- Split View
-
Views
-
Cite
Cite
Jürgen Konczak, Beate Schoch, Albena Dimitrova, Elke Gizewski, Dagmar Timmann, Functional recovery of children and adolescents after cerebellar tumour resection, Brain, Volume 128, Issue 6, June 2005, Pages 1428–1441, https://doi.org/10.1093/brain/awh385
- Share Icon Share
Abstract
This study examined whether lesions to the cerebellum obtained in early childhood are better compensated than lesions in middle childhood or adolescence. Since cerebellar lesions might affect motor as well a cognitive performance, posture, upper limb and working memory function were assessed in 22 patients after resection of a cerebellar tumour (age at surgery 1–17 years, minimum 3 years post-surgery). Working memory was only impaired in those patients who had received chemo- or radiation therapy. Postural sway was enhanced in 64% of the patients during dynamic posturography conditions, which relied heavily on vestibular input for equilibrium control. Upper limb function was generally less impaired, but 54% of the patients revealed prolonged deceleration times in an arm pointing task, which probably does not reflect a genuine cerebellar deficit but rather the patients' adopted strategy to avoid overshooting. Age at surgery, time since surgery or lesion volume were poor predictors of motor or cognitive recovery. Brain imaging analysis revealed that lesions of all eight patients with abnormal posture who did not receive chemo- and/or radiation therapy included the fastigial and interposed nuclei (NF and NI). In patients with normal posture, NI and NF were spared. In 11 out of 12 patients with abnormal deceleration time, the region with the highest overlap included the NI and NF and dorsomedial portions of the dentate nuclei in 10 out of 12 patients. We conclude that cerebellar damage inflicted at a young age is not necessarily better compensated. The lesion site is critical for motor recovery, and lesions affecting the deep cerebellar nuclei are not fully compensated at any developmental age in humans.
Introduction
Brain damage interferes with normal development and this may involve delayed maturation of structure and abnormal function resulting from deficient or aberrant connectivities. Historically, it was thought that children were well suited to cope with brain damage, since their immature brains were believed to possess a high degree of plasticity. In support of this view were reports that lesions in the cortex or in subcortical regions such as the cerebellum experienced at a young age had less effect on later functioning than similar lesions occurring later in life (Little, 1862; O'Donoghue et al., 1986). However, with respect to the cerebellum, the findings of other studies suggest that the relationship between recovery from injury and age is not necessarily linear, but needs to account for the type of cerebellar function and the localization of the cerebellar lesion (Dennis et al., 1996, 1999). Animal studies have shown that recovery from lesions to the deep nuclei of the cerebellum is often less complete, even if the lesions were obtained shortly after birth (Botterell and Fulton, 1938a, b; Eckmiller and Westheimer, 1983). Yet, extrapolating from animal data to humans is not without problems, given their differences in neuroanatomy and behaviour (Gramsbergen, 1993; Matano, 1986, 2001). Also, the effect of an acute lesion in a previously intact animal is probably different from the effect of a human lesion after tumour resection, considering that a tumour might trigger compensatory brain processes well before surgery. At this point, we observe a dearth of systematic clinical studies that examined the recovery of function after a cerebellar lesion during human development.
It is established that the cerebellum of humans and non-human primates follows a mediolateral organization, effectively dividing the cerebellar cortex and the underlying deep nuclei into three functional zones (Jansen and Brodal, 1940). The vermis and nuclei fastigii (NF) form the most medial zone, which is mainly concerned with the control of posture and locomotion. Damage of the medial zone in humans and the inactivation of the NF in monkeys lead to problems in sitting, standing and walking (Dichgans and Mauritz, 1983; Thach et al., 1992; Bastian et al., 1998).
The intermediate zone consists of the nucleus interpositus (NI; in humans: n. emboliformis and n. globosus) and those portions of the paravermal cortex that project to these nuclei. In its original conception, the NI were thought to be the only nuclei of this zone (Jansen and Brodal, 1940). However, newer neuroanatomical evidence revealed that adjacent dorsomedial regions of the dentate nucleus exhibit similar properties and may also be part of the intermediate zone. Temporary inactivation of the NI and the adjacent portion of the dentate nucleus in monkeys causes tremor (Thach et al., 1992) and impairments in reaching and grasping gestures (Growdon et al., 1967; Mackel, 1987; Mason et al., 1998).
The lateral cerebellar hemisphere and most of the dentate nucleus form the lateral cerebellar zone. Its anterior portion is said to be involved in motor control, while the posterolateral portion is believed to participate in motor planning, language production and cognitive processes such as memory function (Leiner et al, 1993; Middleton and Strick, 1998; Dum et al., 2002). Working memory deficits after cerebellar lesions have been reported both in some children and in adults (Schmahmann and Sherman, 1997; Levisohn et al., 2000).
In the past, several studies examined how cerebellar lesions are compensated during human development. Dennis et al. (1999) reported no relationship between cerebellar motor function and age at lesion onset. Levinsohn et al. (2000) concluded that the age at surgery and lesion site influence the neurobehavioural outcome. In contrast, other studies revealed little or no influence of age on cognitive functions (Hetherington et al., 2000; Riva and Giorgi, 2000; Scott et al., 2001; Steinlin et al., 2003).
Given that motor and possibly cognitive function are functionally compartmentalized within the human cerebellum, no systematic and comprehensive study has examined the link between lesion site, development and the restitution of function. This study seeks to fill this knowledge gap by studying cognitive and motor performance of children, adolescents and young adults after the resection of a cerebellar tumour. Specifically, we examined working memory, postural control and upper limb function. We sought to answer two questions: (i) is recovery accelerated or improved if the damage to the cerebellum occurs early in development? (ii) how does recovery depend on the site of the lesion?
Subjects and methods
Subjects
A total of 22 cerebellar patients (age range 10–28 years) and 14 healthy controls (age range 11–28 years) participated in the study. In all patients, a cerebellar tumour had been removed surgically in the past. The first group had surgery within the first 4 years of life (early childhood), a second middle childhood group had surgery between the ages of 6 and 9 years and a third adolescent group had surgery between the ages of 12 and 17 years. School education was comparable between the three groups. At the time of testing, patients were at least 3 years post-surgery. The mean duration after surgery was 8.2 years. Each subject was examined by an experienced neurologist (D.T.) and rated according to the International Cooperative Ataxia Rating Scale of the World Federation of Neurology (WFN scale) (Trouillas et al., 1997). A detailed description of the patient characteristics including tumour type, adjuvant therapies and clinical examination scores is given in Table 1.
ID . | Age (years) . | Age at surgery (years) . | Developmental age . | Tumour . | Chemotherapy . | Radiation . | Shunt . | Vermal split . | WFN total (max. 100) . | WFN gait and posture (max. 34) . | WFN upper limb (max. 36) . | WFN kinetic (max. 52) . | WFN speech (max. 8) . | WFN oculomotor (max. 6) . | Handedness . |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A.B. | 10 | 3 | Early | Medulloblastoma | Yes | Unknown | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
C.S. | 11 | 6 | Mid | Astrocytoma, I. | No | 6.0 | 1.5 | 4.5 | 4.5 | 0.0 | 0.0 | L (R) | |||
C.D. | 15 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
D.H. | 18 | 15 | Adolesc | Astrocytoma, II. | Yes | 2.0 | 0.0 | 2.0 | 0.0 | 0.0 | 0.0 | R | |||
D.K | 13 | 8 | Mid | Astrocytoma, I. | Yes | 8.0 | 3.0 | 4.0 | 4.0 | 0.0 | 1.0 | R | |||
E.S. | 13 | 2 | Early | Medulloblastoma | Yes | Yes | Yes | 6.5 | 2.5 | 4.0 | 4.0 | 0.0 | 0.0 | R | |
H.W. | 10 | 4 | Early | Astrocytoma, I. | Unknown | 9.5 | 2.5 | 4.5 | 7.0 | 0.0 | 0.0 | R | |||
H.S. | 15 | 9 | Mid | Medulloblastoma | Yes | Yes | Yes | 15.5 | 2.0 | 10.0 | 11.0 | 0.0 | 3.5 | R | |
J.R. | 16 | 13 | Adolesc | Astrocytoma, I. | No | 19.0 | 4.0 | 9.0 | 11.5 | 0.0 | 3.5 | L (R) | |||
J.B. | 11 | 7 | Mid | Ependymoma, III. | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
