Authors: Masahiro Hatakeyama, Midori Watanabe, Shin Koide, Hiromi Hashida, Tomone Taneda, Natsuki Akiyama, Takayoshi Tokutake, Masato Kanazawa, Osamu Onodera
Categories: Case Report, Aphasia, Brainstem infarction, Cerebellar cognitive affective syndrome, Cortico-ponto-cerebellar pathway
Source: Cerebellum (London, England)
Authors: Masahiro Hatakeyama, Midori Watanabe, Shin Koide, Hiromi Hashida, Tomone Taneda, Natsuki Akiyama, Takayoshi Tokutake, Masato Kanazawa, Osamu Onodera
Cognitive impairment resulting from cerebellar damage, known as cerebellar cognitive affective syndrome (CCAS), can cause language impairment and aphasia. The disruption of the cerebro-cerebellar pathway is a possible mechanism for CCAS. Consequently, aphasia may also arise from brainstem lesions. However, the precise mechanisms of brainstem-induced aphasia are not fully understood owing to the scarcity of published reports describing this condition. Herein, we investigated characteristics of patients with aphasia attributed to the brainstem infarction. We retrospectively analyzed medical records of 24 patients with brainstem infarction, two of whom presented with aphasia. The first patient was a 64-year-old, right-handed Japanese man who developed word-finding difficulties and verbal paraphasia. The second patient was an 85-year-old, right-handed Japanese woman who developed auditory verbal comprehension impairment, word-finding difficulties, and verbal paraphasia. Both patients had an infarction of the left ventral part of the upper pons on magnetic resonance imaging scans. Next, we illustrated language-related cerebellar afferent and efferent fibers using HCP-1065 Young Adult Fiber Template. The afferent pathway, which projected from the Broca area to the right Crus I and II through the cortico-ponto-cerebellar pathway, descended to the pons and decussated contralaterally at the ventral part of the upper pons, the area affected by the lesions common to our two cases. The efferent pathway (dentate-rubro-thalamic tract) was located away from these lesions. An infarction of the left ventral part of the upper pons may disrupt the language-related cerebellar afferent pathway, which likely caused word-finding impairments in our two patients.
The cerebellum is known to play a role in coordinating movement and regulate cognitive and behavioral functions. Cognitive impairment resulting from cerebellar damage, known as cerebellar cognitive affective syndrome (CCAS), is characterized by deficits in executive function, visuospatial cognition, affect regulation, and language abilities [1]. The cerebellum is involved in motor speech production, verbal fluency, grammatical/syntactical processing, reading, writing, metalinguistic skills, and verbal working memory [2]. In addition, cases of aphasia caused by cerebellar lesions have also been reported [2, 3]. Symptoms observed in cerebellar-induced aphasia include word-finding difficulties, expressive and receptive agrammatism, reduced verbal fluency, as well as reading and writing deficits [2]. The disruption of connections between the cerebellum and cerebral cortices is a possible mechanism for CCAS. Consequently, aphasia may also arise from brainstem lesions [4].
The cerebellum is linked to the cerebral hemispheres via afferent and efferent pathways. The right Crus I and Crus II have been reported to be related to language function [5] and receive input projections from cerebral language area through the cortico-ponto-cerebellar pathway [6]. The dentate-rubro-thalamic tract is known as the cerebellar efferent pathway [7]. These cerebro-cerebellar connections have also been described in primates. For example, by using neuron tracing, Schmahmann et al. showed that the cortico-pontine pathway originates from the prefrontal cortices in the rhesus macaques, and hypothesized that these projections are relevant for the cognitive function of the cerebellum [8]. Therefore, the disruption of the afferent and/or efferent cerebellar pathways may contribute to brainstem-induced aphasia. However, the precise mechanisms of brainstem-induced aphasia are not fully understood owing to the scarcity of published reports describing this condition [9, 10]. Herein, we conducted a retrospective study to clarify the pathophysiology of brainstem-induced aphasia by identifying common symptoms and lesions attributed to the brainstem infarction in patients with aphasia.
