214 J Neurol Neurosurg Psychiatry 1999;67:214–216 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.214 on 1 August 1999. Downloaded from
SHORT REPORT
Extrapyramidal involvement in amyotrophic lateral sclerosis: backward falls and retropulsion
Joy Desai, Michael Swash
Abstract functions were normal. There was no family Three patients with sporadic amyotrophic history of neurological illness. lateral sclerosis (ALS) presented with a General examination and vital indices were history of backward falls. Impaired pos- normal. There was no postural hypotension. tural reflexes and retropulsion accompa- There was a spastic dysarthria, and the palate nied clinical features of ALS. Hypokinesia, moved poorly. The jaw jerk was brisk and the decreased arm swing, and a positive glabel- tongue was wasted. Fasciculations were seen in lar tap were noted in two of these three the tongue and limb muscles. There was asym- patients. Cognitive impairment, tremor, metric wasting in the distal muscles of both axial rigidity, sphincter dysfunction, upper limbs. Power was 3/5 (MRC) distally, nuchal dystonia, dysautonomia, and oculo- and 4/5 proximally in the upper limbs. In the motor dysfunction were absent. Brain MRI legs, power was 4/5 in all muscles. Spasticity disclosed bilateral T2 weighted hyperinten- was found in all four limbs, with mild cogwheel sities in the internal capsule and globus rigidity at the wrists. There was hypokinesia of pallidus in one patient. Necropsy studies the face and posture. The speed of rapid rhyth- performed late in the course of ALS have mic finger and toe tapping was reduced but shown degeneration in extrapyramidal there was no rest tremor. Postural reflexes were sites—for example, the globus pallidus, impaired. When gently pulled backwards, even thalamus, and substantia nigra. Clinically, after a prior warning, he could not maintain backward falls and retropulsion may occur stability and toppled backwards. There was no early in ALS. This may reflect extrapy- adaptation to repetition of this manoeuvre. A ramidal involvement. gentle push on the chest resulted in a backward (J Neurol Neurosurg Psychiatry 1999;67:214–216) fall. He could maintain an upright stance and did not fall on being pushed forwards or later- Keywords: amyotrophic lateral sclerosis; backward falls; ally. All deep tendon reflexes were exaggerated retropulsion; globus pallidus and plantar responses were bilaterally extensor. http://jnnp.bmj.com/ HoVman’s sign was positive in both upper We found backward falls and retropulsion due limbs. The rest of the neurological assessment to postural instability early in the course of the was normal. The haematology, biochemistry, illness in three of a consecutive series of 22 erythrocyte sedimentation rate, immunoelec- patients with sporadic amyotrophic lateral trophoresis, thyroid functions, CSF, and MRI sclerosis (ALS). We report the clinical, labora- of the brain were normal. Nerve conduction tory, and neuro-imaging features and discuss studies were normal. Concentric needle EMG
the possible pathogenic basis of these extrapy- disclosed fasciculations, positive sharp waves, on October 6, 2021 by guest. Protected copyright. ramidal features. and evidence of chronic partial denervation with reinnervation in proximal and distal mus- The Department of cles of all four limbs. Neurology, The Royal One year later, upper limb strength had London Hospital, Case reports decreased to 3/5 (MRC). Power in the lower London E1 1BB, UK PATIENT 1 limbs had not changed although fasciculations J Desai A 60 year old man, previously well, developed were more obvious. Swallowing and speech M Swash slurred speech. He complained of stiVness in had deteriorated. Gentle forward and lateral both legs and frequent leg cramps. A month Correspondence to: pushes now resulted in uncontrolled falls, Professor Michael Swash, later while opening a door he fell backwards resistant to adaptation. There was more Department of Neurology, and incurred a minor scalp injury. Subse- The Royal London Hospital, marked hypokinesia and glabellar tap was posi- quently, he fell backwards twice while arising Whitechapel, London E1 tive. Cognition remained normal. The postural from a chair. He noticed frequent twitching of 1BB, UK. Telephone 0044 reflexes did not improve aftera6weektrialof 171 377 7472; fax 0044 171 muscles in his arms. Six months later, he 377 7318; email levodopa in a dose of 1 g/day. [email protected] developed diYculty in swallowing food and and [email protected] sometimes choked on drinks. He took an increasingly longer time to complete daily PATIENT 2 Received 9 November 1998 activities such as dressing and bathing. There A 65 year old woman presented with a 3 month and in revised form 20 January 1999 was no history of cognitive decline or tremor. history of stiVness and weakness of the right Accepted 24 January 1999 Sensory, sphincter, visual, and autonomic arm. She had diYculty in using the right hand Extrapyramidal involvement in amyotrophic lateral sclerosis 215 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.214 on 1 August 1999. Downloaded from
