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Recessively inherited ‘pure’ spastic paraplegia: Case study
Case reports RECESSIVELY INHERITED 'PURE' SPASTIC PARAPLEGIA: CASE STUDY I. F. M. de Coo*, F. J. M. Gabre~ls*, W. O. Renier*, E. J. Colon** and B. G. A. ter naar***
SUMMARY Two brothers with 'pure' spastic paraplegia are presented. Inheritance of their condition probably was autosomal recessive. Clinical onset was in the first decade. Peripheral nerve conduction, visual and brain stem auditory evoked potentials were normal. Somatosensory evoked potentials suggested involvement of the cuneate tract. The relevance of neurophysiological evaluation in familial spastic paraplegia is discussed.
INTRODUCTION
Familial spastic paraplegia (FSP) is a progressive neurological disorder with autosomal dominant (Striampell-Lorrain disease), autosomal recessive (ERB, 1895) or X-linked (T.URMON et al., 1971) inheritance. In its 'pure' form the condition is characterized by progressive weakness and spasticity predominantly of the lower limbs, in the absence of associated neurological features other than discrete disturbances of gnostic sensation (BEHAN and MAIA, 1974; HOLMESand SHAYWITZ, 1977). Autosomal recessive inheritance in the 'pure' form is apparently rare since only 15 sufficiently documented families with a total of 41 patients have been reported to date. We here describe two brothers with 'pure' FSP, probably inherited by autosomal recessive transmission.
* Institute of Neurology, Department of Child Neurology, ** Institute of Neurology, Department of Clinical Neurophysiology, *** Institute of Pediatrics, Radboud University Hospital, Nijmegen, The Netherlands Clin. Neurol. Neurosurg. 1982 Vol. 84-4 (Accepted 17-11-82).
248 CASE REPORTS
For the pedigree see Fig. 1.
2
2
2
3
3
2
2
Fig. 1. The pedigree of our patients with AR 'pure' spastic paraplegia. Numbers below box or circle indicate number of offspring.
CASE 1
This boy was the first child of non-consanguineous parents. Pregnancy and delivery were uneventful. Birth weight was 4,200 g. Retardation of motor development became manifest from his second year, and progressed slightly with age. On examination at the age of 16 he could walk reasonably well, despite moderate spastic paraplegia of the legs. There was bilateral pes cavus deformity. The arms were normal. There was no muscular atrophy. Sensation was normal. Tendon reflexes were exaggerated. Plantar responses were extensor. Abdominal and cremasteric reflexes were positive. No other neurological dysfunction was found. CASE 2
This younger brother of case 1 was born without complications after an uneventful pregnancy. Birth weight was 3,300 g. At 18 months he was noticed to walk 'clumsily'. Examination at 5 years revealed slight paresis of the legs, without hypertonia or atrophy. The reflexes were exaggerated and an extensor plantar response was present. Abdominal and cremasteric reflexes were positive. No other neurological dysfunction was found. Biopsy of the sural nerve revealed no abnormalities on light and electron microscopical examination. At the age of 14 he still could walk quite well. Examination then revealed distinct hypertonia with moderate paresis of the legs. Muscles of the lower legs were slightly atrophic. There was bilateral pes cavus deformity. The arms were normal. Tendon reflexes were hyperactive with clonus. Plantar responses were extensor. Abdominal and cremasteric reflexes were positive. Sensation was normal. No other neurological dysfunction was found. Neurological examination of the parents revealed no abnormalities, included no
249 pes cavus deformity. Likewise, no neurological abnormalities were mentioned in the families of either parent. LABORATORY INVESTIGATIONS
Standard blood and urinary studies, including hematological evaluation, renal and hepatic functions, serum protein and serum protein electrophoresis, were normal. Appropriate studies gave normal values for: thiamine, pyridoxine, cobalamine, folate, toxoplasmosis, syphilis, mercury, lead, arsenic, thallium, calcium, phosphorus, T 3, T 4, cortisone rhythm, pyruvate, lactate, fructose, galactose, L alanine loading test, serum copper, ceruloplasmin, acid mucopolysaccharides, uric acid, amino acids, organic acids, lysosomal enzymes, serum lipids, cholesterol, triglycerides and short chain fatty acids. Studies on cerebrospinal fluid (CSF) showed a normal white cell count, protein, protein electrophoresis and immunoelectrophoresis, glucose, lactate, pyruvate and ketone bodies. RADIOLOGICALINVESTIGATIONS CT scans showed no abnormalities. NEUROPHYSIOLOGICAL INVESTIGATIONS