J.O. | 20 | 9 | Mid | Astrocytoma, I. | Yes | 9.5 | 4.5 | 5.0 | 5.0 | 0.0 | 0.0 | R (L) | |||
M.M | 21 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
M.S. | 15 | 3 | Early | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
N.K. | 17 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.B. | 18 | 12 | Adolesc | Cavernoma | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.U. | 20 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 1.5 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
S.D. | 28 | 17 | Adolesc | Astrocytoma, I. | No | 1.0 | 1.0 | 0.0 | 0.0 | 0.0 | 0.0 | L | |||
S.S. | 13 | 6 | Mid | Astrocytoma, I. | Yes | Yes | 9.0 | 3.5 | 5.0 | 5.0 | 0.0 | 0.5 | R | ||
S.A. | 18 | 1 | Early | Plexuspapilloma | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
S.R. | 15 | 8 | Mid | Medulloblastoma | Yes | Yes | Unknown | 5.5 | 5.5 | 0.0 | 1.0 | 0.0 | 0.0 | R | |
W.S | 21 | 8 | Mid | Medulloblastoma | Yes | Yes | Yes | No | 6.0 | 0.5 | 4.5 | 4.5 | 0.0 | 1.0 | R |
Y.M. | 28 | 13 | adolesc | Astrocytoma, I. | Yes | Yes | 15.0 | 4.0 | 7.5 | 10.0 | 1.0 | 0.0 | R |
ID . | Age (years) . | Age at surgery (years) . | Developmental age . | Tumour . | Chemotherapy . | Radiation . | Shunt . | Vermal split . | WFN total (max. 100) . | WFN gait and posture (max. 34) . | WFN upper limb (max. 36) . | WFN kinetic (max. 52) . | WFN speech (max. 8) . | WFN oculomotor (max. 6) . | Handedness . |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A.B. | 10 | 3 | Early | Medulloblastoma | Yes | Unknown | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
C.S. | 11 | 6 | Mid | Astrocytoma, I. | No | 6.0 | 1.5 | 4.5 | 4.5 | 0.0 | 0.0 | L (R) | |||
C.D. | 15 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
D.H. | 18 | 15 | Adolesc | Astrocytoma, II. | Yes | 2.0 | 0.0 | 2.0 | 0.0 | 0.0 | 0.0 | R | |||
D.K | 13 | 8 | Mid | Astrocytoma, I. | Yes | 8.0 | 3.0 | 4.0 | 4.0 | 0.0 | 1.0 | R | |||
E.S. | 13 | 2 | Early | Medulloblastoma | Yes | Yes | Yes | 6.5 | 2.5 | 4.0 | 4.0 | 0.0 | 0.0 | R | |
H.W. | 10 | 4 | Early | Astrocytoma, I. | Unknown | 9.5 | 2.5 | 4.5 | 7.0 | 0.0 | 0.0 | R | |||
H.S. | 15 | 9 | Mid | Medulloblastoma | Yes | Yes | Yes | 15.5 | 2.0 | 10.0 | 11.0 | 0.0 | 3.5 | R | |
J.R. | 16 | 13 | Adolesc | Astrocytoma, I. | No | 19.0 | 4.0 | 9.0 | 11.5 | 0.0 | 3.5 | L (R) | |||
J.B. | 11 | 7 | Mid | Ependymoma, III. | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
J.O. | 20 | 9 | Mid | Astrocytoma, I. | Yes | 9.5 | 4.5 | 5.0 | 5.0 | 0.0 | 0.0 | R (L) | |||
M.M | 21 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
M.S. | 15 | 3 | Early | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
N.K. | 17 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.B. | 18 | 12 | Adolesc | Cavernoma | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.U. | 20 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 1.5 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
S.D. | 28 | 17 | Adolesc | Astrocytoma, I. | No | 1.0 | 1.0 | 0.0 | 0.0 | 0.0 | 0.0 | L | |||
S.S. | 13 | 6 | Mid | Astrocytoma, I. | Yes | Yes | 9.0 | 3.5 | 5.0 | 5.0 | 0.0 | 0.5 | R | ||
S.A. | 18 | 1 | Early | Plexuspapilloma | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
S.R. | 15 | 8 | Mid | Medulloblastoma | Yes | Yes | Unknown | 5.5 | 5.5 | 0.0 | 1.0 | 0.0 | 0.0 | R | |
W.S | 21 | 8 | Mid | Medulloblastoma | Yes | Yes | Yes | No | 6.0 | 0.5 | 4.5 | 4.5 | 0.0 | 1.0 | R |
Y.M. | 28 | 13 | adolesc | Astrocytoma, I. | Yes | Yes | 15.0 | 4.0 | 7.5 | 10.0 | 1.0 | 0.0 | R |
Developmental age: early = early childhood; mid = middle childhood; adolesc = adolescence. Vermal split: cerebellar vermis was split during neurosurgery; unknown = surgical records were not explicit; WFN = World Federation of Neurology ataxia score; WFN upper limb = subset of WFN kinetics that only relates to arm function; R and L = the dominant hand prior to surgery.
ID . | Age (years) . | Age at surgery (years) . | Developmental age . | Tumour . | Chemotherapy . | Radiation . | Shunt . | Vermal split . | WFN total (max. 100) . | WFN gait and posture (max. 34) . | WFN upper limb (max. 36) . | WFN kinetic (max. 52) . | WFN speech (max. 8) . | WFN oculomotor (max. 6) . | Handedness . |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A.B. | 10 | 3 | Early | Medulloblastoma | Yes | Unknown | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
C.S. | 11 | 6 | Mid | Astrocytoma, I. | No | 6.0 | 1.5 | 4.5 | 4.5 | 0.0 | 0.0 | L (R) | |||
C.D. | 15 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
D.H. | 18 | 15 | Adolesc | Astrocytoma, II. | Yes | 2.0 | 0.0 | 2.0 | 0.0 | 0.0 | 0.0 | R | |||
D.K | 13 | 8 | Mid | Astrocytoma, I. | Yes | 8.0 | 3.0 | 4.0 | 4.0 | 0.0 | 1.0 | R | |||
E.S. | 13 | 2 | Early | Medulloblastoma | Yes | Yes | Yes | 6.5 | 2.5 | 4.0 | 4.0 | 0.0 | 0.0 | R | |
H.W. | 10 | 4 | Early | Astrocytoma, I. | Unknown | 9.5 | 2.5 | 4.5 | 7.0 | 0.0 | 0.0 | R | |||
H.S. | 15 | 9 | Mid | Medulloblastoma | Yes | Yes | Yes | 15.5 | 2.0 | 10.0 | 11.0 | 0.0 | 3.5 | R | |
J.R. | 16 | 13 | Adolesc | Astrocytoma, I. | No | 19.0 | 4.0 | 9.0 | 11.5 | 0.0 | 3.5 | L (R) | |||
J.B. | 11 | 7 | Mid | Ependymoma, III. | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
J.O. | 20 | 9 | Mid | Astrocytoma, I. | Yes | 9.5 | 4.5 | 5.0 | 5.0 | 0.0 | 0.0 | R (L) | |||
M.M | 21 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
M.S. | 15 | 3 | Early | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
N.K. | 17 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.B. | 18 | 12 | Adolesc | Cavernoma | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.U. | 20 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 1.5 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
S.D. | 28 | 17 | Adolesc | Astrocytoma, I. | No | 1.0 | 1.0 | 0.0 | 0.0 | 0.0 | 0.0 | L | |||
S.S. | 13 | 6 | Mid | Astrocytoma, I. | Yes | Yes | 9.0 | 3.5 | 5.0 | 5.0 | 0.0 | 0.5 | R | ||
S.A. | 18 | 1 | Early | Plexuspapilloma | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
S.R. | 15 | 8 | Mid | Medulloblastoma | Yes | Yes | Unknown | 5.5 | 5.5 | 0.0 | 1.0 | 0.0 | 0.0 | R | |
W.S | 21 | 8 | Mid | Medulloblastoma | Yes | Yes | Yes | No | 6.0 | 0.5 | 4.5 | 4.5 | 0.0 | 1.0 | R |
Y.M. | 28 | 13 | adolesc | Astrocytoma, I. | Yes | Yes | 15.0 | 4.0 | 7.5 | 10.0 | 1.0 | 0.0 | R |
ID . | Age (years) . | Age at surgery (years) . | Developmental age . | Tumour . | Chemotherapy . | Radiation . | Shunt . | Vermal split . | WFN total (max. 100) . | WFN gait and posture (max. 34) . | WFN upper limb (max. 36) . | WFN kinetic (max. 52) . | WFN speech (max. 8) . | WFN oculomotor (max. 6) . | Handedness . |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
A.B. | 10 | 3 | Early | Medulloblastoma | Yes | Unknown | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
C.S. | 11 | 6 | Mid | Astrocytoma, I. | No | 6.0 | 1.5 | 4.5 | 4.5 | 0.0 | 0.0 | L (R) | |||
C.D. | 15 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
D.H. | 18 | 15 | Adolesc | Astrocytoma, II. | Yes | 2.0 | 0.0 | 2.0 | 0.0 | 0.0 | 0.0 | R | |||
D.K | 13 | 8 | Mid | Astrocytoma, I. | Yes | 8.0 | 3.0 | 4.0 | 4.0 | 0.0 | 1.0 | R | |||
E.S. | 13 | 2 | Early | Medulloblastoma | Yes | Yes | Yes | 6.5 | 2.5 | 4.0 | 4.0 | 0.0 | 0.0 | R | |
H.W. | 10 | 4 | Early | Astrocytoma, I. | Unknown | 9.5 | 2.5 | 4.5 | 7.0 | 0.0 | 0.0 | R | |||
H.S. | 15 | 9 | Mid | Medulloblastoma | Yes | Yes | Yes | 15.5 | 2.0 | 10.0 | 11.0 | 0.0 | 3.5 | R | |
J.R. | 16 | 13 | Adolesc | Astrocytoma, I. | No | 19.0 | 4.0 | 9.0 | 11.5 | 0.0 | 3.5 | L (R) | |||
J.B. | 11 | 7 | Mid | Ependymoma, III. | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
J.O. | 20 | 9 | Mid | Astrocytoma, I. | Yes | 9.5 | 4.5 | 5.0 | 5.0 | 0.0 | 0.0 | R (L) | |||
M.M | 21 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 2.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
M.S. | 15 | 3 | Early | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
N.K. | 17 | 8 | Mid | Astrocytoma, I. | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.B. | 18 | 12 | Adolesc | Cavernoma | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | |||
P.U. | 20 | 13 | Adolesc | Medulloblastoma | Yes | Yes | Yes | 2.0 | 1.5 | 0.0 | 0.0 | 0.0 | 0.0 | R | |
S.D. | 28 | 17 | Adolesc | Astrocytoma, I. | No | 1.0 | 1.0 | 0.0 | 0.0 | 0.0 | 0.0 | L | |||
S.S. | 13 | 6 | Mid | Astrocytoma, I. | Yes | Yes | 9.0 | 3.5 | 5.0 | 5.0 | 0.0 | 0.5 | R | ||
S.A. | 18 | 1 | Early | Plexuspapilloma | Yes | No | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | R | ||
S.R. | 15 | 8 | Mid | Medulloblastoma | Yes | Yes | Unknown | 5.5 | 5.5 | 0.0 | 1.0 | 0.0 | 0.0 | R | |
W.S | 21 | 8 | Mid | Medulloblastoma | Yes | Yes | Yes | No | 6.0 | 0.5 | 4.5 | 4.5 | 0.0 | 1.0 | R |
Y.M. | 28 | 13 | adolesc | Astrocytoma, I. | Yes | Yes | 15.0 | 4.0 | 7.5 | 10.0 | 1.0 | 0.0 | R |
Developmental age: early = early childhood; mid = middle childhood; adolesc = adolescence. Vermal split: cerebellar vermis was split during neurosurgery; unknown = surgical records were not explicit; WFN = World Federation of Neurology ataxia score; WFN upper limb = subset of WFN kinetics that only relates to arm function; R and L = the dominant hand prior to surgery.
