Case Report

Thalamic lesions in a long-surviving child with spinal

muscular atrophy type I: MRI and EEG findings

Yasushi Itoa,b,*, Satoko Kumadaa, Akira Uchiyamaa, Kayoko Saitob, Makiko Osawab,Akira Yagishitac, Kiyoko Kurataa, Masaharu Hayashid

aDepartment of Pediatrics, Metropolitan Fuchu Medical Center for Severe Motor and Intellectual Disabilities, Tokyo, JapanbDepartment of Pediatrics, Tokyo Women’s Medical University, School of Medicine, Tokyo, Japan

cDepartment of Neuroradiology, Tokyo Metropolitan Neurological Hospital, Tokyo, JapandDepartment of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan

Received 2 December 2002; received in revised form 19 March 2003; accepted 20 March 2003

Abstract

Brain magnetic resonance imaging was conducted in a girl with genetically confirmed spinal muscular atrophy (SMA) type I. This patient

has survived 6 years, to date, under mechanical ventilation. T2-weighted and fluid-attenuated inversion recovery images revealed high signal

intensity lesions in the anterolateral portions of the bilateral thalami. Electroencephalography disclosed diffuse beta activity upon awakening

and during light sleep. In addition, fast and prolonged spindles were observed. Although mild neuronal changes in the lateral nucleus of the

thalamus have been described in several autopsied cases, this is the first study to demonstrate neuroradiologically and neurophysiologically

the thalamic lesions in genetically confirmed SMA type I.

q 2003 Elsevier B.V. All rights reserved.

Keywords: Spinal muscular atrophy (SMA) type I; Magnetic resonance imaging (MRI); Electroencephalography (EEG); Thalamic lesions

1. Introduction

Spinal muscular atrophy (SMA) is an autosomal reces-

sive disorder. The responsible gene, the survival motor

neuron (SMN) gene, is located in chromosome 5q13 [1].

SMA is divided into three types [2,3]. SMA type I

(Werdnig–Hoffmann disease) is the most severe form,

with clinical onset before 6 months of age, and affected

individuals rarely survive beyond 2 years of age without

mechanical ventilation. The principal neuropathological

finding in SMA is degeneration of the anterior horn in the

spinal cord and the motor nuclei in the brainstem, but

neuropathological alterations have been described as

extending beyond the lower motor neurons. Iwata et al.

[4] and Shishikura et al. [5] noted neuronal changes, such as

chromatolysis, to commonly be observed in the thalamus

(particularly in the lateral nucleus) in SMA type I. However,

the clinical significance of these lesions has not yet been

clarified. Furthermore, since these pathological investi-

gations were conducted prior to identification of the SMN

gene, heterogeneous conditions may have been included.

Herein we conducted a brain magnetic resonance imag-

ing (MRI) study in a case of genetically confirmed SMA

type I, and for the first time radiologically demonstrated the

thalamic lesions.

2. Case report

2.1. Patient

The patient was a 6-year-old Japanese girl with SMA

type I who has been maintained on a ventilator, owing to

respiratory muscle weakness, since age 7 months. Her

mother aborted two fetuses, one spontaneously and the other

artificially. Her non-consanguineous parents and two

brothers are all in good health. She was born at term after

an uneventful pregnancy and weighed 3610 g at birth. There

was neither neonatal asphyxia nor difficulty in sucking or

0387-7604/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved.

doi:10.1016/S0387-7604(03)00075-5

Brain & Development 26 (2003) 53–56

www.elsevier.com/locate/braindev

* Corresponding author. Department of Pediatrics, Tokyo Women’s

Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku,

Tokyo 162-8666, Japan. Tel.: þ81-3-3353-8111; fax: þ81-3-5269-7338.

E-mail address: ymitoh@cf6.so-net.ne.jp (Y. Ito).

crying. She was capable of visual tracking and social

smiling within 2–3 months after birth. At 3 months of age,

she was examined for general hypotonia, poor head control,

and scant spontaneous movements. Fasciculation of the

tongue and absence of deep tendon reflexes, in addition to

neurogenic changes on electromyography (EMG), indicated

a diagnosis of SMA type I. Gene analysis confirmed homo-

zygous deletion of exons 7 and 8 in the telomeric SMN

gene. We repeatedly informed her family of the nature and

prognosis of the disease. They chose her prolonged survival

with a mechanical ventilation. She has been mechanically

ventilated all day since 7 months of age, for progressive

muscle weakness and respiratory failure. However, she has

suffered neither severe nor chronic hypoxic insults.

On physical examination, her height, weight and head

circumference were 105 cm, 8.7 kg, and 46 cm, respect-

ively. Her consciousness level and orientation were normal.

Considering her minimal social contacts and experiences,

and physical handicaps, she seemed to be above average in

intelligence, because she could communicate with her

family and nursing staff via movement of her eyes, fore-

head, eyelids, and the corners of her mouth, understood

many words, and responded to verbal commands. She is

currently completely bedridden. Head control was never

acquired. General muscle weakness and atrophy are appa-

rent. Her voluntary movements of the extremities are scant,

but she can move the MP joints of the thumb and index

finger against gravity and extend the elbow joints. Deep

tendon reflexes and superficial reflexes have both been lost.

Pathological reflexes are absent. There is no restriction of

ocular movements. Facial muscle weakness is relatively

mild and she can voluntarily move her forehead, eyelids,

and the corners of her mouth. In contrast, bulbar palsy is

severe and fasciculation is prominent in the tongue and

uvula. Neither superficial nor deep sensations are impaired.