We performed a retrospective analysis of medical records of consecutive patients with brainstem infarction, who were admitted to our hospital between April 2020 and March 2023. Aphasia was assessed by a neurologist (M.H.) or speech-language-hearing therapist (H.H.) experienced in the evaluation of this condition. We excluded patients with infarction in the left cerebral hemisphere from the analysis. We investigated common symptoms and lesions in patients with brainstem-induced aphasia.
In addition, to illustrate the language-related cerebro-cerebellar pathways, we performed fiber tracking using DSI Studio software (http://dsi-studio.labsolver.org/) with Human Connectome Project (HCP)-1065 Young Adult Fiber Template (https://brain.labsolver.org/). The afferent pathway included the fibers projecting from the Broca area to the right Crus I and Crus II via the corticopontine tract. The efferent pathway comprised fibers projecting from the right dentate nucleus to the left red nucleus. All anatomical structures were delineated according to the atlas preinstalled in DSI Studio.
The Institutional Review Board of the Niigata University Medical & Dental Hospital (Niigata, Japan) approved this study (approval No. 2024 − 0305), which was conducted in accordance with the Declaration of Helsinki.
Of the 24 patients with brainstem infarction, two presented with aphasia. The detailed clinical findings were as follows.
The first patient was a 64-year-old, right-handed Japanese man with a history of hypertension, diabetes mellitus, and schizophrenia. The patient was admitted to our hospital because he had difficulty moving his right upper and lower limbs. Upon admission, dysarthria and incomplete paralysis of the right upper and lower limbs were observed. Brain magnetic resonance imaging (MRI) on admission revealed an infarction in the left ventral part of the upper pons (Fig. 1a, b). Brain magnetic resonance angiography (MRA) showed no significant findings except for hypoplasia of the right vertebral artery (Fig. 1c). Initial language evaluations were performed 4–8 days after admission using the Standard Language Test for Aphasia (SLTA) [11]. The patient was alert and cooperative. Dysarthria was observed in spontaneous speech, whereas apraxia of speech and phonemic paraphasia were absent. Auditory verbal comprehension was not impaired; however, in the object naming task, word-finding difficulties and verbal paraphasia (e.g., mistaking “desk” for “chair”) were noted (the score for the SLTA object naming task was 13 [normal 19.6 ± 0.8]). In the second language evaluation performed 36 days after admission, word-finding difficulties improved (the score on the object-naming task of SLTA was 18).
Fig. 1Radiological features of the two aphasia cases. (a, b) Magnetic resonance imaging (MRI) of the first patient. Fluid-attenuated inversion recovery imaging (a) and diffusion-weighted imaging (b) showed infarction of the left ventral part of the upper pons. (c) Brain magnetic resonance angiography (MRA) of the first patient showed no significant findings except for hypoplasia of the right vertebral artery. (d, e) MRI of the second patient. Fluid-attenuated inversion recovery imaging (d) and diffusion-weighted imaging (e) showed infarction that extended from the ventral part of the pons to the midbrain bilaterally. Scattered small infarcts in the bilateral cerebellar hemisphere were also observed. (f) Brain MRA of the second patient showed no significant findings except for hypoplasia of the right vertebral artery. (g) Lesion common to the two patients (pink area). (h, i) Cerebellar afferent (h) and efferent (i) pathways depicted using DSI Studio software with Human Connectome Project (HCP)-1065 Young Adult Fiber Template
The second patient was an 85-year-old, right-handed Japanese woman with a history of chronic kidney disease, liver dysfunction, and hyperuricemia. The patient was transferred to our hospital because of the disturbance of consciousness. On admission, spontaneous speech was lacking, and incomplete tetraplegia was observed. Brain MRI taken 3 days after admission showed an infarction extending bilaterally from the ventral part of the pons to the midbrain, corresponding to the basilar artery territory. Small infarcts were also observed bilaterally in the cerebellar hemispheres (Fig. 1d, e). Brain MRA showed no significant findings except for hypoplasia of the right vertebral artery (Fig. 1f). After admission, the patient’s spontaneous speech gradually recovered. Detailed language evaluations were performed 14–20 days after admission using the Japanese version of the Western Aphasia Battery [12]. The patient was alert and cooperative. Her speech was slurred, scanning, and explosive, but apraxia of speech and phonemic paraphasia were not observed. Auditory verbal comprehension was impaired at the single-word level. In the object naming task, word-finding difficulties and verbal paraphasia (e.g., mistaking “stamp” for “clock”) were noted (the scores of the single-word comprehension task and object naming task of Western Aphasia Battery were 33 [normal 59.9 ± 1.3] and 53 [normal 59.2 ± 2.4], respectively).