Motor testing procedures
We assessed postural stability using dynamic posturography. Subjects stood on a force platform (NeuroCom Inc., Portland, OR). Ground reaction forces were recorded and the motion of the platform or the visual surround could be coupled online to a patient's anterior–posterior sway. We will use the term sway-referenced to refer to the test condition, where such coupling took place. The test was designed to examine static and dynamic balance under different sensory conditions and consisted of 18 separate trials. In each trial, ground reaction forces were recorded for a duration of 20 s at a sampling frequency of 100 Hz. Prior to testing, subjects were instructed simply to stand still and to keep their balance for the duration of a trial. Stepping off the platform was coded as a ‘fall’. To prevent injury during falling, participants wore a harness that was attached to an overhead support beam. The conditions of each trial are listed in Table 2.
Visual surround . | Platform . | Trials . | Testing goal is to determine . |
---|---|---|---|
Stable | Stable | 1–3 | Balance function under normal sensory conditions |
Eyes closed | Stable | 4–6 | Dependency on vision |
Sway-referenced | Stable | 7–9 | Sensitivity to loss of posture-relevant visual information |
Stable | Sway-referenced | 10–12 | Sensitivity to loss of posture-relevant proprioceptive information |
Eyes closed | Sway-referenced | 13–15 | Dependency on vestibular sense |
Sway-referenced | Sway-referenced | 16–18 | Dependency on vestibular sense when vision does not provide posture-relevant information |
Visual surround . | Platform . | Trials . | Testing goal is to determine . |
---|---|---|---|
Stable | Stable | 1–3 | Balance function under normal sensory conditions |
Eyes closed | Stable | 4–6 | Dependency on vision |
Sway-referenced | Stable | 7–9 | Sensitivity to loss of posture-relevant visual information |
Stable | Sway-referenced | 10–12 | Sensitivity to loss of posture-relevant proprioceptive information |
Eyes closed | Sway-referenced | 13–15 | Dependency on vestibular sense |
Sway-referenced | Sway-referenced | 16–18 | Dependency on vestibular sense when vision does not provide posture-relevant information |
The term sway-referenced refers to anterior–posterior motion of the visual surround or the platform that is coupled to the person's own sway.
Visual surround . | Platform . | Trials . | Testing goal is to determine . |
---|---|---|---|
Stable | Stable | 1–3 | Balance function under normal sensory conditions |
Eyes closed | Stable | 4–6 | Dependency on vision |
Sway-referenced | Stable | 7–9 | Sensitivity to loss of posture-relevant visual information |
Stable | Sway-referenced | 10–12 | Sensitivity to loss of posture-relevant proprioceptive information |
Eyes closed | Sway-referenced | 13–15 | Dependency on vestibular sense |
Sway-referenced | Sway-referenced | 16–18 | Dependency on vestibular sense when vision does not provide posture-relevant information |
Visual surround . | Platform . | Trials . | Testing goal is to determine . |
---|---|---|---|
Stable | Stable | 1–3 | Balance function under normal sensory conditions |
Eyes closed | Stable | 4–6 | Dependency on vision |
Sway-referenced | Stable | 7–9 | Sensitivity to loss of posture-relevant visual information |
Stable | Sway-referenced | 10–12 | Sensitivity to loss of posture-relevant proprioceptive information |
Eyes closed | Sway-referenced | 13–15 | Dependency on vestibular sense |
Sway-referenced | Sway-referenced | 16–18 | Dependency on vestibular sense when vision does not provide posture-relevant information |
The term sway-referenced refers to anterior–posterior motion of the visual surround or the platform that is coupled to the person's own sway.
Upper limb function was tested in two separate tests—pointing with the index finger (single-joint task) and pointing with the whole arm (multi-joint task). During pointing with the index finger, subjects performed horizontal 45° flexion movements to a visually specified target zone. Start position was a neutral position (0°), where the index finger pointed straight ahead. Since the range of motion of the metacarpal joint exceeds well over 45° and no mechanical stop was in place, subjects had to break the movement actively. Such active breaking implies that over- or undershooting the target (intention tremor) was possible to record. The target itself was a 3 mm wide paper strip attached to a half-arc-shaped metal fence, ∼2–3 cm away from the finger tip. Prior to testing, the hand rested on a table and hand and wrist were fixated by two small metal boards, effectively allowing only motion around the metacarpal joint of the index finger. Movements were recorded with an ultrasound-based motion analysis system (CM20, Zebris GmbH, Tübingen, Germany). Markers were attached to the base (metacarpal joint) and the tip of the index finger. A third stationary marker was placed on the table as a reference marker. The sampling frequency of the ultrasound system was 100 Hz.
In the second task, subjects performed three-dimensional pointing movements with the whole arm to a target at eye height. At the beginning of each trial, the hand rested on a table. These pointing movements had a sizeable vertical and sagittal component (30–40 cm, depending on individual anthropometrics) and primarily involved rotations around the shoulder and elbow joint. The target was positioned at ∼85% of total arm length. Translation of the trunk to aid pointing was prevented and monitored by the experimenter. Trials involving trunk translations were repeated. In each task, both arms were tested. Participants performed a total of 10 trials per arm and task. They were instructed to move quickly and to halt motion at the target location. Active breaking of the hand was emphasized. In order to overcome movement strategies that seek to avoid injury due to overshooting, the target was padded and suspended in the air by four strings attached to ceiling and table. The effect of hitting the target was demonstrated (oscillation of the target) and subjects were allowed to perform several practice trials before testing.
Kinematic measures
The postural test system recorded data of the four force transducers and the associated shear forces between the two force plates. With customized software based on MATLAB technical programming language, the raw data were calibrated and subsequently filtered off-line using a 4th order lowpass Butterworth filter with a cut-off frequency of 3 Hz. Based on the filtered force time data of each 20 s trial, we computed total sway area of the centre of gravity, and length of the sway path for the duration of the trial using algorithms provided by the platform manufacturer (Equitest System Operator's Manual Vers. 4.0, pp. F3–F11). Because all subjects were kept naive with respect to the mechanics of the platform, the unexpected platform tilting in the sway-referenced condition evoked postural reactions in some subjects (forward parachute) during the initial seconds of trial 10 (first trial with a platform tilt). Such reactions were not seen in subsequent trials. These trials were not removed from the analysis, because they occurred in both groups. However, in order to remove any bias in postural sway resulting from the novelty of the situation, we computed the median of sway area and sway path length.
For the assessment of upper limb function, the recorded time position data were filtered offline using a 4th-order lowpass Butterworth filter with a cut-off frequency of 8 Hz. Subsequently, hand and finger velocity and acceleration were calculated separately in each spatial dimension using a three-point differentiation technique. Hand and finger kinematics were based on the motions of a marker attached to the metacarpal joint and a marker placed at the tip of the index finger, respectively. Sagittal and horizontal higher order kinematics were used to compute the resultant two-dimensional velocity and acceleration of the finger movement during the pointing task. For the arm movements, the vertical component was added to compute resultant three-dimensional hand velocity and acceleration. Movement onset and movement end were determined for each pointing movement. Movement onset was defined as the point in time when from the resting position the resultant velocity began to exceed 5% of the movement's peak resultant velocity. Movement end was defined as the point in time when the resultant velocity dropped to 5% of the peak resultant velocity after peak velocity was reached. Acceleration time was defined as the time between movement onset and peak resultant velocity; deceleration time was the time between peak resultant velocity and movement end. For statistical comparisons, we computed the mean for each kinematic variable (deceleration and acceleration time, peak resultant velocity and acceleration) over the 10 recorded movements.