EEG and EMG revealed no abnormalities. Motor and sensory nerve conduction was normal in the upper and lower limbs. Brain stem auditory evoked potentials (BAEP) and pattern reversal visual evoked potentials (PRVEP) were within normal limits. Somatosensory evoked potentials (SSEP) on stimulation of the index finger (COLON et al., 1979) showed increased latency of the main negative peak of the cervical response (recorded at C 7) and increased latency of the early cortical response (Table 1). Interval between the two responses was normal. Latency of the early cortical response to stimulation of the sural nerve was normal (Table 1). Late components of the cortical SSEP were within normal limits. DISCUSSION
Since the first description of FSP there has been continuous discussion as to how this syndrome should be classified. Usually the syndrome is classified in the group of spinocerebellar degenerations (GREENFIELD, 1954). The precise nosologic classification of the syndrome, however, is still difficult to establish since the association with a number of other features, such as amyotrophy, sensory neuropathy, optic atrophy, nystagmus and extrapyramidal signs (BOBOWICgand BRODY, 1975), suggests that the syndrome, rather than being one single disease entity, presents a very heterogenous group of disorders. SCHWARZ and LIU (1956) and BEHAN and MAIA (1974) were convinced, on the basis of post-mortem findings, that FSP represents a separate clinico-pathological entity. The common feature in post-
250
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251 30.
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F%a 10 2'0 3'0 40 50 Age of onset ( y e a r s )
6'o
Fig. 2. Histogram illustratingrange of age of onset in published cases with AR 'pure' spastic paraplegia.
mortem studies (NEWMARK,1906; BEHANand MAIA, 1974; FISHER, 1977; SACKet al., 1978), all of which refer to the autosomal dominant form, is bilateral retrograde degeneration (dying back) of the crossed corticospinal pathways. To a lesser degree, the uncrossed corticospinal tracts are also involved (BUGEet al., 1979). Furthermore, dying back of the centrally directed axons of spinal ganglion cells occurs with the posterior columns (particularly within the fasciculus gracilis). Posterior root fibers, cortex and brain stem are not involved. The two brothers presented by us suffer from a 'pure' form of spastic paraplegia, without any other associated neurological symptoms. Pedigree (Fig. l) suggests that inheritance of their condition is autosomal recessive (AR), though autosomal dominant (AD) or X-linked inheritance cannot be entirely ruled out. Age at onset in the AR variety is illustrated in Fig. 2. The age distribution in this figure suggests the possibility of three sub-types with (late) infantile, juvenile or adult onset respectively. As in the majority of AR cases, clinical onset in our patients was in the first decade. In addition, there was intrafamilial homochrony (onset within the same decade), which is another typical feature of the AR form. The AR variety resembles the AD type with regard to severity of the symptoms (HOLMESand SHAYWlTZ, 1977), but differs in the usually earlier onset and the strong intrafamilial homochrony. Comparison with the X-linked type is difficult since only very few X-linked cases have been described (ZAIZ et al., 1976). BAEP and PRVEP in our patients were normal. The latter finding does not confirm the PRVEP studies by ROTHSCHILDet al. (1979), HAPPELet al. (1980) and BIRD and CRILL (1981), which suggested that involvement of the optic pathway is common in FSP. In another PRVEP study (LIVINGSTONEe l al., 198 l), abnormalities were found in only a minority of studied FSP patients. The question arises, however, whether FSP patients with abnormal PRVEP (or BAEP) can still be considered as 'pure' cases. This particularly applies to the reported cases with atypical features (lower cranial nerve involvement, unusual time of onset) in addition to abnormal PRVEP.