2.2. Neuroradiological findings

Cranial computed tomography (CT) showed mild frontal

cortical atrophy and the cavum veli interpositi. Brain and

whole spinal cord MRI were performed under mechanical

ventilation while anesthesiologists managed the patient.

Brain MRI revealed high signal intensity lesions in the

anterolateral portions of the bilateral thalami on

T2-weighted and fluid-attenuated inversion recovery

(FLAIR) images (Fig. 1). High intensity areas were

recognized around the posterior horns of the lateral

ventricles on T2-weighted and FLAIR images, which may

represent terminal zones. There were no lesions in other

brain regions, including the whole spinal cord.

2.3. Electrophysiological findings

Electroencephalograms (EEG) were obtained upon

awakening and during natural sleep. Background activity

was composed of 50 – 75 mV, 11 Hz-alpha rhythms

predominantly in the occipital area. Diffuse superimposition

of 25–50 mV, 20–25 Hz fast waves was seen during both

awakening and sleep, though no sedatives had been

administered (Fig. 2A). During light sleep, symmetric and

organized spindles were observed in the frontocentral area,

but they were faster (16 Hz) than usual with prolonged

duration (Fig. 2B). No paroxysmal discharges were recog-

nized. Brainstem auditory evoked potentials and visual

evoked potentials were normal. Motor nerve and antidromic

sensory nerve conduction studies were performed. In the

median nerve, the amplitude of the compound muscle action

potential was markedly low (0.046 mV), but motor nerve

conduction velocity was within normal limits (41.0 m/s). No

compound muscle action potentials could be evoked in the

ulnar and tibial nerves. The amplitudes of sensory nerve

action potentials and sensory nerve conduction velocities in

the median, ulnar, and sural nerves were normal.

3. Discussion

In patients with SMA type I who survive on artificial

ventilation, it is usually considered an enormous challenge

to maintain an adequate quality of life. Thus, there is little

room for neurological evaluation. Generally, cranial CT and

MRI are not regarded as mandatory for making the

diagnosis of SMA, for which verification by genetic analysis

has recently become possible. Nevertheless, neuroradio-

logical and electrophysiological examinations will contri-

bute to understanding of the pathogenesis of SMA.

Previously, cranial CT showed cerebral atrophy, predomi-

nantly in the frontal lobe, in most patients with SMA type I

Fig. 1. Axial brain MRI. FLAIR image [TR/TE ¼ 10,002/158 ms]

revealing high signal intensity lesions in the anterolateral portions of the

bilateral thalami (arrowheads).

Y. Ito et al. / Brain & Development 26 (2003) 53–5654

[6,7]. Although such atrophy can result from repeated

hypoxic episodes [7], it was already present in the

first month of life and may have developed prenatally [6].

There have been only three reports on brain MRI in cases of

genetically confirmed SMA type I [8–10]. Mild cerebral

atrophy was found in a newborn case [8], possibly recon-

firming the aforementioned CT findings. One case in Hsu’s

report also showed brain atrophy at the age of 4 months [9].

An infant case showed severe cortical dysplasia with West

syndrome [10], although this seemed to be a rare and

exceptional coincidence. A long-surviving Japanese case of

SMA type I showed prominent white matter atrophy

including the corpus callosum in addition to diffuse cerebral

atrophy [11]. The thalamic lesions in our case have not, to

our knowledge, been described in previous reports.

Neuropathologically, the most important changes in

SMA type I are degeneration of the spinal and brainstem

motor neurons, which generally correlate with the clinical

course [3]. However, it is well known that the spinal

ganglion, posterior root, Clarke’s column, posterior funi-

culus and lateral thalamus are further affected. Thus, SMA

type I has been regarded as a multi-systemic disease also

involving sensory systems, despite the absence of clinical

sensory disturbances. Neuronal changes in the thalamus

have commonly been observed in SMA type I [4,5]. The

lateral thalamus usually reveals mild changes such as

central chromatolysis and/or neuronophagia, but without

apparent neuronal loss or gliosis. Nevertheless, oxidative

stress and disturbed glutamate transport can be demon-

strated even in the absence of severe neurodegeneration in

the lateral thalamus, suggesting latent thalamic changes

[12]. Accordingly, we speculate that the high signal

intensity lesions in the anterolateral portions of the thalamus

in our case may reflect established thalamic lesions

facilitated by the prolonged survival. It is noteworthy that

the intravital change in the thalamus was neuroradio-

logically identified in this genetically confirmed SMA

patient who has experienced neither severe nor chronic

hypoxia.

The rhythm of spindles and beta waves is thought to

originate in the thalamus [13,14]. Therefore, in this case, the

relationships between the thalamic lesions and EEG

abnormalities, consisting of diffuse beta activity during

both awakening and sleep, and fast and prolonged spindles,

are noteworthy. The reticular thalamic nucleus, which can

generate spindle rhythms, covers the rostral, lateral, and

ventral surfaces of the thalamus [13]. Furthermore, frontal

cortical atrophy can be related to involvement in the

thalamic motor nuclei (e.g. the ventral anterior nucleus and

ventral lateral nucleus), which are interconnected with the

primary motor cortex, prefrontal cortex, and supplementary

motor cortex [15]. The regional localization of MRI

thalamic lesions in our case strongly supports the involve-

ment of these nuclei.

Acknowledgements

We would like to thank Dr H. Nakayama, chief

anesthesiologist of Tokyo Metropolitan Neurological Hos-

pital, for the respiratory management at performing MRI.

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