Memory span testing procedures and measures
In order to assess the function of the visuospatial and verbal working memory, we applied Corsi's block tapping task (Orsini, 1994; Orsini et al., 1986) and Wechsler's forward and backward digit span test (Wechsler, 1987) on the same day when behavioural testing was conducted. In the block tapping task, nine identical black cubes (2.5 × 2.5 × 2.5 cm) were arranged irregularly on a small board (20 × 25 cm). The examiner taps a certain number of cubes in a specified sequence, and the participant is required to tap the same pattern immediately afterwards in either the forward or backward fashion. The test began with a sequence of two taps. If a participant failed to reproduce a given sequence, the experimenter moved to the next sequence. Testing was aborted after a subject failed to reproduce three successive sequences. The test score was the number of sequences correctly reproduced. In the digit memory span test, the examiner read aloud a sequence of numbers, which the participant had to repeat immediately afterwards. During reading, the time interval between different digits did not exceed 1 s. The test score was the number of sequences correctly reproduced. The simplest sequence contained three digits, the longest eight digits. The test contained two different sequences at each level (i.e. two three-digit, two four-digit sequences, etc.).
Imaging procedures and measures
In cerebellar patients, the extent of surgical lesions was defined by individual three-dimensional MRI data sets acquired on the same day that behavioural testing was performed. A 3D sagittal volume of the entire brain was acquired using a T1-weighted MPRAGE sequence [field of view (FOV) = 256 mm, number of partitions = 160, voxel size = 1.00 × 1.00 × 1.00 mm3, repetition time (TR)/echo time (TE) = 2400/4.38 ms, flip angle = 8°] on a Siemens Sonata 1.5 T MR scanner. In addition, axial and sagittal 2D T2-weighted images of the entire brain were acquired.
Surgical lesions were traced manually on axial, sagittal and coronal slices of the non-normalized 3D MRI data set and saved as a region of interest using MRIcro software (http://www.mricro.com). The individual volume of the lesion and complete 3D MRI data set were simultaneously spatially normalized into a standard proportional stereotaxic space Montreal Neurological Institute (MNI) 152-space] using SPM99 (http://www.fil.ion.ucl.ac.uk/spm/). The MPRAGE volume was registered and resampled to 2.00 × 2.00 × 2.00 mm3 voxel size.
Because the process of spatial normalization is likely to introduce some errors in individual anatomy particularly within the posterior fossa (Crivello et al., 2002; Salmond et al., 2002), the extent of individual lesions was also analysed based on non-normalized data for each individual subject using characteristic anatomical landmarks. In particular, a possible effect on the cerebellar nuclei was verified by visual inspection of non-normalized scans. Normalized regions of interest were manually adjusted, if the normalization introduced spatial errors that would lead to incorrect localizations. The researcher (B.S.) conducting the MRI analysis was unaware of the behavioural data.
Based on the MNI spatial coordinates of cerebellar lesions, the corresponding cerebellar lobules were defined with the help of 3D MRI atlases of the cerebellum (Schmahmann et al., 2000) and the cerebellar nuclei (Dimitrova et al., 2002). Lesions of vermis, paravermis and lateral hemispheres were considered separately (Schoch et al., 2004).
We used MRIcro software to calculate the volumes of corrected normalized individual lesions. For superimposition of the individual stereotaxically normalized cerebellar lesions, right-sided lesions were flipped to the left. The localization of the centres of overlap in patient subgroups was defined based on MNI coordinates. Finally, MPRAGE and T2-weighted images were visually examined to reveal possible extracerebellar pathology.
Results
Brain imaging analysis
The affected cerebellar lobules and nuclei as well as the volumes of the surgical lesions are given in Table 3 for the individual cerebellar patients. Surgical lesions were located primarily within the vermis in 16 of the 22 cases and within one of the cerebellar hemispheres in six cases (P.B., M.S., W.S., N.K., S.D. and A.B.). The volume of the lesions varied between 2.5 and 48.6 cm3 (mean: 11.8 cm3).
ID . | Vermal . | Paravermal . | . | Lateral hemispheres . | . | White matter . | Nuclei . | Volume (cm3) . | ||
---|---|---|---|---|---|---|---|---|---|---|
. | . | Right . | Left . | Right . | Left . | . | . | . | ||
A.B. | VI, CRI, CRII, VIIIA | 11.6 | ||||||||
C.D. | VI, VIIAt, VIIB, VIIIA | VI, VIIAt, VIIB, VIIIA | VI, CRI, CRII | v 1,2; pv 2,3 | 9.6 | |||||
C.S. | III, IV, V, VI, VIIA, VIIB, VIIIA, VIIIB, IX, X | CRI, CRII, VIIB, VIIIA | v 1,2,3; pv 2 | NF b, NI b | 26.2 | |||||
D.H. | V, VI, VIIAt, VIIB | VI | v 1,2; pv 2 | NF b, NI b, ND r | 8.4 | |||||
D.K. | III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | VI | CRI | pv 2,3 | NF b, NI b ND b | 25.0 | ||||
E.S. | VIIIA, VIIIB | VIIB, VIIIA, VIIIB | 4.7 | |||||||
H.S. | VIIB, VIIIA, VIIIB, IX, X | VIIB, VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | v 2,3; pv 2,3 | NF b, NI b, ND l | 12.5 | ||||
H.W. | I, II, III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 18.1 | ||||||
NI b, ND r | ||||||||||
J.B. | VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | 8.2 | |||||||
J.O. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | V, VI, CRI, VIIB, VIIIA, VIIIB, IX | VI, CRI | v 1,2,3 | NF b | 23.0 | ||||
pv 2,3; lh | NI b, ND r | |||||||||
J.R. | III, VIIAt, VIIB, VIIIA, VIIIB, IX | v 1,2,3; pv 1 | NF b, NI r, ND r | 10.8 | ||||||
M.M. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 6.0 | ||||||
M.S. | VI, CRI, CRII, VIIB, VIIIA, VIIIB | VI, CRI, CRII, VIIB, VIIIA, VIIIB | pv 2,3, lh | 48.6 | ||||||
N.K. | VIIIA, VIIIB | lh 3 | 2.7 | |||||||
P.B. | CRI, VIIIB | pv 2,3 | ND r | 2.5 | ||||||
P.U. | III, IV, V, VI, VIIAt | v 1,2 | NF b, NI l, ND l | 3.6 | ||||||
S.A. | VIIIA, IX | pv 3 | 3.6 | |||||||
S.D. | IX, X | VIIIA, VIIIB, IX, X | VIIIA, VIIIB | v 3, pv 3 | 8.7 | |||||
S.R. | VIIIB, IX, X | v 1,2,3; pv 2,3 | NF b, NI b | 4.6 | ||||||
S.S. | VIIAt, VIIB, VIIIA,VIIIB, IX, X | v 1,2,3 | NF b, NI b | 8.6 | ||||||
W.S. | VI, CRI, CRII, VIIB | 8.4 | ||||||||
Y.M. | VIIAt, VIIB, VIIIA, VIIIB, IX | VIIAt, VIIB, VIIIA, VIIIB | V 1,2,3; PV 3 | NF b, NI b, ND l | 5.2 |
ID . | Vermal . | Paravermal . | . | Lateral hemispheres . | . | White matter . | Nuclei . | Volume (cm3) . | ||
---|---|---|---|---|---|---|---|---|---|---|
. | . | Right . | Left . | Right . | Left . | . | . | . | ||
A.B. | VI, CRI, CRII, VIIIA | 11.6 | ||||||||
C.D. | VI, VIIAt, VIIB, VIIIA | VI, VIIAt, VIIB, VIIIA | VI, CRI, CRII | v 1,2; pv 2,3 | 9.6 | |||||
C.S. | III, IV, V, VI, VIIA, VIIB, VIIIA, VIIIB, IX, X | CRI, CRII, VIIB, VIIIA | v 1,2,3; pv 2 | NF b, NI b | 26.2 | |||||
D.H. | V, VI, VIIAt, VIIB | VI | v 1,2; pv 2 | NF b, NI b, ND r | 8.4 | |||||
D.K. | III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | VI | CRI | pv 2,3 | NF b, NI b ND b | 25.0 | ||||
E.S. | VIIIA, VIIIB | VIIB, VIIIA, VIIIB | 4.7 | |||||||
H.S. | VIIB, VIIIA, VIIIB, IX, X | VIIB, VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | v 2,3; pv 2,3 | NF b, NI b, ND l | 12.5 | ||||
H.W. | I, II, III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 18.1 | ||||||
NI b, ND r | ||||||||||
J.B. | VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | 8.2 | |||||||
J.O. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | V, VI, CRI, VIIB, VIIIA, VIIIB, IX | VI, CRI | v 1,2,3 | NF b | 23.0 | ||||
pv 2,3; lh | NI b, ND r | |||||||||
J.R. | III, VIIAt, VIIB, VIIIA, VIIIB, IX | v 1,2,3; pv 1 | NF b, NI r, ND r | 10.8 | ||||||
M.M. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 6.0 | ||||||
M.S. | VI, CRI, CRII, VIIB, VIIIA, VIIIB | VI, CRI, CRII, VIIB, VIIIA, VIIIB | pv 2,3, lh | 48.6 | ||||||
N.K. | VIIIA, VIIIB | lh 3 | 2.7 | |||||||
P.B. | CRI, VIIIB | pv 2,3 | ND r | 2.5 | ||||||
P.U. | III, IV, V, VI, VIIAt | v 1,2 | NF b, NI l, ND l | 3.6 | ||||||
S.A. | VIIIA, IX | pv 3 | 3.6 | |||||||
S.D. | IX, X | VIIIA, VIIIB, IX, X | VIIIA, VIIIB | v 3, pv 3 | 8.7 | |||||
S.R. | VIIIB, IX, X | v 1,2,3; pv 2,3 | NF b, NI b | 4.6 | ||||||
S.S. | VIIAt, VIIB, VIIIA,VIIIB, IX, X | v 1,2,3 | NF b, NI b | 8.6 | ||||||
W.S. | VI, CRI, CRII, VIIB | 8.4 | ||||||||
Y.M. | VIIAt, VIIB, VIIIA, VIIIB, IX | VIIAt, VIIB, VIIIA, VIIIB | V 1,2,3; PV 3 | NF b, NI b, ND l | 5.2 |
NF = nucleus fastigius; NI = nucleus interpositus; ND = nucleus dentatus; b both nuclei affected; l = left nucleus, r = right nucleus; v1–v3 = vermal subregions (v1 = white matter lobules I–V, v2 = white matter of lobules VI and VII, v3 = white matter of lobules VIII–X); pv1–pv3 = paravermal subregions (pv1 = white matter of lobules I–V, pv2 = white matter of lobules VI and VII, pv3 = white matter of lobules VIII–X). Sagittal subregions according to Luft et al. (1998): x-range of −10 to +10 mm = vermis, x-range of −10 to −24 mm (left), and +10 to +24 mm (right) = paravermis, x-range of −24 (left) and +24 mm (right) to the outmost left and right = lateral hemispheres.
