Evidence of a developmental cerebello-cerebral disorder

doi:10.1016/j.neuropsychologia.2006.04.028

Neuropsychologia

Volume 44, Issue 12, 2006, Pages 2569-2572

https://doi.org/10.1016/j.neuropsychologia.2006.04.028 Get rights and content

Abstract

The objective of this study was to examine the cognitive and neuroanatomical features of an adolescent with developmental hypoplastic left cerebellum who presented with executive and visuo-spatial deficits, nonverbal learning disabilities and interpersonal difficulties. He underwent a neuropsychological assessment, MRI and diffusion tensor imaging MRI. The neuropsychological impairments were primarily in executive functions, spatial and visual perception, graphomotor skills, arithmetic, social perception and comprehension. Fractional anisotropy, which is measured by diffusion tensor imaging and enables assessment of axonal integrity, was reduced in the right cerebral peduncle and right hemisphere white matter (p < 0.001). Based on the results, we hypothesize that disruption of neural circuits linking the hypoplastic left cerebellum to the right hemisphere may contribute to the evolution of a neurocognitive syndrome with characteristics of the developmental right hemisphere syndrome and suggestive of the cerebellar cognitive-affective syndrome.

Introduction

Lesions in the cerebellum cause cognitive and behavioral deficits in addition to the known perturbations of motor control and specific neurobehavioral profiles have been localized to the site of the cerebellar lesions. Right cerebellar lesions can result in auditory sequential memory and language processing deficits, left cerebellar lesions with spatial and visual sequential memory deficits while vermal lesions may lead to speech, language or behavioral disturbances (Riva & Giorgi, 2000; Scott et al., 2001). The cerebellar cognitive-affective syndrome (CCAS), characterized by impaired executive functions, visuo-spatial and language deficits and personality changes can result from lesions in the lateral hemisphere of the posterior cerebellum or in the vermis (Schmahmann, 2004; Schmahmann & Sherman, 1998).

We present an adolescent with congenital left cerebellar and vermal hypoplasia and a neuropsychological profile characterized primarily by executive and visuo-spatial deficits, nonverbal learning disabilities and interpersonal difficulties. This profile is similar to that of the developmental right hemisphere syndrome (DRHS) and has certain features in common with the CCAS (Gross-Tsur, Shalev, Manor, & Amir, 1995; Schmahmann, 2004).

We speculated that the DRHS symptomatology may result from the cerebellar malformations and/or abnormalities in the neural circuits connecting to the right hemisphere. Since conventional MRI did not delineate structural supratentorial abnormalities, we used diffusion tensor MRI (DTI), a technique that measures the anisotropy of water diffusion. This technique enables assessment of the microstructure of white matter pathways, organization and architecture of white matter fibers and demonstrates pathological white matter conditions (Neil, Miller, Mukherjee, & Huppi, 2002). DTI demonstrated disruption of circuits that link the left cerebellar hemisphere and right cerebrum.

Section snippets

Case report

A 14-year-old boy with ataxic-athetoid cerebral palsy was born to non-consanguineous parents after a normal pregnancy and birth, head circumference 34.5 cm. Visual focusing and tracking appeared late, crawling and first words at 2 years and walking at 9 years. Neuropsychological evaluation at age 10 showed normal language skills, including length of utterance, syntax, vocabulary and comprehension, dysarthric but comprehensible speech, low average intelligence, attention deficit hyperactivity

Neuroimaging

Conventional brain MRI demonstrated severe hypoplasia of the left cerebellar hemisphere, with residual tissue visualized; the right cerebellar hemisphere was normal. The vermis was malformed with only its superior aspect identifiable and mild hypoplasia of the right midbrain and pons (Fig. 1a). T₁ and T₂ weighted images showed normal symmetric cerebral hemispheres and normal sized ventricles with normal myelinization as detected by the gray/white matter contrast (Fig. 1b).

DTI was performed on a

Discussion

Our patient, with congenital hypoplasia of the left cerebellar lobe and vermis, manifests the cognitive and behavioral features of the developmental right hemisphere syndrome (DRHS) as well as certain facets of the CCAS. His case is unique in that it is developmental and its symptomatology was primarily associated with right hemisphere functions, specifically visual-spatial deficits, interpersonal social and behavioral difficulties, dyscalculia, dysgraphia and impaired executive functions such

