Unusual association of diseases/symptoms CASE REPORT Acquired stuttering due to recurrent anaplastic astrocytoma Katherine B Peters,1 Scott Turner2 1 Departments of Neurology and Surgery, Duke University Medical Center, Durham, North Carolina, USA 2 Department of Neurosurgery, Geisinger Medical Center, Danville, Pennsylvania, USA Correspondence to Dr Katherine B Peters, katherine.peters@duke.edu SUMMARY Acquired (neurogenic) stuttering is a rare phenomenon seen after cerebral infarction or brain injury. Aetiology of this symptom is unclear, but recent evidence supports that it is a disturbance in the left hemispheric neural network involving the interplay between the cortex and basal ganglia. We present the case of a patient who develops acquired stuttering after a recurrence of a right temporoparietal anaplastic astrocytoma (WHO grade III). We also review other cases of acquired stuttering and known anatomical correlates. BACKGROUND To cite: Peters KB, Turner S. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2013009562 Stuttering is a disruption of verbal fluency with involuntary repetition or prolongation of sounds or syllables. There may be silent or audible pauses which can be accompanied by anxiety or secondary motor symptoms such as facial grimacing. Stuttering is not a diagnosis, but a symptom, the exact aetiologies of which are unclear. To better understand this condition, stuttering has been categorised as developmental or neurogenic depending on its onset and characteristics. Developmental stuttering typically presents before puberty, often as early as 2–5 years of age with a male predominance and without apparent neurological injury. The incidence of developmental stuttering is approximately 5% with an estimated overall recovery rate of 74%, leading to a prevalence of 1% in adults.1 Developmental stuttering tends to be more common at the beginning of words and is usually associated with secondary symptoms. Developmental stuttering exhibits both adaptation, (it occurs less frequently with repeated attempts) and consistency (it occurs with the same words or syllables).2 Neurogenic or acquired stuttering is much less common and occurs following known brain injury. It may exhibit a slow onset when associated with degenerative diseases such as Parkinson’s disease or it may appear suddenly following stroke or trauma. Stuttering has also been associated with certain medications, including tricyclic antidepressants and phenothiazines.3–7 Helm et al8 described five characteristics of neurogenic stuttering that distinguish it from developmental stuttering: (1) lack of adaptation; (2) repetitions, prolongations and blocks are not restricted to initial syllables; (3) stuttering occurs on small grammatical words as well as substantive words; (4) absence of anxiety; and (5) rarely occurs with secondary motor symptoms such as facial grimacing. Peters KB, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-009562 Although rare, acquired stuttering has been reported in the setting of acute stroke in a number of patients (table 1). Infarcts in all lobes and in dominant as well as non-dominant hemispheres have been described.8–17 Though the mechanism remains unclear, stuttering has been attributed to lesions in the supplementary motor area, pons, putamen, the left and right parietal lobes, the thalamus and the corpus callosum.18–21 Using voxelbased lesion-symptom correlates, Theys et al22 showed that acquired stuttering from infarcts is not due to one specific lesion but rather a dysfunction in the left-sided neural network compromised of the cortex-basal ganglia-cortex. Infarcts as well as tumours have been used through the years to map important regions of the brain in order understand better the mechanisms of speech and language. There have been several reports of infarcts leading to stuttering and here, we present a first case report of recurrent anaplastic astrocytoma leading to acquired stuttering which correlated temporally with the tumour’s extension into the right parietal lobe and across the corpus callosum. CASE PRESENTATION A patient with a history of hypertension was evaluated for a left visual field deficit. This was the only abnormality detected on the patient’s neurological examination at the time of MRI. MRI with and without gadolinium revealed a diffusely abnormal signal involving the right temporoparietal region. A stereotactic biopsy confirmed the diagnosis of anaplastic astrocytoma (WHO grade III) and he received 5940 cGy of radiation therapy along with concurrent oral temozolomide. After combined treatment, MRI was read as stable disease and the patient then received two cycles of adjuvant temozolomide dosed at 150 mg/m2 for 5 days in 28-day cycle. After the completion of two cycles of 5-day temozolomide, the patient presented to the Preston Robert Tisch Brain Tumour Center at Duke with a worsening left visual field deficit and new onset of intermittent stuttering. An MRI at that time showed progressive disease consisting of a diffusely enhancing mass involving the right splenium of the corpus callosum, which extended to the left side and into the right temporal lobe, basal ganglia and occipital lobe (figure 1). The patient was then started on irinotecan in combination with bevacizumab. On neurological examination, the patient was alert and oriented to person, place and time. The patient scored a 28/30 on the Mini-Mental State Examination and only missed points for interlocking pentagon task and lack of recall of one memory 1 Unusual association of diseases/symptoms Table 1 Reports on acquired stuttering associated with neurological injury Reference Age (years) Handedness Gender Fleet and Heilman13 Ardila and Lopez10 Soroker et al17 Abe et al18 Kono et al23 Grant et al14 Grant et al14 Grant et al14 Grant et al14 Tsumoto et al24 Ciabarra et al25 Ciabarra et al25 Ciabarra et al25 Hagiwara et al26 Turgut et al27 Doi et al28 Kakishita et al19 Fawcett12 Hamano et al29 Sahin et al30 Sahin et al30 Osawa et al31 Tani and Sakai32 Tani and Sakai33 Tani and Sakai33 Tani and Sakai33 Tani and Sakai33 Tani and Sakai33 42 50 65 38 54 68 59 59 55 66 53 54 63 52 61 60 51 84 77 65 95 51 45 49 16 50 8 77 Right Right Right Not Reported Not Reported Right Right Ambidextrous Right Right Right Right Left Right Right Not Reported Right Left Right Right Right Right Right Ambidextrous Right Right Right Right Female Male Male Male Male Male Male Male Male Male Male Female Female Male Male Male Male Female Female Female Male Male Male Male Male Male Female Male Lesion Cerebral infarction Cerebral Infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infaction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Cerebral infarction Brain haemorrhage Traumatic brain injury Cerebral infarction Brain haemorrhage due to arteriovenous malformation Cerebral infarction word. The patient did admit to mild prosopagnosia. On speech evaluation, the patient had evidence of stuttering. Repetition, comprehension and naming were all normal and intact. As for fluency, the patient could form sentences appropriately but would stutter over multiple words. The patient continued to have a left homonymous hemianopsia. Motor strength was normal. The patient was hyperreflexic on the left side with 3+. There was a mild reduction of temperature sensation in the left upper and left lower extremities in comparison to the right side. The patient’s gait was mildly unsteady because the patient had difficulty in looking to the left per the patient. A general physical examination was unremarkable. Figure 1 Fluid-attenuated inversion recovery (A) and T1 with gadolinium (B) showing involvement of the right parietal lobe and splenium of the corpus callosum. 2 Right frontoparietal Right temporal Right hemisphere, post capsule/putamen Paramedian thalami and midbrain Left basal ganglia Left frontotemporal Left posterior temporal/bilateral cerebellum Right parietal Left medial occipital Corpus callosum: body, splenium Left rostromedial pons Left putamen, caudate, corona radiata Left corona radiata and left lateral putamen Corpus callosum: body, splenium Left parietal Midbrain, upper pons Corpus callosum: genu, anterior body Left basal ganglia Corpus callosum: body Left parietal-supramarginal gyrus, angular gyrus Left supramarginal gyrus Left parietal, occipital, and temporal Right cerebellum Left putamen Right pons, right and left putamen Bilateral basal ganglia and left pons Left parietal Bilateral putamen OUTCOME AND FOLLOW-UP Throughout the patient’s treatment course, the patient continued to experience stuttering. After completing 2 years of treatment on bevacizumab-containing regimens, the patient passed away in hospice. DISCUSSION Although stuttering has been described for centuries, its underlying causes remain unclear. On average, children who stutter exhibit slightly delayed speech development and have a slightly higher than average incidence of behavioural disorders, suggesting a possible cognitive component,34 though results are not conclusive. Studies linking stuttering to dystonic contractions of muscles that affect speech have not been borne out, but the fact that antidopaminergic agents such as haloperidol, olanzapine and risperidone have proven helpful in treating stuttering suggest an overactivity of dopaminergic neurons, possibly in the basal ganglia, may play a role.4 Neuroimaging and electroencephalography analysis have not demonstrated a single area of abnormality in the brains of stutterers, but functional neuroimaging has demonstrated hyperactivity in the right hemisphere in stutterers as well as a problem with coordination between the left frontal and left central cortex. Moreover, positron emission tomography studies have shown abnormal hemispheric dominance with activation of the left hemisphere during stuttered speech and a possible compensatory hyperactivity of the right hemisphere during fluent speech.35 36 Peters KB, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-009562 Unusual association of diseases/symptoms Attempts to localise regions that regulate fluent speech by analysing brains of patients who developed acquired stuttering following a stroke have failed to show a consistent location or pattern that leads to stuttering. Neurogenic stutterers, in fact, have lesions in both hemispheres and in all lobes.2 Our case involved a patient who developed stuttering with tumour involvement of the corpus callosum, suggesting that this structure may play a role in producing fluent speech. In addition to this case, there have been five cases of infarct of the corpus callosum that caused stuttering. All five involved the body to some extent and three involved the splenium.19 Three of the five developed a callosal apraxia, though that was not the case with our patient. Friederici et al37 compared the speech patterns of patients who had infarcts throughout the corpus callosum to those of normal controls and concluded that the posterior third of the corpus callosum, including the splenium, is involved in processing prosodic information and syntax. In the case presented here, the patient had a known right-sided anaplastic astrocytoma that caused a homonymous hemianopsia. As the tumour extended into the right temporal lobe and into the left hemisphere through the corpus callosum, he developed intermittent stuttering. However, callosal infarcts have been reported previously without causing stuttering or other speech disorders, while infarcts throughout the cortex and brainstem have led to stuttering in a number of cases. Speech fluency, therefore, is difficult to localise to one area, but rather depends on the interplay between various parts of the cortex, requiring interhemispheric communication through the corpus callosum. Two separate case reports in the central nervous system literature have examined stuttering. Seki et al38 described a recurrence of developmental stuttering from a brain tumour in the corpus callosum. In a separate report, Balamurali et al39 describe a case of improvement of persistent developmental stuttering after surgical excision of a left perisylvian meningioma. In these case reports, the stuttering was developmental rather than acquired and in left perisylvian meningioma case report, the stuttering improved after the removal of the tumour. Our case report represents with first description of acquired stuttering due to brain tumour recurrence. 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Learning points ▸ Acquired stuttering is rare neurological phenomenon that can occur as a result of acute neurological injury. ▸ Ischaemic stroke is a well-documented aetiology of acquired stuttering. ▸ This case report demonstrates the first description of acquired stuttering due to brain tumour recurrence. 28 29 30 31 32 33 34 Contributors KBP and ST are responsible for the conception and design, drafting, analysis and final approval of the version to be published. 35 Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed. REFERENCES 1 2 3 Yairi E, Ambrose NG. Early childhood stuttering I: persistency and recovery rates. J Speech Lang Hear Res 1999;42:1097–112. Buchel C, Sommer M. What causes stuttering? PLoS Biol 2004;2:E46.. 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