ID . | Vermal . | Paravermal . | . | Lateral hemispheres . | . | White matter . | Nuclei . | Volume (cm3) . | ||
---|---|---|---|---|---|---|---|---|---|---|
. | . | Right . | Left . | Right . | Left . | . | . | . | ||
A.B. | VI, CRI, CRII, VIIIA | 11.6 | ||||||||
C.D. | VI, VIIAt, VIIB, VIIIA | VI, VIIAt, VIIB, VIIIA | VI, CRI, CRII | v 1,2; pv 2,3 | 9.6 | |||||
C.S. | III, IV, V, VI, VIIA, VIIB, VIIIA, VIIIB, IX, X | CRI, CRII, VIIB, VIIIA | v 1,2,3; pv 2 | NF b, NI b | 26.2 | |||||
D.H. | V, VI, VIIAt, VIIB | VI | v 1,2; pv 2 | NF b, NI b, ND r | 8.4 | |||||
D.K. | III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | VI | CRI | pv 2,3 | NF b, NI b ND b | 25.0 | ||||
E.S. | VIIIA, VIIIB | VIIB, VIIIA, VIIIB | 4.7 | |||||||
H.S. | VIIB, VIIIA, VIIIB, IX, X | VIIB, VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | v 2,3; pv 2,3 | NF b, NI b, ND l | 12.5 | ||||
H.W. | I, II, III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 18.1 | ||||||
NI b, ND r | ||||||||||
J.B. | VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | 8.2 | |||||||
J.O. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | V, VI, CRI, VIIB, VIIIA, VIIIB, IX | VI, CRI | v 1,2,3 | NF b | 23.0 | ||||
pv 2,3; lh | NI b, ND r | |||||||||
J.R. | III, VIIAt, VIIB, VIIIA, VIIIB, IX | v 1,2,3; pv 1 | NF b, NI r, ND r | 10.8 | ||||||
M.M. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 6.0 | ||||||
M.S. | VI, CRI, CRII, VIIB, VIIIA, VIIIB | VI, CRI, CRII, VIIB, VIIIA, VIIIB | pv 2,3, lh | 48.6 | ||||||
N.K. | VIIIA, VIIIB | lh 3 | 2.7 | |||||||
P.B. | CRI, VIIIB | pv 2,3 | ND r | 2.5 | ||||||
P.U. | III, IV, V, VI, VIIAt | v 1,2 | NF b, NI l, ND l | 3.6 | ||||||
S.A. | VIIIA, IX | pv 3 | 3.6 | |||||||
S.D. | IX, X | VIIIA, VIIIB, IX, X | VIIIA, VIIIB | v 3, pv 3 | 8.7 | |||||
S.R. | VIIIB, IX, X | v 1,2,3; pv 2,3 | NF b, NI b | 4.6 | ||||||
S.S. | VIIAt, VIIB, VIIIA,VIIIB, IX, X | v 1,2,3 | NF b, NI b | 8.6 | ||||||
W.S. | VI, CRI, CRII, VIIB | 8.4 | ||||||||
Y.M. | VIIAt, VIIB, VIIIA, VIIIB, IX | VIIAt, VIIB, VIIIA, VIIIB | V 1,2,3; PV 3 | NF b, NI b, ND l | 5.2 |
ID . | Vermal . | Paravermal . | . | Lateral hemispheres . | . | White matter . | Nuclei . | Volume (cm3) . | ||
---|---|---|---|---|---|---|---|---|---|---|
. | . | Right . | Left . | Right . | Left . | . | . | . | ||
A.B. | VI, CRI, CRII, VIIIA | 11.6 | ||||||||
C.D. | VI, VIIAt, VIIB, VIIIA | VI, VIIAt, VIIB, VIIIA | VI, CRI, CRII | v 1,2; pv 2,3 | 9.6 | |||||
C.S. | III, IV, V, VI, VIIA, VIIB, VIIIA, VIIIB, IX, X | CRI, CRII, VIIB, VIIIA | v 1,2,3; pv 2 | NF b, NI b | 26.2 | |||||
D.H. | V, VI, VIIAt, VIIB | VI | v 1,2; pv 2 | NF b, NI b, ND r | 8.4 | |||||
D.K. | III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | VI | CRI | pv 2,3 | NF b, NI b ND b | 25.0 | ||||
E.S. | VIIIA, VIIIB | VIIB, VIIIA, VIIIB | 4.7 | |||||||
H.S. | VIIB, VIIIA, VIIIB, IX, X | VIIB, VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | v 2,3; pv 2,3 | NF b, NI b, ND l | 12.5 | ||||
H.W. | I, II, III, IV, V, VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 18.1 | ||||||
NI b, ND r | ||||||||||
J.B. | VIIIA, VIIIB, IX | VIIIA, VIIIB, IX | 8.2 | |||||||
J.O. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | V, VI, CRI, VIIB, VIIIA, VIIIB, IX | VI, CRI | v 1,2,3 | NF b | 23.0 | ||||
pv 2,3; lh | NI b, ND r | |||||||||
J.R. | III, VIIAt, VIIB, VIIIA, VIIIB, IX | v 1,2,3; pv 1 | NF b, NI r, ND r | 10.8 | ||||||
M.M. | VI, VIIAt, VIIB, VIIIA, VIIIB, IX, X | v 1,2,3 | NF b | 6.0 | ||||||
M.S. | VI, CRI, CRII, VIIB, VIIIA, VIIIB | VI, CRI, CRII, VIIB, VIIIA, VIIIB | pv 2,3, lh | 48.6 | ||||||
N.K. | VIIIA, VIIIB | lh 3 | 2.7 | |||||||
P.B. | CRI, VIIIB | pv 2,3 | ND r | 2.5 | ||||||
P.U. | III, IV, V, VI, VIIAt | v 1,2 | NF b, NI l, ND l | 3.6 | ||||||
S.A. | VIIIA, IX | pv 3 | 3.6 | |||||||
S.D. | IX, X | VIIIA, VIIIB, IX, X | VIIIA, VIIIB | v 3, pv 3 | 8.7 | |||||
S.R. | VIIIB, IX, X | v 1,2,3; pv 2,3 | NF b, NI b | 4.6 | ||||||
S.S. | VIIAt, VIIB, VIIIA,VIIIB, IX, X | v 1,2,3 | NF b, NI b | 8.6 | ||||||
W.S. | VI, CRI, CRII, VIIB | 8.4 | ||||||||
Y.M. | VIIAt, VIIB, VIIIA, VIIIB, IX | VIIAt, VIIB, VIIIA, VIIIB | V 1,2,3; PV 3 | NF b, NI b, ND l | 5.2 |
NF = nucleus fastigius; NI = nucleus interpositus; ND = nucleus dentatus; b both nuclei affected; l = left nucleus, r = right nucleus; v1–v3 = vermal subregions (v1 = white matter lobules I–V, v2 = white matter of lobules VI and VII, v3 = white matter of lobules VIII–X); pv1–pv3 = paravermal subregions (pv1 = white matter of lobules I–V, pv2 = white matter of lobules VI and VII, pv3 = white matter of lobules VIII–X). Sagittal subregions according to Luft et al. (1998): x-range of −10 to +10 mm = vermis, x-range of −10 to −24 mm (left), and +10 to +24 mm (right) = paravermis, x-range of −24 (left) and +24 mm (right) to the outmost left and right = lateral hemispheres.
Of the 16 patients with vermal lesions, the NF were affected bilaterally in 12 patients. These 12 cases also showed affected NI. In eight of the 12 cases, the lesion extended into the dentate nucleus mainly on one side (see Table 3). In one patient (C.D.) with a vermal lesion, only the dentate nucleus was affected, as was the case in two patients with hemispheral lesions (P.B. and N.K.).
