74274ournal ofNeurology, Neurosurgery, and Psychiatry 1995;58:742-744 SHORT REPORT J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.58.6.742 on 1 June 1995. Downloaded from Motor neuron disease (amyotrophic lateral sclerosis) arising from longstanding primary lateral sclerosis R P M Bruyn, J H T M Koelman, D Troost,J M B V de Jong Abstract family history was negative and consanguinity Three men were initially diagnosed as was excluded. Examination disclosed slight having primary lateral sclerosis (PLS), weakness of the left thigh muscles, mild spas- but eventually developed amyotrophic ticity of the legs, knee and ankle cloni, and lateral sclerosis (ALS) after 7-5, 9, and at extensor plantars. Blood chemistry, CSF, and least 27 years. Non-familial ALS and EMG were unremarkable. Magnetic reso- PLS might be different manifestations of nance imaging of the cervical spine was nor- a single disease or constitute completely mal and PLS was diagnosed. Micturition distinct entities. The clinical diagnosis of urgency began in 1987. Examination in 1988 PLS predicts a median survival that is showed definite spastic paraparesis and mild four to five times longer than in ALS. proximal weakness of the legs. Sural and tib- ial nerve somatosensory evoked potentials (J Neurol Neurosurg Psychiatry 1995;58:742-744) (SSEPs) were bilaterally absent and delayed respectively. Visual and brainstem auditory evoked potentials (VEPs, BAEPs), and brain Keywords: amyotrophic lateral sclerosis; primary MRI were normal. By 1990, walking had lateral sclerosis become troublesome and dysarthria was pre- sent; the calves showed fasciculation and Primary lateral sclerosis (PLS), defined as some atrophy. The left extensor hallucis mus- non-familial progressive spinobulbar or bul- cle was paralytic and the right comeo- bospinal spasticity-without amyotrophy, fas- mandibular reflex was now positive. During ciculation, optic atrophy, deafness, or pedes 1991 and 1992 dysarthria, forced laughter, cavi and with no more pronounced sphinc- and generalised weakness progressed and ter disturbances than urgency of micturition, amyotrophy became evident. Examination and not caused by a segmental lesion, is rare. now disclosed widespread fasciculation of http://jnnp.bmj.com/ Its status as a nosological entity, separate trunk and limb muscles, considerable amy- from the hereditary spastic paraplegias on the otrophy, most pronounced in the lower legs, one hand and amyotrophic lateral sclerosis and brisk masseter and bilaterally positive (ALS) on the other, remains disputed. comeomandibular reflexes. The diagnosis Mulder' suggested that ALS begins with was changed to that of ALS. Repeat EMG in peripheral weakness, and Pringle and cowork- 1993 showed very low compound muscle ers PLS on initial central motor action potentials (CMAPs) of the intrinsic Department of diagnose on September 30, 2021 by guest. Protected copyright. Neurology, Oudenryn deficit.2 foot muscles bilaterally. Denervation activity Hospital, Utrecht, The Gowers described the first patients with seemed limited to the anterior tibial muscles, Netherlands progressive spastic paraparesis, eventually whereas re-innervation activity was seen in R P M Bruyn complicated by amyotrophy.3 Spiller reported the limb musculature. The patient continues Department of to deteriorate slowly. Neurology eight patients of whom bulbar or limb spas- J G T M Koelman ticity was the initial sign.4 This was followed J M B V de Jong by lower motor signs in six, but remained as CASE 2 Department of the only sign in two. Wilson' and Brouwer6 In 1983, at the age of 39, a previously healthy Pathology, Graduate claimed to have seen similar patients with a plumber noticed slurring of speech. The School of was no consanguinity Neurosciences long standing spastic paraparesis eventually family history negative; Amsterdam, followed by wasting in the hands. was present. Examination of this otherwise Academic Medical Our three patients (one with a necropsy) healthy right handed man of athletic build Centre, Amsterdam, disclosed minimal dysarthria, increased ten- The Netherlands demonstrate that longstanding PLS may D Troost change into ALS. don jerks, and positive comeomandibular Correspondence to: reflexes. Physical examination and extensive Dr RPM Bruyn, study of blood chemistry and CSF were unre- Department of Neurology, were nor- Oudenryn Hospital, 1 van Case reports markable. An EEG and brain CT Heuven Goedhartlaan, 3527 CASE 1 mal. No definite diagnosis was made. In CE Utrecht, The Netherlands. In 1984, at the age of 45, a previously healthy 1984, the patient developed a mild right Received 1 November 1994 manager experienced trouble in maintaining sided hemiparesis and ankle cloni. Spastic and in revised form and noticed slowly progressive paraparesis and extensor plantars became evi- 16 February 1995. his balance, Accepted 24 February 1995 stiffness of the left leg with cramps. The dent in 1985. Sural and tibial nerve SSEPs Motor neuron disease (amyotrophic lateral sclerosis) arisingfrom longstanding primary lateral sclerosis 743 were