch Neurol 1982;39(10):667–9. [13] Nadeau SE, Crosson B. Subcortical aphasia. Brain Lang 1997;58(3):355–402. [14] Llano DA. Functional imaging of the thalamus in language. Brain Lang 2013;126(1):62–72. https://doi.org/10.1016/j.bandl.2012.06.004. [15] Crosson BA. Subcortical functions in language and memory. New York, NY, US: Guilford Press; 1992. [16] Bohsali AA et al. Broca’s area – thalamic connectivity. Brain Lang 2015;141:80–8. [17] David O et al. Dynamic causal modeling of subcortical connectivity of language. J Neurosci 2011;31(7):2712–7. [18] Ketteler D et al. The subcortical role of language processing. High level linguistic features such as ambiguity-resolution and the human brain; an fMRI study. Neuroimage 2008;39(4):2002–9.
5
[19] Crosson B. Subcortical functions in language: a working model. Brain Lang 1985;25(2):257–92. [20] Metz-Lutz MN et al. Language functional neuro-imaging changes following focal left thalamic infarction. NeuroReport 2000;11(13):2907–12. [21] Crosson B et al. Models of subcortical functions in language: current status. J Neurolinguistics 1997;10(4):277–300. [22] Radanovic M, Scaff M. Speech and language disturbances due to subcortical lesions. Brain Lang 2003;84(3):337–52. [23] Sebastian R et al. Aphasia or neglect after thalamic stroke: the various ways they may be related to cortical hypoperfusion. Front Neurol 2014;5(231). [24] Tokgoz S et al. Clinical properties of regional thalamic hemorrhages. J Stroke Cerebrovasc Dis 2013;22(7):1006–12.
Please cite this article as: A. Samara, B. Berry and M. Ghannam, Thalamic aphasia secondary to glioblastoma multiforme, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2020.01.063