In two children (H.S. and D.K.), surgical lesions were accompanied by possible cerebellar infarction. These areas were included in the individual cerebellar lesion. In one case (S.D.), a benign subarachnoid cerebellar cyst was present. Mild signs of focal cerebellar atrophy were present in four cases (H.S., P.B., H.W. and S.R.). Signs of acute or chronic hydrocephalus were absent in all cerebellar patients. At the time of the testing, four patients were provided with a permanent ventriculo-peritoneal shunt and one with a ventriculo-atrial shunt. None of the patients had extracerebellar lesions except two with additional lesions of the brainstem (Y.M. and J.B.). In J.B., the surgical lesion affected the medulla oblongata. In Y.M., an additional lesion was present in the mesencephalon, corresponding to an old haemorrhage or cavernoma.
Postural control
All patients revealed normal sway kinematics during stationary platform conditions (conditions 1–3; see Table 2). However, in the last two test conditions when platform tilt was sway-referenced and the eyes were closed or vision was also sway-referenced, excessive centre of gravity (COG) motion that even led to falls or to subjects stepping off the force plate became manifest in a subgroup of patients. Out of 22 patients, 14 patients (64%) exhibited enlarged sway areas and sway path lengths beyond the range of the control group in these last two conditions that primarily tested the integrity of vestibular–cerebellar loops. Seven of those patients also lost balance in at least three trials during the last six trials (we here define ‘abnormal posture’ as sway outside the range of the control group or the loss of balance as indicated by stepping off the platform). Figure 1 shows the median sway area of each subject under each of the six sensory conditions and illustrates how the sway area increased in a subset of patients when they had to rely on vestibular inputs to maintain balance.
When overlaying the MRIs of those patients that exhibited excessive sway outside the range of the control group, the region with the highest overlap (12 out of 14) included the NF and in 11 out of 14 patients also the NI (Fig. 2A). In patients with normal postural responses, the highest region of overlap included four out of eight patients, where the overlap was located in paravermal regions of lobuli VIIIA and VIIIB and did not include NI and NF. Some of the patients with abnormal postural sway had received chemo- and/or radiation therapy, which might have affected extracerebellar neural structures involved in postural control, i.e. extracerebellar as well as cerebellar lesions could have caused postural dyscontrol in this patient subgroup. We therefore performed a separate lesion analysis on all patients who had not received cranial irradiation or chemotherapy (n = 14). Eight of these 14 patients had abnormal postural sway. The MRI overlay graph in Fig. 3A reveals that the lesioned areas involved the NF and NI in all eight patients and dorsomedial portions of the dentate nucleus in six out of eight patients. Thus, in this patient subgroup, the excessive sway is linked to their surgical cerebellar lesions. In the remaining six patients, whose postural sway was within the limits of the control group, the region of maximum overlap was located in paravermal regions (VIIIA and VIIIB) and only included three of the six patients.
To document that a permanent lesion of NF affects equilibrium control, Fig. 4 shows representative MRIs of two patients with lesioned NF who exhibited abnormal postural sway and compares their performance with that of two patients with intact NF and with the corresponding sway pattern of two control subjects. The data in Fig. 5 substantiate this result by showing that out of the 13 patients who showed an abnormal sway area, 12 patients had a lesion affecting one or both NF. The remaining patient (J.B.) had received chemotherapy and cranial irradiation after surgery, which might have affected the PNS or processing of the somatosensory cortex. In addition, she also presented an additional lesion within the mesencephalon.
Upper limb function
Twelve patients (54%) showed moderate clinical signs of upper limb ataxia as assessed by clinical examination. Their upper limb WFN ataxia score ranged between 2 and 10. During both pointing tasks, only two patients (J.R. and Y.M.) exhibited marked intention tremor at the termination of movement. Kinematic measures complemented the clinical finding and revealed prolonged mean acceleration and deceleration times during the two pointing tasks. Deceleration time reflects the time that the index finger slows down after reaching peak velocity (about midway through the pointing motion). During arm pointing, 11 patients exhibited prolonged deceleration times that exceeded at least 110% of the control group range, while the deceleration times of the remaining patients fell within the range of the control group (see Fig. 6). It is noteworthy that the results for the finger pointing task were less consistent. Only two patients (M.M. and D.H.) exhibited clearly prolonged deceleration times. In addition, one patient (J.O.), who clinically showed signs of upper limb ataxia with a documented impaired upper limb function (Timmann et al., 1999), revealed acceleration and deceleration times within the normal range during both pointing tasks. When overlaying the transversal MRIs of those patients with prolonged deceleration times and adding the image of patient J.O., the region with the highest overlap (11 out of 12) included the NI and NF. In 10 out of 12 patients, the dentate nuclei were also affected (Fig. 7A). In the remaining patients, the highest region of overlap included four out of 10 patients. In these kinematically normal patients, the overlap did not include NI and NF, but was located paravermally in lobulus VIIIA (Fig. 7B). Note that part of the ventral dentate nucleus was affected in two out of the 10 patients (P.B. and N.K.). Because some patients with abnormal arm kinematics had received chemo- and/or radiation therapy, which might have affected extracerebellar motor systems, we also obtained an overlap for a subset of patients without radiation or chemotherapy. Consequently, in this patient subgroup (n = 8), the impaired arm kinematics were linked to their surgical cerebellar lesions. The subgroup consisted of the same patients as shown in Fig. 3A.
To document that a permanent lesion involving the NI or dentate nuclei is associated with impaired upper limb temporal kinematics, Fig. 8 shows the individual mean deceleration times of all patients with lesions affecting the NI and dentate nuclei. The data revealed that the majority of these patients exhibited prolonged deceleration phases in the arm pointing task.
Relationship between motor behaviour, age at surgery and time past surgery
The correlation between mean deceleration time and WFN upper limb score was r = 0.49 (P > 0.0001). Yet, within the patient sample, none of the arm kinematic measures correlated significantly with the age at surgery, recovery time (years passed since surgery) or lesion volume. Age at surgery, recovery time or lesion volume never explained > 4.5% of the total variance of any kinematic measure (acceleration time, deceleration time, peak resultant velocity and peak resultant acceleration).
For the postural control measures and the above clinical predictor variables, a similar relationship emerged. The correlation between sway path and the WFN posture score was 0.6 (P > 0.001). Yet, neither age at surgery nor recovery time yielded significant correlations with these variables of postural stability (r values range: 0.07 to −0.3). Lesion volume was also not a significant predictor of sway path (r = 0.065). Post-surgical chemo- or radiation therapy only explained up to 9% of the variance in sway path or sway area.
Cognitive function
Eighteen out of 22 patients had a digit span memory score within the range of the control group. Three patients scored below and one patient above the range of the control group. Separate analyses of the forward digit span, which is considered a measure of attention, and the backward digit span, which is thought to reflect working memory, did not yield significant group differences (P > 0.05). Table 4 lists the respective mean values.
. | Cerebellar patients with CRT (n = 6) . | Cerebellar patients without CRT (n = 14) . | Controls (n = 14) . |
---|---|---|---|
Digit span, forward (max. score: 12) | 6.7 (1.5) | 6.5 (1.9) | 7.7 (1.9) |
Digit span, backward (max. score: 12) | 5.2 (1.7) | 5.7 (1.3) | 6.1 (1.4) |
Digit span, pooled | 11.5 (2.9) | 12.2 (2.6) | 13.9 (2.5) |
Block board, forward (max. score: 14) | 7.0 (1.8) | 8.9 (1.4) | 9.8 (1.7) |
Block board, backward (max. score: 12) | 7.3 (1.9) | 8.0 (1.6) | 9.9 (1.4) |
Block board, pooled | 14.3 (3.1) | 16.9 (2.6) | 19.6 (2.5) |
. | Cerebellar patients with CRT (n = 6) . | Cerebellar patients without CRT (n = 14) . | Controls (n = 14) . |
---|---|---|---|
Digit span, forward (max. score: 12) | 6.7 (1.5) | 6.5 (1.9) | 7.7 (1.9) |
Digit span, backward (max. score: 12) | 5.2 (1.7) | 5.7 (1.3) | 6.1 (1.4) |
Digit span, pooled | 11.5 (2.9) | 12.2 (2.6) | 13.9 (2.5) |
Block board, forward (max. score: 14) | 7.0 (1.8) | 8.9 (1.4) | 9.8 (1.7) |
Block board, backward (max. score: 12) | 7.3 (1.9) | 8.0 (1.6) | 9.9 (1.4) |
Block board, pooled | 14.3 (3.1) | 16.9 (2.6) | 19.6 (2.5) |
SDs are in parentheses. CRT = chemo- and radiation therapy. Two out of eight patients who had received CRT scored within the normal range in both tests.
. | Cerebellar patients with CRT (n = 6) . | Cerebellar patients without CRT (n = 14) . | Controls (n = 14) . |
---|---|---|---|
Digit span, forward (max. score: 12) | 6.7 (1.5) | 6.5 (1.9) | 7.7 (1.9) |
Digit span, backward (max. score: 12) | 5.2 (1.7) | 5.7 (1.3) | 6.1 (1.4) |
Digit span, pooled | 11.5 (2.9) | 12.2 (2.6) | 13.9 (2.5) |
Block board, forward (max. score: 14) | 7.0 (1.8) | 8.9 (1.4) | 9.8 (1.7) |
Block board, backward (max. score: 12) | 7.3 (1.9) | 8.0 (1.6) | 9.9 (1.4) |
Block board, pooled | 14.3 (3.1) | 16.9 (2.6) | 19.6 (2.5) |
. | Cerebellar patients with CRT (n = 6) . | Cerebellar patients without CRT (n = 14) . | Controls (n = 14) . |
---|---|---|---|
Digit span, forward (max. score: 12) | 6.7 (1.5) | 6.5 (1.9) | 7.7 (1.9) |
Digit span, backward (max. score: 12) | 5.2 (1.7) | 5.7 (1.3) | 6.1 (1.4) |
Digit span, pooled | 11.5 (2.9) | 12.2 (2.6) | 13.9 (2.5) |
Block board, forward (max. score: 14) | 7.0 (1.8) | 8.9 (1.4) | 9.8 (1.7) |
Block board, backward (max. score: 12) | 7.3 (1.9) | 8.0 (1.6) | 9.9 (1.4) |
Block board, pooled | 14.3 (3.1) | 16.9 (2.6) | 19.6 (2.5) |
SDs are in parentheses. CRT = chemo- and radiation therapy. Two out of eight patients who had received CRT scored within the normal range in both tests.
