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Akinetic Mutism Responsive to Following Subdural Hematoma Evacuation in a Patient With —Case Report—

Myoung Soo KIM, Jong Joo RHEE,SeungJunLEE,Seon-JooKWON*, and Chae Heuck LEE

Departments of Neurosurgery and *Neurology, Seoul Paik Hospital, Inje University College of , Seoul, R.O.K.

Abstract An 11-year-old girl with obstructive hydrocephalus developed akinetic mutism after treatment for hydrocephalus due to aqueductal stenosis by ventriculoperitoneal (VP) shunting. Bilateral chronic sub- dural hematomas developed about 2 months after insertion of the VP shunt and were evacuated. Postoperatively, the patient developed akinetic mutism, but her condition improved after administra- tion of bromocriptine. Absence of abnormalities on transporter single photon emission com- puted tomography, lack of clinical response to levodopa treatment, and normal homovanillic acid con- centration in the cerebrospinal fluid all indicated normal dopamine production. Pressure on the periventricular monoamine projections in the and hypothalamus without major dopamine deprivation in the striatum may have been the most important factors in the development of akinetic mutism in this patient.

Key words: akinetic mutism, hydrocephalus, bromocriptine

Introduction ry of gait disturbance, memory disturbance, and learning difficulty. She was lethargic and had devel- Akinetic mutism is a state in which a seemingly oped slurred speech and urinary incontinence. Com- awake patient remains motionless and silent, and is puted tomography (CT) demonstrated obstructive associated with lesions involving the ascending hydrocephalus (Fig. 1). A ventriculoperitoneal (VP) dopaminergic activating system. Akinetic mutism is shunt with a pressure-adjustable valve (Codman typically a transient disorder following posterior Medos programmable valve, Medos SA, Le Locle,

fossa tumor resection, and may also occur after Switzerland; opening pressure 100 mmH2O) was recurrent shunt failures in patients with hydro- inserted. Subsequently, the patient complained of cephalus, who show no improvement either sponta- intermittent headache. On day 51 after insertion of neously or with shunt revisions but respond to the VP shunt, she was lethargic and complained of bromocriptine.2,4,13,19,24) However, little is known severe headache. CT in the emergency department about the state of dopamine production in the demonstrated a right subdural hematoma (SDH) of patients with akinetic mutism.20) (Fig. 2). Burr hole trephination was performed on We treated a patient with akinetic mutism caused the right. CT obtained 2 days postoperatively by ventricular wall expansion and discuss the in- showed a left SDH (Fig. 3), and further burr hole volvement of dopamine production. trephination was performed on the left. CT per- formed after the burr hole trephinations showed that Case Report the SDHs had almost completely disappeared. After surgery, the patient remained awake, motionless, An 11-year-old girl presented with a 16-month histo- and mute, and she would move all extremities only

Received January 9, 2007; Accepted June 23, 2007 Author's present address: J. J. Rhee, M.D., Department of Neurosurgery, Cheongju Saint Mary's Hospital, Cheongju, R.O.K.

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Fig. 1 Computed tomography scan obtained on Fig. 3 Computed tomography scan obtained at first admission at another hospital demon- follow-up examination 2 days after right strating marked hydrocephalus. burrhole trephination demonstrating left subdural hematoma.

care. We found no signs of rigidity. The VP shunt functioned well, and the opening pressure of the

shunt valve was 110 mmH2O. Electroencephalogra- phy disclosed no epileptic discharge. Magnetic resonance (MR) imaging, including perfusion- weighted and diffusion-weighted MR imaging, showed no abnormal finding except for a small residual SDH and improved hydrocephalus (Fig. 4). 123I-beta-fluoropropyl-2beta-carbomethoxy-3beta-(4- iodophenyl)tropane (123I-FP-CIT)-single photon emission computed tomography (SPECT) demon- strated normal presynaptic dopamine reuptake in the bilateral putamens and caudate nuclei (Fig. 5). The concentration of homovanillic acid (HVA) in the Fig. 2 Computed tomography scan obtained at cerebrospinal fluid was 67.86 ng/ml (normal range follow-up examination 51 days after ven- 1–73 ng/ml). triculoperitoneal shunting showing right Treatment with Madopar , Rapid 125 Tablet (La subdural hematoma. Roche Ltd., Basel, Switzerland) (benserazide 25 mg, levodopa 100 mg) was begun on postoperative day in response to deep pain. The patient showed no 31 after the second burr hole operation, initially improvement despite conservative treatment and 31.25 mg/day and increasing gradually to 187.5 adjustment of the shunt valve opening pressure from mg/day in three equal doses. Despite 12 days of