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They noted impairments in verbal intelligence, auditory sequential memory, and language following resection of right-sided tumors and impaired performance on nonverbal tasks, including tests of spatial and visual sequential memory, as well as impaired prosody, after resection of left cerebellar hemisphere tumors. This observation that language deficits occurred more frequently following right cerebellar lesions, whereas visual–spatial impairments tended to occur with left cerebellar damage, was noted also in other studies (Gottwald et al., 2004; Gross-Tsur et al., 2006; Hokkanen et al., 2006). This is consistent with the crossed connections between the cerebral cortex and the cerebellum and with the findings of domain-specific asymmetry in functional imaging studies of healthy subjects (Stoodley and Schmahmann, 2009b).
The notion that the cerebellum is devoted exclusively to motor control has been replaced by a more sophisticated understanding of its role in neurological function, one that includes cognition and emotion. Early clinical reports, as well as physiological and behavioral studies in animal models, raised the possibility of a nonmotor role for the cerebellum. Anatomical studies demonstrate cerebellar connectivity with the distributed neural circuits linked with autonomic, sensorimotor, vestibular, associative, and limbic/paralimbic brain areas. Identification of the cerebellar cognitive affective syndrome in adults and children underscored the clinical relevance of the role of the cerebellum in cognition and emotion. It opened new avenues of investigation into higher-order deficits that accompany the ataxias and other cerebellar diseases, as well as the contribution of cerebellar dysfunction to neuropsychiatric and neurocognitive disorders. Brain imaging studies have demonstrated the complexity of cerebellar functional topography, revealing a double representation of the sensorimotor cerebellum in the anterior lobe and lobule VIII and a triple cognitive representation in the cerebellar posterior lobe, as well as representation in the cerebellum of the intrinsic connectivity networks identified in the cerebral hemispheres. This paradigm shift in thinking about the cerebellum has been advanced by the theories of dysmetria of thought and the universal cerebellar transform, harmonizing the dual anatomic realities of homogeneously repeating cerebellar cortical microcircuitry set against the heterogeneous and topographically arranged cerebellar connections with extracerebellar structures. This new appreciation of cerebellar incorporation into circuits that subserve cognition and emotion mandates a deeper understanding of the cerebellum by practitioners in behavioral neurology and neuropsychiatry because it impacts the understanding and diagnosis of disorders of emotion and intellect and has potential for novel cerebellar-based approaches to therapy.
The cerebellum and cognition
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They noted impairments in verbal intelligence, auditory sequential memory, and language following right-sided tumors; and deficient non-verbal tasks including spatial and visual sequential memory and impaired prosody after left cerebellar hemisphere tumors. Language deficits occurred more frequently following right cerebellar lesions whereas visual-spatial impairments tended to occur with left cerebellar damage, as noted also in other studies [117,124,133]. This is consistent with the crossed connections with the cerebral cortex, and with the findings of domain-specific asymmetry in functional imaging studies of healthy subjects [75].
What the cerebellum does to sensorimotor and vestibular control, it also does to cognition, emotion, and autonomic function. This hypothesis is based on the theories of dysmetria of thought and the universal cerebellar transform, which hold that the cerebellum maintains behavior around a homeostatic baseline, automatically, without conscious awareness, informed by implicit learning, and performed according to context. Functional topography within the cerebellum facilitates the modulation of distributed networks subserving multiple different functions. The sensorimotor cerebellum is represented in the anterior lobe with a second representation in lobule VIII, and lesions of these areas lead to the cerebellar motor syndrome of ataxia, dysmetria, dysarthria and impaired oculomotor control. The cognitive / limbic cerebellum is in the cerebellar posterior lobe, with current evidence pointing to three separate topographic representations, the nature of which remain to be determined. Posterior lobe lesions result in the cerebellar cognitive affective syndrome (CCAS), the hallmark features of which include deficits in executive function, visual spatial processing, linguistic skills and regulation of affect. The affective dyscontrol manifests in autism spectrum and psychosis spectrum disorders, and disorders of emotional control, attentional control, and social skill set. This report presents an overview of the rapidly growing field of the clinical cognitive neuroscience of the cerebellum. It commences with a brief historical background, then discusses tract tracing experiments in animal models and functional imaging observations in humans that subserve the cerebellar contribution to neurological function. Structure function correlation studies following focal cerebellar lesions in adults and children permit a finer appreciation of the functional topography and nature of the cerebellar motor syndrome, cerebellar vestibular syndrome, and the third cornerstone of clinical ataxiology – the cerebellar cognitive affective syndrome. The ability to detect the CCAS in real time in clinical neurology with a brief and validated scale should make it possible to develop a deeper understanding of the clinical consequences of cerebellar lesions in a wide range of neurological and neuropsychiatric disorders with a link to the cerebellum.