Visual span memory was only impaired in a subgroup of six patients who all had received radiation and/or chemotherapy after surgery. This patient subgroup was significantly different from the control group (P < 0.007). The respective mean scores are listed in Table 4. For the adolescent controls, the combined score (forward and backward) corresponded approximately to the 73rd–80th percentile of the healthy German population, and for young adults approximately to the 75th percentile of the population (Härting et al., 1998).
Discussion
Age at surgery and time since surgery are not determinants of long-term recovery
It has been a long-held notion that brain injury is better compensated at a young age and that children have a better prognosis to regain function than adults. Studies on rodents after hemicerebellectomy also stress that lesions at an early developmental age are associated with a better recovery of motor function (Molinari et al., 1990). Our study cannot confirm that age at surgery is an important predictor of motor or cognitive recovery after cerebellar damage in humans. The functional recovery of patients who experienced surgery in the first 4 years of their lives was not consistently superior to that of patients with surgery during late childhood or adolescence. None of the recorded postural, upper limb or memory measures correlated significantly with the age at surgery. This implies that age at surgery is not a helpful prognostic marker of how motor and memory function will recover after cerebellar injury. Our results are in line with a previous study that did not find differences in tandem walk performance in adolescent and adult survivors of childhood cerebellar medulloblastoma (Dennis et al., 1999). The findings of both studies suggest that cerebellar lesions during childhood are not necessarily better compensated for than similar lesions experienced during adulthood.
In addition, the time since surgery did not determine the extent of recovery. In our sample of patients, the time since surgery ranged between 3 and 17 years. We found no clear sign that more time past surgery translated into a more complete motor recovery. In fact, none of the motor or cognitive measures correlated significantly with time past surgery. This does not imply that time per se is not a factor during short-term recovery after tumour resection. It is well known that patients with cortical or subcortical strokes experience behavioural improvements in the immediate weeks and months after the ictus (Green, 2003). However, all of our patients were well past the first 6 months after surgery, when processes of brain reorganization and neuronal plasticity can be expected (Fujii and Nakada, 2003). Thus, it appears that once this initial period of plastic changes has passed, any additional time spent after surgery has little impact on improved function.
Lesion site but not lesion volume predicts long-term motor recovery
The extent and the location of the cerebellar lesions naturally varied because of the tumour site. We found that the volume of the lesion was not predictive of long-term motor function. In fact, the patient with the largest lesion showed normal postural responses and intact upper limb coordination. With respect to the complete patient group, lesion volume did not correlate significantly with any of the recorded motor measures. In contrast, the lesion site was found to be an important factor for long-term motor recovery. Specifically, we found that when lesions involved the deep cerebellar nuclei, the resulting impairments had a lasting effect.
During clinical examination, postural problems were not necessarily prominent and were considered mild (0–5.5 on the WFN posture scale). Yet, when vision was absent and ankle proprioceptive signals did not indicate body orientation (sway-referenced), patients had to rely solely on vestibular input. Under these deprived sensory conditions, a subgroup of patients with lesions including NF exhibited severe postural dyscontrol that in some cases even led to falling. It is known from experiments with monkeys that neurons in the rostral part of the NF respond to vestibular stimulation (Thach, 1970; Siebold et al., 1999) and are not modulated by individual eye movements (Buttner et al., 1991). Unilateral axon-sparing lesions of the NF result in ipsilateral limb extensor atonia and contralateral limb extensor hypertonus (Imperato et al., 1984), which demonstrates that the output of rostral fastigial neurons affects the descending control of limb muscles. The behavioural manifestation of NF inactivation in monkeys is a loss of equilibrium control during sitting, standing and walking (Thach et al., 1992). Assuming that fastigial neurons play a similar role in human posture, it then becomes plausible why our patients with lesioned NF lost postural control when they had to rely exclusively on vestibular signals to maintain equilibrium.
It is obvious that the majority of those patients who had not received chemo- and/or radiation therapy but exhibited postural problems had a split vermis (five out of eight). It thus could be argued that the separation of parallel fibres crossing the vermis and not the loss of fastigial neurons is the critical lesion leading to disequilibrium (Bastian et al., 1998). Against this argument speaks that three out of eight patients with abnormal posture had no vermal split, but all eight patients had a lesioned NF. In addition, one patient with a split vermis exhibited no postural deficits. Hence, it is not necessarily the split of the vermis, but the lesioning of NF that seems critical for postural control. The fact that vermal split is often associated with postural dysfunction consequently might be an effect of the surgical procedure where the NF were not spared during splitting.
During clinical examination, 54% of the patients showed moderate signs of upper limb ataxia, with only two patients exhibiting a marked intention tremor. All patients were able to perform the two pointing tasks. It is known that cerebellar patients tend to move slower than healthy controls during goal-directed arm movements, which is usually seen not as a generic cerebellar deficit but as an adapted strategy to avoid dysmetric movements. In this respect, the increased deceleration times observed in our patients were not a sign of a genuine deficit, but should be considered as part of a compensation strategy, i.e. if an impaired motor system does not receive adequate information about the magnitude and the time course of the external or passive limb forces, it cannot control a multi-joint arm in point-to-point movements (Konczak et al., 1997; Topka et al., 1998). However, if the arm is moved slowly, thus avoiding large interaction torques, the hand can be brought precisely to the target without overshooting.
In this study, we intentionally did not force patients to move as fast as possible, in order to elicit dysmetria. Instead we allowed all participants to move with their preferred speed, so we could examine the actual consequences of the tumour resection on upper limb function. Single-joint finger movements were intact in the vast majority of the patients (91%). However, 11 patients (50%) exhibited abnormal deceleration times during the 3D multi-joint arm pointing task. This finding underlines the notion that cerebellar processing is more critical for multi-joint control, since more complex external force patterns need to be compensated to achieve limb coordination (Bastian et al., 1996; Topka et al., 1998).
The corresponding MRI analysis revealed that all patients with abnormal deceleration times who did not receive chemo- and/or radiation therapy had NI lesions. In addition, the region of highest lesion overlap of nine of the patients included dorsomedial portions of nucleus dentatus. Neuroanatomical studies on monkeys showed that the dorsal portion of the nucleus dentatus projects to primary and premotor areas of the neocortex and is thought to modulate mainly motor cortical output (Dum and Strick, 2003). It is further known that substantial output of the intermediate cerebellar zone is channelled through the NI. Both nuclear regions (NI and dentate nucleus) have large projections to the magnocellular red nucleus (Kennedy et al., 1986) and to the primary motor cortex via the ventrolateral thalamus (Middleton and Strick, 1997), i.e. the efferent projections from the intermediate cerebellar zone can indirectly influence the control of reaching and grasping. In light of these neuroanatomical projections, the abnormal arm kinematics of our patients becomes plausible. Interestingly, the two patients with lesions of the ventral dentate (P.B. and N.K.) showed normal arm kinematics, which is consistent with the notion that ventral portions of the dentate are involved in non-motor functions (Dum and Strick, 2003).
Development of memory function after cerebellar tumour resection
Cognitive impairments after cerebellar tumour resection in childhood have been described previously (Levisohn et al., 2000; Riva and Giorgi et al., 2000; Scott et al., 2001; Steinlin et al., 2003; Aarsen et al., 2004). The current study focused on verbal and visuospatial short-term memory function as select aspects of cognitive function. We found that cognitive recovery was not a function of age at surgery, but was only impaired in those patients who had received chemotherapy or cranial irradiation therapy after tumour resection. This patient subgroup had a normal digit span memory, but their average visual memory span was reduced by 30% when compared with the control group. These results corroborate previous findings that chemo- and radiation therapy can lead to a decline in overall intellectual function (Silber et al., 1992; Abayomi, 1996; Reimers et al., 2003). As a caveat, it should be noted that we cannot exclude the possibility that other cognitive deficits would have emerged in our patients if a more comprehensive neuropsychological test battery had been administered.
Abnormal verbal working memory performance after cerebellar injury has been reported previously in children (Levisohn et al., 2000; Riva and Giorgi et al., 2000; Scott et al., 2001; Steinlin et al., 2003). Yet, in two of the studies, children with abnormal findings had received radiotherapy (six of seven children included in the study of Scott et al., 2001) or chemotherapy (four of five children who performed below average in the study of Levisohn et al., 2000). The children tested by Steinlin et al. (2004) and Riva and Giorgi (2000) did not receive chemo- and radiotherapy. Riva and Giorgi, however, examined children with acute lesions and suggested that findings may be transient. Thus, their findings and our results on post-acute children are not in disagreement. In other words, cerebellar injury might lead to short-term cognitive deficits in acute patients, yet, working memory of long-term survivors of childhood cerebellar tumours is not compromised, if they had not received chemo- and radiotherapy.