bilaterally absent; median nerve SSEPs was seen in the distal and proximal limb J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.58.6.742 on 1 June 1995. Downloaded from and EMG were normal and PLS was diag- muscles. nosed. In 1989, atrophy of the interosseous The diagnosis was changed from PLS to hand muscles became apparent, with fascicu- ALS. The course remains slowly progressive. lation of wrist and finger extensors. Sensation remained intact. Electromyography showed CASE 3 signs of re-innervation but no evidence of In 1957, a 33 year old office clerk was admit- denervation. Conduction velocities were nor- ted for analysis of a heavy feeling in his legs mal. Magnetic resonance imaging showed and cramps in the calves and proximal leg some thinning of the cervical cord but no muscles, progressive complaints that had brain abnormalities. Amyotrophy spread to begun at the age of 27. There was no consan- involve the forearms and eventually the lower guinity and the family history was negative. legs. Repeat EMG in 1991 disclosed fibrilla- On admission, hyperreflexia of arms and legs tion and positive sharp waves in the left ante- was found with a patellar clonus, and a left rior tibial muscle; in 1993 very low CMAPs extensor plantar sign; CSF was normal and of the extensor digitorum communis muscles PLS was diagnosed. His condition deterio- were noted, as well as denervation activity in rated very slowly. Examination in 1978 both tibial anterior muscles, the rectus showed moderate spasticity of both legs, knee femoris, and the first interosseous muscle, and ankle clonus, Babinski signs, and a with fasciculations. Re-innervation activity slightly decreased vibration sense at the ankles. Fasciculations or atrophy were not present. Cervical myelography was normal. Electromyography showed decreased conduc- tion velocities of both peroneal nerves with no denervation activity. The patient was lost to follow up but was necropsied in 1989, having died of pneumonia. There were no gross alterations to the brain. The spinal cord and the anterior roots showed mild atrophy. Microscopy showed a severe loss of spinal anterior horn cells, a subtotal at the dorsolumbar and mild at the cervicodorsal level. Mild cell loss was noted in Clarke's columns. Numerous amylaceous bodies and occasional instances of neuronophagia with considerable reactive gliosis were evident throughout the cord. A pronounced myelin pallor characterised the pyramidal tracts. Macrophages and acti- vated microglial cells immunocytochemically stained with Tal 1 B5 (MHC common frame- work antigen) antibody (Bodmer; dilution http://jnnp.bmj.com/ 1:20) on paraffin slides (for method see van den Bergh et a17) were strongly positive in the Figure 1 Spinal cord at level C7. Widespread immunoreactivity for MHC common framework antigen is present in lateral and anterior columns. There is mild staining in the entire spinal cord (figs 1 and 2), except the anterior horns (bar represents 1 5 mm). posterior funiculi. Lymphocytic infiltration was not present. The diagnosis was changed to ALS. C. on September 30, 2021 by guest. Protected copyright. b~~s:'^* t Discussion The El Escorial diagnostic criteria8 for ALS ;t include both upper (spasticity, hyperreflexia, extensor plantar signs, increased gag and lr* snout reflexes, and pseudobulbar effect) and lower (asymmetric weakness, atrophy, fascic- "'Xw. 4 ulation) motor neuron signs. The onset is 1,*'~ ~ X insidious, its course invariably progressive, usually without sensory involvement (although sensory pathways may be & E,*~~~~~~~~f r affected9 10), and survival is inversely related b-'4O X d * A to age at diagnosis." 12 Clinical diagnostic cri- teria for PLS include an insidious adult onset C* *S_s - tY', . of spastic paresis, usually beginning in the e,d, v S legs, without a family history, running a slowly progressive course of at least three } ;;Q. f ~.sAs.44's 9 d years, ultimately leading to a severe spastic ts _d spinobulbar paresis, and atrophy of the pre- central gyrus on MRI.' Figure 2 Numerous cells in the white matter of the spinal cord expressing MHC common The debate-whether PLS is a distinct framework antigen (bar represents 70 pm). nosological entity or a forme fruste of ALS- 744 Bruyn, Koelman, Troost, de J7ong is still going on. According to Mackay,'3 PLS tetraparesis, and spinobulbar paresis'9 will J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.58.6.742 on 1 June 1995. Downloaded from is simply ALS without lower motor neuron remain a diagnostic challenge. signs, which are bound to appear unless death To avoid unnecessary distress to patients, supervenes. In his series of 70 deceased retention of the diagnosis of PLS may be jus- patients with ALS 11 presented with purely tified, because of its favourable prognosis spastic features for several years before mus- compared with ALS with lower motor neuron cle atrophy became manifest. Only one onset. patient remained purely spastic until death. He excluded three patients, alive at the time of study, who had had purely spastic paresis for as long as 21 years.