252 SSEP study in our patients (Table 1) revealed delayed transmission from index finger to brain stem (increased latency of the main negative peak of the cervical SSEP, which is speculatively assigned to the brain stem nuclei of Goll and Burdach or the medial lemniscus), with normal transmission from brain stem to cortex. Since delayed transmission distally to the spinal ganglia was excluded by peripheral nerve conduction study, by inference the delay must originate between the dorsal roots (which are known to be preserved in FSP: BEHAN and MAIA, 1974) and the brain stem, i.e. in the cuneate tract. Transmission in the tractus gracilis was normal (normal latency of the early cortical response to stimulation of the sural nerve). These observations further support the concept (THOMASet al., 1981 ) that in FSP the centrally directed axons of spinal ganglion cells may degenerate within the posterior columns, while the peripherically directed axons in the peripheral nerves remain intact. An unexplained finding in our cases is the apparently selective involvement of the cuneate tract, whereas post-mortem studies have usually revealed the entire posterior column to be affected (NEWMARK, 1906; BEHAN and MAIA, 1974: BUttE el al., 1979). In our view, evoked potential study in FSP provides a useful aid in separating the 'pure' form (in which SSEP evidence for posterior column involvement may appear to be a regular feature) from varieties with additional involvement of visual or auditory pathways. By making the 'pure' group as homogenous as possible, further investigations into its etiology will become more fruitful.
AC K N O W L E D G E M E N T S
Gratitude is extended to Dr. A. A. W. M. Gabreels-Festen for morphological investigation, to Dr. A. J. L. Pinckers for pattern reversal visual evoked potentials, and to Mr. M. Hoekstra for brain stem auditory evoked potentials. REFERENCES BEnAN. W. M. n. and M. MAla (1974) Str0mpell's familial spastic paraplegia: genetics and neuropatholo~y. J. Neurol. Neurosurg. Psvchiat. 37:8. BIRD, 1. D. and w. E. CRILL (1981) Pattern-reversal visual evoked potentials in the hereditary ataxias and spinal degenerations. Ann. Neurol. 9:243, BO~OWI('K, A. R. and J. A. BRODV (1975) Epidemiolog v of neurodegenerative system disorders. In: Vinkem P. J. and G. W. Bruyn (Eds). Handbook of Clinical Neurologv. North-Holland, Amsterdam, Vol. 21:3. BUGE, A., R. ESCOUROLLE, G. RANCUREL, F. GRAY anO B, F. PERTUISET (1979) La paraplegie spasmodique familiale de Strt~mpell-Lorrain (P.S.F.) Une nouvelle observation anatomo-clinique. Rev. Neurol. (Paris) 135:329. COLON, E,, W. RENtE~ and v. GABREICLS(1979) Propagation defects in somatosensor v evoked responses in children. In: Lechner, H. and A. Aranibar (Eds). EEG and Clin. Neurophys. Elsevier, North-Holland,Amsterdam, 526:306. ER~, w. (1895) Ueber heredit~ire spastische Spinalparalyse. Dtsch. Z. Nervenheilk. 6:137. HSrtER, C. M. (1977) Pure spastic paralysis of corticospinal origin. Canad. J. Neurol. Sci. 4:251. GREENFtELD, J. G. (1954) The spinocerebellar degenerations. Blackwell, Oxford. HAPPEL, L. T., H. ROTHSCHILD and c. GARCIA (1980) Visual evoked potentials in two forms of hereditary spastic paraplegia. Electroencephalogr. Clin. Neurophysiol. 48:233.