With respect to visual sequential memory, a recent report seemed to indicate that this aspect of working memory is impaired in patients after a childhood posterior fossa tumour resection (Steinlin et al., 2004). In this study, patients older than 18 years had performed normally in the block board test. In contrast, six out of 13 patients younger than 16 years of age were considered to be abnormal, although the validity of reference values for the youngest patients could not be established. We could not replicate these findings of impaired short-term memory in our adolescent and adult patient population. Patients who had not received radiation or chemotherapy had essentially a normal memory function.
Conclusion
Our data indicate that cerebellar damage inflicted at a young age is not necessarily better compensated than damage experienced in later childhood or adolescence. Thus, the notion that CNS lesions experienced at a young age have lesser consequences for later functioning than similar lesions occurring at later stages of life is not true for injuries affecting the cerebellum. We found that the lesion site and not age at surgery is critical for the motor recovery. Specifically, lesions of the deep cerebellar nuclei experienced at any age during childhood and adolescence are not compensated well through development. In essence, this result confirms for humans previous findings known from apes (Eckmiller and Westheimer, 1983) that early lesions affecting the cerebellar outflow nuclei are not well compensated.
We wish to thank the many patients who invested considerable time to be part of this study, all other participants for their support, and Beate Brol and Hans-Georg Elles for helping with the experimental set-up and the data collection. This research was supported by a grant from the Deutsche Forschungsgemeinschaft TI 239/5-1 to D.T. and by a sabbatical awarded to J.K. from the University of Minnesota.
References
Aarsen FK, Van Dongen HR, Paquier PF, Van Mourik M, Catsman-Berrevoets CE. Long-term sequelae in children after cerebellar astrocytoma surgery.
Bastian AJ, Martin TA, Keating JG, Thach WT. Cerebellar ataxia: abnormal control of interaction torques across multiple joints.
Bastian AJ, Mink JW, Kaufman BA, Thach WT. Posterior vermal split syndrome.
Botterell EH, Fulton JF. Functional localization in the cerebellum of primates. II. Lesions of the midline structures and deep nuclei.
Botterell EH, Fulton JF. Functional localization in the cerebellum of primates. III. Lesions of the hemispheres (neocerebellum).
Buttner U, Fuchs AF, Markert-Schwab G, Buckmaster P. Fastigial nucleus activity in the alert monkey during slow eye and head movements.
Crivello F, Schormann T, Tzourio-Mazoyer N, Roland PE, Zilles K, Mazoyer BM. Comparison of spatial normalization procedures and their impact on functional maps.
Dennis M, Spiegler BJ, Hetherington R, Greenberg ML. Neuropsychological sequelae of treatment of children with medulloblastoma.
Dennis M, Hetherington CR, Spiegler BJ, Barnes MA. Functional consequences of congenital and cerebellar dysmorphologies and acquired cerebellar lesions of childhood. In: Broman SH, Fletcher JM, editors. The changing nervous system: neurobehavioral consequences of early brain disorders. Oxford: Oxford University Press;
Dichgans J, Mauritz KH. Patterns and mechanisms of postural instability in patients with cerebellar lesions. In: Desmedt JE, editor. Motor control mechanisms in health and disease. New York: Raven Press;
Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb FP, et al. MRI atlas of the human cerebellar nuclei.
Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex.
Dum RP, Li C, Strick PL. Motor and nonmotor domains in the monkey dentate.
Eckmiller R, Westheimer G. Compensation of oculomotor deficits in monkeys with neonatal cerebellar ablations.
Fujii Y, Nakada T. Cortical reorganization in patients with subcortical hemiparesis: neural mechanisms of functional recovery and prognostic implication.
Gramsbergen A. Consequences of cerebellar lesions at early and later ages: clinical relevance of animal experiments.
Growdon JH, Chambers WW, Liu CN. An experimental study of cerebellar dyskinesia in the rhesus monkey.
Härting C, Markowitsch HJ, Neufeld H, Calabrese P, Deisinger K, Kessler J, editors. WMS-R Wechsler Gedächtnistest–Revidierte Fassung: Hans Huber Verlag;
Hetherington R, Dennis M, Spiegler B. Perception and estimation of time in long-term survivors of childhood posterior fossa tumors.
Imperato A, Nicoletti F, Diana M, Scapagnini U, Di Chiara G. Fastigial influences on postural tonus as studied by kainate lesions and by local infusion of GABAergic drugs in the rat.
Jansen J, Brodal A. Experimental studies on the intrinsic fibers of the cerebellum. II. The cortico-nuclear projection.
Kennedy PR, Gibson AR, Houk JC. Functional and anatomic differentiation between parvicellular and magnocellular regions of red nucleus in the monkey.
Konczak J, Borutta M, Dichgans J. Development of goal-directed reaching in infants: II. Learning to produce task-adequate patterns of joint torque.
Leiner HC, Leiner AL, Dow RS. Cognitive and language functions of the cerebellum.
Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population.
Little WJ. On the influence of abnormal parturition, difficult labours, premature birth and asphxia neonatorum on the mental and physical condition of the child, especially in relation to deformities.
Luft AR, Skalej M, Welte D, Kolb R, Bürk K, Schulz JB, et al. A new semiautomated, three-dimensional technique allowing precise quantification of total and regional cerebellar volume using MRI.
Mackel R. The role of the monkey sensory cortex in the recovery from cerebellar injury.
Mason R, Miller LE, Baker JF, Houk JC. Organization of reaching and grasping movements in the primate cerebellar nuclei as revealed by focal muscimol inactivations.
Matano S. A volumetric comparison of the vestibular nuclei in primates.
Matano S. Brief communication: proportions of the ventral half of the cerebellar dentate nucleus in humans and great apes.
Middleton FA, Strick PL. Dentate output channels: motor and cognitive components.
Middleton FA, Strick PL. Cerebellar output: motor and cognitive channels.
Molinari M, Petrosini L, Gremoli T. Hemicerebellectomy and motor behaviour in rats. II. Effects of cerebellar lesion performed at different developmental stages.
O'Donoghue DL, Kartje-Tillotson G, Neafsey EJ, Castro AJ. A study of forelimb movements evoked by intracortical microstimulation after hemicerebelectomy in newborn young and adult rats.
Orsini A. Corsi's block-tapping test: standardization and concurrent validity with WISC-R for children aged 11 to 16.
Orsini A, Chiacchio L, Cinque M, Cocchiaro C, Schiappa O, Grossi D. Effects of age, education and sex on two tests of immediate memory: a study of normal subjects from 20 to 99 years of age.
Reimers TS, Ehrenfels S, Mortensen EL, Schmiegelow M, Sonderkaer S, Carstensen H, et al. Cognitive deficits in long-term survivors of childhood brain tumors: identification of predictive factors.
Riva D, Giorgi C. The cerebellum contributes to higher functions during development—evidence from a series of children surgically treated for posterior fossa tumours.
Salmond CH, Ashburner J, Vargha-Khadem F, Connelly A, Gadian DG, Friston KJ. The precision of anatomical normalization in the medial temporal lobe using spatial basis functions.
Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome.
Schmahmann JD, Dojon J, Toga AW, Petrides M, Evans AC. MRI atlas of the human cerebellum. San Diego: Academic Press;
Schoch B, Gorissen B, Richter S, Ozimek A, Kaiser O, Dimitrova A, et al. Do children with focal cerebellar lesions show deficits in shifting attention?
Scott RB, Stoodley CJ, Anslow P, Paul C, Stein JF, Sugden EM, et al. Lateralized cognitive deficits in children following cerebellar lesions.
Siebold C, Kleine JF, Glonti L, Tchelidze T, Buttner U. Fastigial nucleus activity during different frequencies and orientations of vertical vestibular stimulation in the monkey.
Silber JH, Radcliffe J, Peckham V, Perilongo G, Kishani P, Fridman M, et al. Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.
Steinlin M, Imfeld S, Zulauf P, Boltshauser E, Lövblad K-O, Ridolfi Lüthy A, et al. Neuropsychological long-term sequelae after posterior fossa tumour resection during childhood.
Thach WT. Discharge of cerebellar neurons related to two maintained postures and two prompt movements. I. Nuclear cell output.
Thach WT, Kane SA, Mink JW, Goodkin HP. Cerebellar output: multiple maps and modes of control in movement coordination. In: Llinas R, Stelo, C, editors. The cerebellum revisited. New York: Springer-Verlag;
Timmann D, Watts S, Hore J. Failure of cerebellar patients to time finger opening precisely causes ball high–low inaccuracy in overarm throws.
Topka H, Konczak J, Schneider K, Boose A, Dichgans J. Multi-joint arm movements in cerebellar ataxia: abnormal control of movement dynamics.
Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, et al. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology.
Author notes
1Human Sensorimotor Control Laboratory and 2Department of Neurology, University of Minnesota, USA, 3Department of Neurosurgery, 4Department of Neurology and 5Department of Neuroradiology, Universität Duisburg-Essen, Germany
- radiation therapy
- chemotherapy regimen
- adolescent
- cell nucleus
- cerebellar neoplasms
- cerebellar nuclei
- child
- deceleration
- short-term memory
- recovery of function
- surgical procedures, operative
- arm
- cerebellum
- memory
- posture
- upper extremity function
- middle childhood
- brain imaging
- cerebellar lesion
- cognitive ability
- posture, abnormal
- body posture normal
- deceleration time slope
- developmental age
- posturography
- postural sway when standing