100 to 140 mmH2O on several occasions (i.e., from Madopar treatment, her symptoms did not improve. 100 to 120 mmH2O, 120 to 140 mmH2O, 140 to 130 We stopped the Madopar administration and began mmH2O, and 130 to 110 mmH2O). She was referred treatment with bromocriptine, initially 1.25 mg/day to our department for evaluation and treatment 30 and increasing gradually to 50 mg/day in three equal days after the left burr hole trephination. doses. Two days after the initiation of bromocriptine Examination on admission revealed features con- administration, she began speaking words and sistent with akinetic mutism. She appeared to be responding to verbal stimuli. Twenty days after the awake but was almost completely unresponsive to initiation, she was speaking in full sentences and her surroundings. She seldom responded to painful demonstrated no gait disturbance, although she had somatosensory, loud auditory, or threatening visual memory disturbance and learning difficulty. Treat- stimuli. Occasionally, she seemed to make spontane- ment with trihexyphenidyl was begun on day 66 ous but weak attempts to move her extremities. She after the second burr hole operation, initially 2 required complete tube feeding and total nursing mg/day and increasing gradually to 6 mg/day in

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Fig. 4 Axial T1-weighted (A), T2-weighted (B), and diffusion-weighted (C) magnetic resonance images obtained at follow-up examination 26 days after burrhole trephination for the left sub- dural hematoma demonstrating improved hydrocephalus and residual subdural hematoma.

forms, depending on its cerebellar or hydrocephalic origin. Injury of the mesiofrontal lobes is the most frequently reported cause of akinetic mutism. One patient had akinetic mutism caused by hemorrhagic infarction of both cingulate gyri,3) and three patients had akinetic mutism caused by anterior cingulate lesions due to bilateral anterior cerebral artery in- farctions.9) Similar symptoms have been associated with anterior cingulate lesions.6,10,25) Animal studies and case reports have identified two primary lesion sites that may be associated with akinetic mutism: the mesencephalic-dien- 123 Fig. 5 I-beta-fluoropropyl-2beta-carbomethoxy- cephalic reticular activating system, including the 3beta-(4-iodophenyl)tropane-single photon reticular formation, thalamus, and emission computed tomography images hypothalamus1,7,12); and the anterior cingulate gyrus demonstrating normal presynaptic dopa- mine reuptake in the bilateral putamens and and adjacent mesial frontal lobes. Lesions at these caudate nuclei. sites occur along pathways that originate in the mesencephalon and project widely to dopamine receptors in the spinal cord, brainstem, diencepha- three equal doses. We did not change the shunt valve lon, corpus striatum, and mesiofrontal lobe.8,18,24) opening pressure during adjustment of the drug The diffuse nonspecific reticular activating system, dose. Seven months after the second burr hole oper- which normally interacts with these specific projec- ation, she had only slight residual dystonia of the tions as a coordinated unit, remains intact. The body and mild memory disturbance. An attempt to resultant behavioral abnormality causes the patient decrease the dosage of bromocriptine 5 months after to remain awake but unable to initiate motor activity initiation because of dyskinesia failed, with rapid in response to sensory stimuli, that is a state of sen- clinical deterioration including decreased spontane- sory inattention. ous speech and motor activity. Return to the previ- Pressure transmitted to the diencephalon from ous dosage of bromocriptine reversed the decline in hydrocephalus or third ventricular tumors can cause symptoms. akinetic mutism.2,4,17,24) The underlying mechanism is believed to be damage to the periventricular Discussion monoamine projections in the thalamus and hypothalamus caused by expansion of the third The clinical features of patients with akinetic ventricular wall.19,22) The degree and duration of mutism associated with hydrocephalus are listed in ventricular wall expansion required to injure the Table 1. Akinetic mutism can appear in different monoamine projection fibers remains unknown, but