253 HOLMES, G. L. and a. A. SHAYWITZ (1977) Strumpell's pure familial spastic paraplegia: case study and review of the literature. J. Neurol. Neursosurg. Psychiat. 40: 1003. LIVINGSTONE, I. R., F. L. MASTAGLIA, R. EDIS and J. w. HOWE (1981) Pattern visual evoked responses in hereditary spastic paraplegia. J. Neurol. Neursorug. Psychiat. 44:176. NEWMARK,L. (1906) Pathologisch-anatomischer Befund in einem weiteren Falle von famili~irer spastischer Paraplegie. Dtsch. Z. Nervenheilk. 31:224. ROTHSCHILD, H., L. HAPPEL, D. RAMPP and E. HACKETT (1979) Autosomal recessive spastic paraplegia: evidence for demyelination. Clin. Genet. 15:356. SACK JR., G.H., C. A. HUETHER and N. GARG (1978) Familial spastic paraplegia-Clinical and pathologic studies in a large kindred. Johns Hopkins Med. J. 143:117. SCHWARL G. A. and C.-N. LIU (1956) Hereditary (familial) spastic paraplegia. Further clinical and pathologic observations. Arch. Neurol. Psychiat. 75:144. THOMAS, P. K., J. G. R. JEFFERYS, 1. S. SMITH and D. LOULAKAKIS(1981) Spinal somatosensory evoked potentials in hereditary spastic paraplegia. J. Neurol. Neurosurg. Psychiat. 44:243. THURMON, T. F., B. A. WALKER,C. I. SCOTTand M. H. ABBOTH(1971) Two kindreds with a sex-linked recessive form of spastic paraplegia. In: The clinical delineation of birth defects. Williams and Wilkins, Baltimore~ Vol. 6:219. ZATZ. M., C. PENHA-SERRANOand a. A. OTTO (1976) X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg. J. Med. Genet. 13:217.
LIST OF PUBLICATIONS ABOUT PATIENTS WITH RECESSIVELY INHERITED PURE SPASTIC PARAPLEGIA SCH~LE, A. (1893) Die Lehre yon der spastischen Spinalparalyse. Dtsch. Z. Nervenheilk. 4:161. ERB, W. (1895) Ueber heredit~ire spastische Spinalparalyse. Dtsch. Z. Nervenheilk. 6:137. KRAFT-EBBING, R. (1900) Ueber infantile famili~ire spastische Spinalparalyse. Dtsch. Z. Nervenheilk. 17:87. JONES, E. (1907) Eight cases of hereditary spastic paraplegia. Rev. Neurol. Psychiat. 5:98. SCHULTZE, F. (1926) Zur Lehre v o n d e r spastischen Gliederstarre und der sogenannten 'spastischen spinalen Paralyse'. Dtsch. Z. Nervenheilk. 92:161. ULLA, J. (1945) Un caso de presentation familiar de paralisi espinal espasmodica. Med. Madrid 13:435. FREUND, J. (1949) Crber spastische Spinalparalyse (Strtimpell) bei einem Brtiderpaar. Dtsch. Z. Nervenheilk. 161:337. RITTER, S. (1959) Au sujet de la parapar6sie spastique familiale de Strumpell. Zhurnal Neuropatologii i Psikhiatrii Imeni S.S. Korsakova (Moskva) 59:525. OZSV/kTH, K. (1968) Paralysis spinalis spastica familiaris. Dtsch. Z. Nervenheilk. 193:287. MEYER, D. W. and H. C. HOPF (1971) Beobachtungen tiber die adulte Form der recessiv-erblichen spastischen Spinalparalyse. Z. Neurol. 199:256. MCLEOD, J. G., J. A. MORGAN and c. REYE(1977) Electrophysiological studies in familial spastic paraplegia. J. Neurol. Neurosurg. Psychiat. 40:611. VERNEA,J. and G. R. SYMINGTON (1977) The late form of pure familial spastic paraplegia. Proc. Aust. Assoc. Neurol. Vol. 14:37. HARDING, A. E. (1981) Hereditary 'pure' spastic paraplegia: a clinical and genetic study of 22 families. J. Neurol. Neurosurg. Psychiat. 44:87 I.
SUMMARY Two brothers with 'pure' spastic paraplegia are presented. Inheritance of their condition probably was autosomal recessive. Clinical onset was in the first decade. Peripheral nerve conduction, visual and brain stem auditory evoked potentials were normal. Somatosensory evoked potentials suggested involvement of the cuneate tract. The relevance of neurophysiological evaluation in familial spastic paraplegia is discussed.