Both patients had an infarction of the left ventral part of the upper pons (Fig. 1g). Next, we compared the location of these lesions with the locations of the language-related cerebellar efferent and afferent pathways. The cerebellar afferent pathway descended to the pons and decussated contralaterally at the ventral part of the upper pons, where the lesions common to our two cases exited (Fig. 1h), whereas the cerebellar efferent pathway was located away from these lesions (Fig. 1i).
In this study, we found that both our patients commonly developed word-finding impairments and had an infarction of the left ventral part of the upper pons, although small infarcts in the right cerebellar hemisphere may also have contributed to the aphasia in the second patient.
The effects of brainstem lesions on the language ability have not been investigated in detail. For example, Shimmyo et al. reported a case series of nine patients with pontine stroke who developed cognitive dysfunction; however, they only assessed verbal fluency and did not conduct detailed assessment of aphasia [13]. In previous reports, three cases with aphasia caused by isolated brainstem insult have been reported. Hoffmann et al. reported a patient with bilateral pontine infarction, who developed word-finding impairments [9]. Garrard et al. reported a patient with hemorrhage into the midbrain and upper pons and a patient with left-side pontine infarction, both of whom developed word-finding impairments [10]. Therefore, the common aphasia symptom in the previous reports is word-finding impairment, which is consistent with observations in our two patients.
Regarding the pathophysiology of cognitive impairment due to brainstem lesion, two hypotheses have been disruption of the monoaminergic nuclei in the brainstem [14] and diaschisis [13, 15]. The lesion common to our two cases was located away from the monoaminergic nuclei in the brainstem, such as substantia nigra, raphe nucleus, and locus coeruleus, and overlapped with the cerebellar afferent pathway. Therefore, we hypothesized that diaschisis was the main cause of clinical signs in these two patients. Diaschisis can occur both anteriorly and posteriorly relative to the lesion. Pontine infarctions can cause hypoperfusion of both the cerebral cortices and cerebellum [16]. Thus, we speculated that pontine lesions decreased the activity in the cerebral cortices and cerebellum by disrupting the cerebellar afferent pathway in our patients. The language-related cerebellar afferent pathway originates from several cerebral cortices, including the Broca area, which is responsible for word-finding abilities [6, 17]. Therefore, disruption of the cerebellar afferent pathway may have caused word-finding difficulties in our patients.
Notably, the symptoms of the first patient improved within several weeks after the onset of pontine infarction. Language-related networks are reported to change dramatically following brain damage. Activation of the cerebral cortices distant from the lesion site can be observed in patients with aphasia, which may be a sign of functional recovery [18]. We also reported a patient who developed aphasia due to cerebellar hemorrhage following the recovery from aphasia due to left parietal infarction, and hypothesized that the cerebellum compensated for the latter impairment [3]. Therefore, it is possible that other language-related networks compensated for the disruption of the cerebellar afferent pathway leading to the recovery of aphasia in our first patient. Supporting this point, functional connectivity within the cerebrum is reported to change after the pontine infarction [16]. Thus, it is imperative that future research using functional imaging investigates the networks related to the functional recovery following brainstem-induced aphasia.
The current study has several limitations. First, this study included only two patients with brainstem-induced aphasia. Thus, to classify brainstem lesions responsible for aphasia, systematic investigations including a larger number of patients should be conducted in the future. Second, this was a retrospective study, so we did not perform detailed language evaluation of all the patients. The number of patients presenting with similar aphasia may be larger than what is apparent in this study. Third, in contrast to findings in our two patients, distinct brainstem lesions cause other types of language impairment, such as mutism owing to the disruption of the cerebellar efferent pathway [7] and word deafness owing to the inferior colliculi lesion [19]. Therefore, language impairments may depend on the lesion location, and each such impairment should be examined using a larger number of cases.
An infarction of the left ventral part of the upper pons may disrupt the language-related cerebellar afferent pathway and cause word-finding impairments.