Nonsurgical cerebellar mutism (anarthria) in two children

Introduction 

Mutism is a general descriptive term describing total absence of speech in an awake and conscious patient [1]. It can reflect aphasia, anarthria (caused by paralysis of the speech apparatus), or aphonia (caused by laryngeal disease). It can also be a manifestation of behavioral disturbance known as (s)elective mutism in which children are shy, have a tendency to avoid others, or are even withdrawn. Cerebellar mutism is a form of severe dysarthria marked by profound impairment of fluency, articulation, and modulation of speech [2], that is, anarthria. Mutism occurs primarily in children [1], [3], [4] and occasionally in adults [5] as a well-recognized complication of posterior fossa surgery. It is often associated with a particular behavior characterized by irritability and disturbances in socialization and communication ranging from emotional lability to autistic withdrawal [6], [7], [8]. However, postoperative mutism differs from elective mutism because, in the latter, children have normal verbal communication with selected people or in selected contexts.

Nonsurgical cases of cerebellar mutism have been rarely reported [9], [10]. They are primarily traumatic in origin [3], [5]. We discuss two children who developed anarthria and a behavior similar to that described in postoperative mutism, one child with cerebellar involvement caused by hemolytic–uremic syndrome and the other with postinfectious cerebellitis.

Patient 1 

A 5-year-old female presented with generalized tonic–clonic seizures and a 2-day history of bloody diarrhea. On admission she was pyrexial (39°C), obtunded, and in hypovolemic shock (systolic blood pressure, 60 mm Hg; thready pulse of 150/minute). After resuscitation, her level of consciousness improved. Two days later, she developed thrombocytopenia, disseminated intravascular coagulation, and acute renal failure that required hemodialysis. On examination, she manifested generalized hypotonia, dysarthria, dysmetria, action tremor, and ataxic gait. The results of an electroencephalogram (EEG) test were normal. Cerebral magnetic resonance imaging (MRI) obtained the following day revealed diffuse hyperintensity of the cerebellar cortex on fluid attenuated inversion recovery sequence. Three days later, bloody diarrhea recurred. Abdominal ultrasound and colonoscopy indicated pancolitis. Failure of conservative treatment led to surgical resection a week after recurrence of her diarrhea. Pathologic examination revealed hemorrhagic rectocolitis with disseminated ulcerated lesions. Results of a stool examination were negative for Escherichia coli 0157:H7 toxin.

After extubation on the third postoperative day, she was withdrawn but able to make sounds. After several hours, she stopped vocalizing. Receptive language seemed intact with no deficit in single-word recognition. She could follow simple verbal commands. Voluntary tongue movements and swallowing were normal. There was no cranial nerve palsy. Upper-extremity dysmetria and truncal ataxia were present without limb weakness. She was aloof, even toward her parents. Repeat EEG results were normal. On the tenth postoperative day she uttered single ill-articulated words. MRI performed on the twentieth postoperative day revealed moderate cortical and subcortical atrophy with no abnormal signal in the cerebellar cortex. Throughout the next days, her language improved but remained agrammatic. She was unable to sequence symbolic activities and actions. Considerable slowness typified her performance of simple tasks. Gradual improvement in communication skills was associated with her behavior returning to normal. On the twenty-sixth postoperative day, she became acutely unwell, exhibiting generalized edema and tachycardia caused by pericardial effusion and panmyocarditis. Cardiogenic shock and hypotension were refractory to medical treatment and pericardial tap, necessitating extracorporeal membrane oxygenation. She died 48 hours later after massive pulmonary hemorrhage.

Postmortem neuropathologic examination indicated signs of cerebral edema with severe meningeal congestion and hemorrhages and signs of cerebral tentorial herniation. Serial sectioning of the brain revealed massive fresh hemorrhages in both ventricles and various telencephalic, diencephalic, and brainstem regions, including the cerebellum. Microscopic findings demonstrated signs of disseminated intravascular coagulation in small cerebral vessels. The cerebellum manifested signs of previous ischemic insult, namely, ischemic cerebellar cortical sclerosis with total loss of Purkinje cells and marked loss of neurons in the granular layer (Fig 1A) as compared with normal age-matched control (Fig 1B). These findings indicate two distinct processes: early cerebellar ischemia likely concomitant with abnormal speech and behavior, and late (fatal) hemorrhage involving the whole brain. Major systemic findings included diffuse thrombotic microangiopathy involving kidneys, heart, and liver, with evidence of disseminated intravascular coagulation and thrombotic events within small blood vessels. The clinical finding combining acute microangiopathic nonautoimmune hemolytic anemia, thrombocytopenia, and acute renal failure with histopathologic findings involving microcirculation is consistent with severe postcolitis hemolytic–uremic syndrome.

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Figure 1. Histologic examination of cerebellar cortex. (A) Postmortem neuropathologic examination of Patient 1, conducted by using Cresyl Violet (Nissl) staining, reveals marked loss of granular and Purkinje cells with a spongiform neuropil, indicating ischemic cerebellar cortical necrosis. Microthrombus is evident in a small blood vessel. (B) Normal cerebellar cortex from an age-matched child for comparison.