INTRODUCTION
Familial spastic paraplegia (FSP) is a progressive neurological disorder with autosomal dominant (Striampell-Lorrain disease), autosomal recessive (ERB, 1895) or X-linked (T.URMON et al., 1971) inheritance. In its 'pure' form the condition is characterized by progressive weakness and spasticity predominantly of the lower limbs, in the absence of associated neurological features other than discrete disturbances of gnostic sensation (BEHAN and MAIA, 1974; HOLMESand SHAYWITZ, 1977). Autosomal recessive inheritance in the 'pure' form is apparently rare since only 15 sufficiently documented families with a total of 41 patients have been reported to date. We here describe two brothers with 'pure' FSP, probably inherited by autosomal recessive transmission.
* Institute of Neurology, Department of Child Neurology, ** Institute of Neurology, Department of Clinical Neurophysiology, *** Institute of Pediatrics, Radboud University Hospital, Nijmegen, The Netherlands Clin. Neurol. Neurosurg. 1982 Vol. 84-4 (Accepted 17-11-82).
248 CASE REPORTS
For the pedigree see Fig. 1.
2
2
2
3
3
2
2
Fig. 1. The pedigree of our patients with AR 'pure' spastic paraplegia. Numbers below box or circle indicate number of offspring.
CASE 1
This boy was the first child of non-consanguineous parents. Pregnancy and delivery were uneventful. Birth weight was 4,200 g. Retardation of motor development became manifest from his second year, and progressed slightly with age. On examination at the age of 16 he could walk reasonably well, despite moderate spastic paraplegia of the legs. There was bilateral pes cavus deformity. The arms were normal. There was no muscular atrophy. Sensation was normal. Tendon reflexes were exaggerated. Plantar responses were extensor. Abdominal and cremasteric reflexes were positive. No other neurological dysfunction was found. CASE 2
This younger brother of case 1 was born without complications after an uneventful pregnancy. Birth weight was 3,300 g. At 18 months he was noticed to walk 'clumsily'. Examination at 5 years revealed slight paresis of the legs, without hypertonia or atrophy. The reflexes were exaggerated and an extensor plantar response was present. Abdominal and cremasteric reflexes were positive. No other neurological dysfunction was found. Biopsy of the sural nerve revealed no abnormalities on light and electron microscopical examination. At the age of 14 he still could walk quite well. Examination then revealed distinct hypertonia with moderate paresis of the legs. Muscles of the lower legs were slightly atrophic. There was bilateral pes cavus deformity. The arms were normal. Tendon reflexes were hyperactive with clonus. Plantar responses were extensor. Abdominal and cremasteric reflexes were positive. Sensation was normal. No other neurological dysfunction was found. Neurological examination of the parents revealed no abnormalities, included no
249 pes cavus deformity. Likewise, no neurological abnormalities were mentioned in the families of either parent. LABORATORY INVESTIGATIONS
Standard blood and urinary studies, including hematological evaluation, renal and hepatic functions, serum protein and serum protein electrophoresis, were normal. Appropriate studies gave normal values for: thiamine, pyridoxine, cobalamine, folate, toxoplasmosis, syphilis, mercury, lead, arsenic, thallium, calcium, phosphorus, T 3, T 4, cortisone rhythm, pyruvate, lactate, fructose, galactose, L alanine loading test, serum copper, ceruloplasmin, acid mucopolysaccharides, uric acid, amino acids, organic acids, lysosomal enzymes, serum lipids, cholesterol, triglycerides and short chain fatty acids. Studies on cerebrospinal fluid (CSF) showed a normal white cell count, protein, protein electrophoresis and immunoelectrophoresis, glucose, lactate, pyruvate and ketone bodies. RADIOLOGICALINVESTIGATIONS CT scans showed no abnormalities. NEUROPHYSIOLOGICAL INVESTIGATIONS