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Table 1 Summary of clinical features in patients with akinetic mutism following hydrocephalus (HD) treatment

Age Case Author (Year) (yrs)/ HD Operation Time of onset Treatment No. Sex

1 Berger et al. 21/F obstructive HD multiple shunt after 3rd shunt shunt revision, (1985)4) due to AS operation due to operation cogentin, shunt malfunction DOPA/benserazide (prolopa) 2 Watahiki et al. 39/M obstructive HD multiple shunt after 3rd shunt levodopa, (1987)24) due to AS operation due to operation bromocriptine, shunt malfunction trihexyphenidyl 3Anderson 20/M obstructive HD multiple shunt after 4th shunt bromocriptine, (1992)2) due to AS operation due to operation ephedrine shunt malfunction 4 Lee et al. 34/M unilateral multiple shunt after 3rd shunt bromocriptine (2002)13) ventricle HD operation due to operation shunt malfunction 5 Psarros et al. 26/F obstructive HD endoscopic exploration, immediately bromocriptine (2003)19) due to cyst resection, after cystic mass septostomy operation

AS: aqueductal stenosis.

lesioning of these structures in animals induces lesion, which affects the substantia nigra.2) akinetic mutism, which can be reversed with dopa- HVA concentration was normal in the cerebrospi- mine .23) This observation forms the basis of nal fluid of a patient with akinetic mutism caused by dopamine use in humans with akinetic hypothalamic damage.20) However, the dopamine mutism.20) A patient with akinetic mutism caused by metabolism is unclear in patients with akinetic hydrocephalus was treated successfully with levodo- mutism resulting from hydrocephalus. Some pa- pa, bromocriptine, and trihexyphenidyl.24) Another tients with chronic hydrocephalus may experience patient with akinetic mutism resulting from obstruc- decreased autoregulatory capacity for cerebral tive hydrocephalus was treated with bromocriptine blood volume. In our patient, this mechanism was and ephedrine.2) excluded by perfusion-weighted MR imaging, which The causative damage may be maximal in regions revealed no perfusion changes.11) Our patient did not adjacent to the third ventricle.5) This region contains respond to Madopar, a presynaptic dopamine- monoaminergic projection fibers from the brain mimetic drug, so we thought that the medial fore- stem.21,23) Akinetic mutism does not result from brain bundles were probably destroyed. Therefore, simple elevation of intracranial pressure,5) which is we decided to try treatment with direct dopamine consistent with clinical observations of patients agonists based on the results of animal experiments with pseudotumor cerebri, who can experience and a previous case report.14,15) pronounced elevation of intracranial pressure In our patient, the clinical and pharmacologic without becoming mute. Akinetic mutism also does evidence indicated that the lesion predominantly not result from simple dilation of the cerebroven- involved the periventricular monoamine projections tricular system. A review of previous cases revealed in the thalamus and hypothalamus, more specifical- that the syndrome usually develops after multiple ly the presynaptic dopamine axons coursing in the shunt revisions for shunt failure.4,16,24) This observa- anterior portions of the medial forebrain bundles. tion suggests that the brain undergoes a series of The unresponsiveness of this patient to Madopar stretching and contraction cycles, so the repeated coupled with the initial response to low-dose cycles of ventricular dilation and relaxation may dopamine agonists suggest that the presynaptic somehow alter the physical characteristics and catecholaminergic mechanisms were inoperative. result in more rapid dilation in response to in- On the other hand, if our patient's lesion had creased intracerebral pressure, which exceeds the involved the anterior cingulate gyri, she probably speed of compensatory mechanisms and results would not have responded to direct dopamine in damage.2) Such stretching might occur in the agonists because the dopamine receptor targets midbrain structures or the nigrostriatal system, and would have been destroyed.20) The absence of abnor- might lead to dysregulation of this system without malities on 123I-FP-CIT-SPECT (dopamine transport- major dopamine deprivation through the midbrain er SPECT), lack of clinical response to levodopa

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