Patient 2 

A 4-year-old female presented with a 3-day history of right leg pain, anorexia, and general apathy. On the day of admission, she vomited several times and was noted to have a vacant stare. She was withdrawn. Initial whimpering noises became inconsolable whining that lasted several hours. On examination, she was apyrexial and manifested incoherent and dysarthric speech, upper limb dysmetria, and ataxic gait. Pupillary reactions to light were normal. There was no nystagmus. Diagnostic evaluation revealed normal findings on blood biochemistry and hemogram tests, blood and urine toxicology screening, cerebrospinal fluid examination (protein level, 0.21 g/L; glucose, 51 mg/dL, two lymphocytes), and cerebral computed tomography. EEG revealed diffuse excess of slow activity without asymmetry. She received erythromycin and intravenous acyclovir and ceftriaxone. She remained apyrexial and manifested persistent vomiting and no improvement in consciousness level. A second lumbar puncture 48 hours later revealed a raised protein level (0.81 g/L) and white cell count (720 cells with 96% neutrophils) and normal glucose level (63 mg/dL). Viral polymerase chain reaction (PCR) and viral culture of cerebrospinal fluid manifested no herpes simplex virus, herpes zoster virus, Epstein-Barr virus, parvovirus B19, or enteroviruses. Serology results were also negative.

MRI 48 hours after admission demonstrated cerebellar swelling (Fig 2A) with hyperintensity of cerebellar cortex on T2-weighted fluid attenuated inversion recovery sequence (Fig 2B). Two weeks later, cerebellar atrophy and hyperintensity of deep cerebellar cortex were observed on T2-weighted fluid attenuated inversion recovery sequence MRI scans (Fig 2C). Single-photon emission computerized tomogram using Hexamethyl propene amino oxine (HMPAO) performed a month later revealed diffuse perfusion anomalies in the cerebellum and no cerebral abnormalities. Three weeks after admission, she started speaking single words with dysarthria and was able to walk unaided. Speech recovery was gradual and was characterized by word-finding difficulties and slow language processing. On follow-up 6 months later, she had difficulties processing and integrating visuospatial information. A year later, she is in mainstream school with weekly speech and language therapy.

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Figure 2. Magnetic resonance imaging (MRI) evolution in Patient 2. (A) T1-weighted axial MRI scan (TR, 550 ms; TE, 10 ms) indicating cerebellar tumefaction with smoothing of gyral pattern and poor identification of cerebellar folia. (B) Hyperintensity of cerebellar cortex with normal supratentorial parenchyma on T2-weighted coronal fluid attenuated inversion recovery sequence (TR, 6000 ms; TE, 150 ms; TI, 2000 ms). The arrow indicates the direction of phase encoding. (C) Abnormal deep cortico-cerebellar hyperintensity with cerebellar atrophy on T2-weighted coronal fluid attenuated inversion recovery sequence.

Discussion 

We describe two children who developed transient cerebellar mutism (anarthria) accompanied by a characteristic behavior associated with ischemic cerebellar infarction caused by hemolytic–uremic syndrome in one child and cerebellitis in the other. In both children, anarthria was followed by dysarthria.

Most reported cases of cerebellar mutism occurred after surgery for posterior fossa tumor [3], [4], [7] or cerebellar hemorrhage [1], [3], [5]. Postoperative mutism is classically transient [1], [3], [4], [7], with lack of cranial nerve dysfunction and long-tract signs [1], [2], [11]. Comprehension remains unaffected. A period of intact speech usually occurs and lasts from a few hours to several days [4], [5], [12] after surgery. Speech recovery occurs after a variable period [3], [4]. Although unable to speak, patients often exhibit some degree of whining or crying [7], [12]. The two children we describe presented a behavioral pattern similar to that in postoperative mutism.

The few nonsurgical reports are essentially traumatic in origin. An infectious etiology has been reported in a 4-year-old female who developed transient cerebellar anarthria in the course of pneumococcal meningitis [10]. Another 4-year-old girl with cerebellitis developed anarthria after ventriculoperitoneal shunt insertion [9].

In a previous reported pediatric case of fatal postcolitis hemolytic–uremic syndrome with cerebellar involvement, pathologic examination revealed vascular damage and microinfarcts confined to the cerebellum, findings similar to those for Patient 1 and an animal model of hemolytic–uremic syndrome [13]. However, this patient did not exhibit anarthria.

The cerebellum is part of a network of cerebello–cerebral/cerebrocerebellar connections that process and mediate complex social and cognitive behaviors [6], [8], [14]. Cerebellar cognitive affective syndrome, well described in adults, consists of poverty of initiation and decreased verbal fluency, sometimes to the point of mutism [15]. This finding is similar to the behavioral pattern observed in Patients 1 and 2 and children with postoperative mutism: emotional lability, apathy, lack of initiative, and inattention [6], [7], [11]. As in postoperative mutism, language recovery and gradual normalization of the behavior of Patients 1 and 2 were simultaneous.

The anatomic basis for speech disturbances in postoperative mutism remains conjectural. Various mechanisms have been proposed, including impaired vascular supply possibly secondary to vasospasm [2], bilateral edema within the brachium pontis [7], splitting of vermis [5], involvement of dentatothalamic tract [3], [4], [8], [11], trauma to left cerebellar hemisphere [1,3], and development of hydrocephalus [3], [4]. The contribution of cerebral cortical involvement is difficult to evaluate. In Patient 1, it could be supported by microscopic findings of disseminated intravascular coagulation and involvement of small cerebral vessels. Diaschisis of cerebello–frontal connections has also been suggested as causing loss of higher cerebral function [8], [9], which is supported by functional studies in postsurgical mutism that indicate cerebral hypoperfusion [16]. Functional imaging in Patient 2, however, did not reveal supratentorial hypoperfusion, which is in accordance with findings of other studies [7]. An integrative hypothesis explains postoperative mutism as possible impairment of neural pathway(s) at any one of a number of sites within the posterior fossa rather than in a single region or specific pathway [7]. Pathologic findings from the first patient are consistent with this hypothesis.

These case reports add to the experience of cerebellar anarthria syndrome extending outside the context of posterior fossa surgery or trauma and support a role of the cerebellum as modulator of communication and social functions [6], [15].