to open bottles, turn keys in locks, and to but- needle EMG disclosed profuse fasciculations ton clothes. She fatigued excessively. Five in both upper limbs and sporadic fasciculation months later she fell backwards while lifting a in the proximal muscles of the lower limbs. pot in her garden and on three further There was chronic partial denervation in both occasions she fell backwards while working in upper limbs and in proximal muscles of the her kitchen. She noted progressive weakness, lower limbs. Brain MRI showed bilateral T2 and wasting in the right hand with twitching of weighted hyperintensities in the internal cap- muscles in both arms and occasionally in the sule extending into the globus pallidus (figure). legs. Her speech slurred when she spoke quickly. Her medical history was unremark- PATIENT 3 able. Her mother had died aged 87 years with A 56 year old woman presented with a 5 month Alzheimer’s dementia. history of proximal weakness in the right arm. General examination was normal. Glabellar She noticed twitching of muscles in both arms. tap was positive. Her speech was slurred. The Her legs felt stiV and she walked more slowly. jaw jerk was brisk and palatal movements were She had a backward fall while opening her car normal. Lip smacking and tongue movements door and on three other occasions she fell in all directions were slow. Fasciculations were backwards in her garden while bending to trim noted in both arms and the left leg but not in a hedge. the tongue. There was wasting in the left The general examination and vital indices deltoid, triceps, and distal muscles of the right were normal. There was spasticity in all four hand and forearm. There was spasticity in all limbs. The deltoid and dorsal interossei four limbs with some cogwheel rigidity at the muscles were wasted. Fasciculations were wrists. Power was MRC 4/5 in the left upper visible in both arms and proximal muscles of limb and both lower limbs. In the proximal the legs. Power was MRC 3/5 in the deltoids, muscles of the right arm power was MRC 3/5 biceps, and brachioradialis bilaterally. In other and 2/5 to 1/5 in the distal muscles of the right muscles power was 4/5. In the distal muscles of hand. All the deep tendon reflexes were the lower limbs power was 5/5. The deep exaggerated and both plantar responses were tendon reflexes were brisk and both plantar extensor. HoVman’s sign was positive on the responses were extensor. Postural reflexes were left side. Postural reflexes were impaired. A impaired and retropulsion was easily elicited. gentle backward pull, after prior warning, There was no adaptation to repetition. There resulted in marked instability and an uncon- was no propulsion or lateropulsion. Cognition trolled backward fall. This did not adapt with and coordination were normal. repetition. Similar forward or lateral pushes did Haematology, biochemistry, erythrocyte not result in instability or falls. The gait was sedimentation rate, CSF, serum immunoelec- spastic, and arm swing was absent on the right. trophoresis, thyroid functions, and MRI of the There was no cognitive impairment or auto- brain were normal. Nerve conduction studies nomic dysfunction. were normal. Concentric needle EMG showed Haematology, biochemistry, thyroid func- fasciculations and positive sharp waves in the tion tests, erythrocyte sedimentation rate, upper limbs. There was chronic partial dener- serum immunoelectrophoresis, and CSF ex- vation with reinnervation in proximal and dis- amination were normal. Motor and sensory tal muscles of the upper limbs, and proximal
nerve conduction was normal. Concentric muscles of the lower limbs. http://jnnp.bmj.com/
Discussion Our patients fulfilled the Airlie House criteria (1998) for the diagnosis of ALS (
dysfunction, occurred early in the illness. Their on October 6, 2021 by guest. Protected copyright. postural reflexes were impaired and retropul- sion was a striking clinical feature. Brain MRI in patient 2 showed T2 weighted hyperintensi- ties in the internal capsule extending into the globus pallidus (figure). This probably reflects gliosis secondary to neuronal degeneration in these nuclei. Similar MRI features have been reported in Japanese patients with ALS.1 Striking impairment of postural reflexes resulting in backward falls occurs in progres- sive supranuclear palsy and multiple system atrophy. The absence of frontal lobe dysfunc- tion, dysautonomia, nuchal dystonia, and cerebellar and oculomotor dysfunction ruled out these diagnostic possibilities in our pa- tients. The pathophysiology of impairment of Axial T2 weighted MRI: hyperintense signal in the internal postural reflexes in disorders of the basal capsule extending into the globus pallidus. ganglia is complex.2 Martin suggested that in 216 Desai, Swash J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.214 on 1 August 1999. Downloaded from