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Treatment is symptomatic and includes physical, occupational, and speech therapy. Neurocognitive outcome is variable ranging from normal cognitive functions to learning disability of differing severity with IQ scores between 60 and 74 [30,31,49]. Involvement of the cerebellar vermis seems to be most often correlated with poor cognitive outcome.
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Prenatal Cerebellar Disruptions: Neuroimaging Spectrum of Findings in Correlation with Likely Mechanisms and Etiologies of Injury
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Cerebellar signs are common and may include truncal and limb ataxia, hypotonia, squint, and head nodding and are usually mild in severity.35,36 Cognitive outcome is variable, ranging from normal cognitive functions to learning disability of differing severity with IQ scores between 60 and 74.34,35,54 Abnormalities of the cerebellar vermis is a predictor of poor cognitive functions.
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This prediction is supported by functional neuroimaging findings that language and spatial functions are lateralized within the cerebellum (see above), and clinical reports that language impairments such as impaired verbal fluency (Akshoomoff et al., 1992; Appollonio et al., 1993; Hassid, 1995; Leggio et al., 1995, 2000; Molinari et al., 1997; Schmahmann and Sherman, 1998; Gasparini et al., 1999; Levisohn et al., 2000; Riva and Giorgi, 2000; Gebhart et al., 2002; Richter et al., 2007b) and agrammatism (Silveri et al., 1994; Zettin et al., 1997; Schmahmann and Sherman, 1998; Marien et al., 2001; Ackermann et al., 2004; Kalashnikova et al., 2005) generally arise following right cerebellar hemisphere lesions. In contrast, visual spatial difficulties are more likely to occur after left cerebellar damage (see Wallesch and Horn, 1990; Fiez et al., 1992; Botez-Marquard et al., 1994; Levisohn et al., 2000; Riva and Giorgi, 2000; Scott et al., 2001; Gebhart et al., 2002; Gottwald et al., 2004; Gross-Tsur et al., 2006; Hokkanen et al., 2006), although these findings are less consistent than the link between the right posterolateral cerebellum and language. The suggestion that language problems are primarily due to motor (articulatory) impairment is not supported by patient studies.
Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.
Pitch discrimination in cerebellar patients: Evidence for a sensory deficit
2009, Brain Research
Citation Excerpt :
Similarly, in higher cognition, such implications have been reported for language and verbal working memory tasks (Fiez, 1996; Desmond and Fiez, 1998; Drepper et al., 1999; Fulbright et al., 1999; Leggio et al., 2000; Marien et al., 2001; Gizewski et al., 2005; Jansen et al., 2005; Justus et al., 2005; Hokkanen et al., 2006), declarative memory (Weis et al., 2004), spatial cognition (Parsons and Fox, 1997; Fink et al., 2000; Hulsmann et al., 2003; Imamizu et al., 2003, 2004; Molinari et al., 2004; Lee et al., 2005), sustained attention (Pardo et al., 1991), and executive function (Grafman and Litvan, 1992; Hallett and Grafman, 1997; Burk et al., 1996; Brandt et al., 2004; Gottwald et al., 2004; Kalashnikova et al., 2005). In addition, there have been corresponding reports concerning development (Malm et al., 1998; Karatekin et al., 2000; Scott et al., 2001; Limperopoulos et al., 2005; Gross-Tsur et al., 2006) and a variety of sensory and cognitive functions related to thirst (Parsons et al., 2000), affect (Damasio et al., 2000; Schmahmann and Caplan, 2006; Schutter and van Honk, 2005; Anderson et al., 2005), music (Griffiths et al., 1999; Parsons, 2003; Gaab et al., 2003), pain intensity (Coghill et al., 1999), and hypercapnia and air hunger (Parsons et al., 2001). Such roles in nonmotor or cognitive processing are also supported by anatomical evidence in monkeys showing indirect cerebellar connectivity, via thalamus, pons, and basal ganglia, with cerebral cortex (for reviews, see, e.g., Ramnani, 2006; Schmahmann and Pandya, 2008; Habas et al., 2009; Strick et al., 2009).
In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

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NoteEvidence of a developmental cerebello-cerebral disorder

Abstract

Introduction

Section snippets

Case report

Neuroimaging

Discussion

Long-term sequelae in children after cerebellar astrocytoma surgery

Neurology

Neuropsychological evaluation of the child

A simplified method to measure diffusion tensor from seven MR images

Magnetic Resonance Medicine

Mind reading difficulties in the siblings of people with Asperger's syndrome: Evidence for a genetic influence in the abnormal development of a specific cognitive domain

Journal of Child Psychology and Psychiatry

Pictures of facial affect

Developmental right hemisphere syndrome: The clinical spectrum of the nonverbal learning disability

Journal of Learning Disabilities

Neuropsychological consequences of cerebellar tumour resection in children. Cerebellar cognitive affective syndrome in a paediatric population

Brain

MRI atlas of human white matter

Note
Evidence of a developmental cerebello-cerebral disorder