“encephalitis lethargica” impairment of pos- in backward falls and retropulsion in three tural reflexes is attributable to degeneration in patients with sporadic ALS. The presence of the globus pallidus.34 A patient with carbon these extrapyramidal features should not invali- monoxide poisoning who had bilateral selective date a clinical diagnosis of ALS. damage to the globus pallidus, fell slowly back- wards on being gently tapped on the shoulder.5 1 Kato S, Hayashi H, Yagishita A. Involvement of the fronto- temporal lobe and limbic system in amyotrophic lateral Asymptomatic, subclinical degeneration in sclerosis: as assessed by serial computed tomography and the midbrain dopaminergic neurons has been magnetic resonance imaging. J Neurol Sci 1993; 116:52–8. shown by PET,67 and SPECT,8 in both 2 Bloem BR. Postural instability in Parkinson’s disease. Clin Neurol Neurosurg 1992;94(suppl):S41–5. sporadic and familial ALS. Degeneration in the 3 Martin JP. The basal ganglia and posture. London: Pittman, 1967. midbrain dopaminergic neurons has also been 4 Martin JP, Hurwitz LJ, Finlayson MH. The negative symp- detected in a transgenic mouse model of famil- toms of basal ganglia disease. Lancet 1962;ii:1, 62. 9 5 Haaxma R, van Boxtel A, Brouwer WH, et al. Motor ial ALS. Neurofibrillary tangles have been function in a patient with bilateral lesions of the globus pal- described in the globus pallidus, substantia lidus. Mov Disord 1995;10:761–77. 6 Takahashi H, Snow BJ, Bhatt MH, et al. Evidence of a nigra, and locus coeruleus of a patient with dopaminergic deficit in sporadic amyotrophic lateral ALS who had a point mutation at codon 113 in sclerosis on positron emission scanning. Lancet 1993;324: exon 4 of the SOD1 gene.10 Sporadic ALS with 1016–18. 7 Przedborski S, Dhawan V, Donaldson DM, et al. Nigrostri- widespread neuronal degeneration in the basal atal dopaminergic function in familial amyotrophic lateral ganglia, including the globus pallidus, has been sclerosis patients with and without copper/zinc superoxide dismutase mutations. Neurology 1996;47:1546–51. reported in Japan where survival is often 8 Borasio GD, Linke R, Schwarz J, et al. Dopaminergic deficit prolonged by assisted ventilation.11 12 Necropsy in amyotrophic lateral sclerosis assessed with [I-123] IPT single photon emission computed tomography. J Neurol studies are inevitably done late in the course of Neurosurg Psychiatry 1998;65:263–5. 9 Kostic V, Gurney ME, Deng HX, et al. Midbrain dopamin- the illness. In our patients with ALS, postural ergic neuronal degeneration in a transgenic mouse model instability, a feature of extrapyramidal involve- of familial amyotrophic lateral sclerosis. Ann Neurol ment, developed early in the illness. 1997;41:497–504. 10 Orrell RW, King AW, Hilton DA, et al. Familial amyotrophic Eisen and Calne suggested that parkinson- lateral sclerosis with a point mutation of SOD-1: ism, with or without dementia was associated intrafamilial heterogeneity of disease duration associated with neurofibrillary tangles. J Neurol Neurosurg Psychiatry with ALS at the same time in the course of the 1995;59:266–70. disease in 5% of cases.13 In chromosome 17 11 Iwanaga K, Hayashi S, Okaye M, et al. Neuropathology of sporadic amyotrophic lateral sclerosis of long duration. J associated frontotemporal dementia and Gua- Neurol Sci 1997;146:139–43. 12 Sasaki S, Tsutsumi Y, Yamane K, et al. Sporadic manian ALS, dementia of frontal lobe type, amyotrophic lateral sclerosis with extensive neurological parkinsonism, and ALS occur in varying com- involvement. Acta Neuropathologica 1992;84:211–15. 13 Eisen A, Calne D. Amyotrophic lateral sclerosis, Parkinson’s binations. However, dementia was not seen in disease and Alzheimer’s disease: phylogenetic disorders of our patients. Published reports of parkinson- the human neocortex sharing many characteristics. Can J ism associated with sporadic ALS have empha- Neurol Sci 1992;19:117–23. 14 Qureshi AI, Wilmot G, Dihenia B, et al. Motor neuron dis- sised the presence of rigidity, bradykinesia, ease with parkinsonism. Arch Neurol 1996;53:987–91. tremor, and gait disorder.14 15 We report the 15 Williams TL, Shaw PJ, Lowe J, et al. Parkinsonism in motor neuron disease: case report and literature review. Acta Neu- early impairment of postural reflexes resulting ropathologica 1995;89:275–83. http://jnnp.bmj.com/ on October 6, 2021 by guest. Protected copyright.