EEG and EMG revealed no abnormalities. Motor and sensory nerve conduction was normal in the upper and lower limbs. Brain stem auditory evoked potentials (BAEP) and pattern reversal visual evoked potentials (PRVEP) were within normal limits. Somatosensory evoked potentials (SSEP) on stimulation of the index finger (COLON et al., 1979) showed increased latency of the main negative peak of the cervical response (recorded at C 7) and increased latency of the early cortical response (Table 1). Interval between the two responses was normal. Latency of the early cortical response to stimulation of the sural nerve was normal (Table 1). Late components of the cortical SSEP were within normal limits. DISCUSSION
Since the first description of FSP there has been continuous discussion as to how this syndrome should be classified. Usually the syndrome is classified in the group of spinocerebellar degenerations (GREENFIELD, 1954). The precise nosologic classification of the syndrome, however, is still difficult to establish since the association with a number of other features, such as amyotrophy, sensory neuropathy, optic atrophy, nystagmus and extrapyramidal signs (BOBOWICgand BRODY, 1975), suggests that the syndrome, rather than being one single disease entity, presents a very heterogenous group of disorders. SCHWARZ and LIU (1956) and BEHAN and MAIA (1974) were convinced, on the basis of post-mortem findings, that FSP represents a separate clinico-pathological entity. The common feature in post-
250
¢xl
6 e,
4,
e.!
¢.i
_'2 o
~5
6. v-
A o.
,'.
o
,4
o
c~E~
v~
m
- ~
-.2 t~
a ~ .~
251 30.
2(2, ,j
10,
F%a 10 2'0 3'0 40 50 Age of onset ( y e a r s )
6'o
Fig. 2. Histogram illustratingrange of age of onset in published cases with AR 'pure' spastic paraplegia.
mortem studies (NEWMARK,1906; BEHANand MAIA, 1974; FISHER, 1977; SACKet al., 1978), all of which refer to the autosomal dominant form, is bilateral retrograde degeneration (dying back) of the crossed corticospinal pathways. To a lesser degree, the uncrossed corticospinal tracts are also involved (BUGEet al., 1979). Furthermore, dying back of the centrally directed axons of spinal ganglion cells occurs with the posterior columns (particularly within the fasciculus gracilis). Posterior root fibers, cortex and brain stem are not involved. The two brothers presented by us suffer from a 'pure' form of spastic paraplegia, without any other associated neurological symptoms. Pedigree (Fig. l) suggests that inheritance of their condition is autosomal recessive (AR), though autosomal dominant (AD) or X-linked inheritance cannot be entirely ruled out. Age at onset in the AR variety is illustrated in Fig. 2. The age distribution in this figure suggests the possibility of three sub-types with (late) infantile, juvenile or adult onset respectively. As in the majority of AR cases, clinical onset in our patients was in the first decade. In addition, there was intrafamilial homochrony (onset within the same decade), which is another typical feature of the AR form. The AR variety resembles the AD type with regard to severity of the symptoms (HOLMESand SHAYWlTZ, 1977), but differs in the usually earlier onset and the strong intrafamilial homochrony. Comparison with the X-linked type is difficult since only very few X-linked cases have been described (ZAIZ et al., 1976). BAEP and PRVEP in our patients were normal. The latter finding does not confirm the PRVEP studies by ROTHSCHILDet al. (1979), HAPPELet al. (1980) and BIRD and CRILL (1981), which suggested that involvement of the optic pathway is common in FSP. In another PRVEP study (LIVINGSTONEe l al., 198 l), abnormalities were found in only a minority of studied FSP patients. The question arises, however, whether FSP patients with abnormal PRVEP (or BAEP) can still be considered as 'pure' cases. This particularly applies to the reported cases with atypical features (lower cranial nerve involvement, unusual time of onset) in addition to abnormal PRVEP.
252 SSEP study in our patients (Table 1) revealed delayed transmission from index finger to brain stem (increased latency of the main negative peak of the cervical SSEP, which is speculatively assigned to the brain stem nuclei of Goll and Burdach or the medial lemniscus), with normal transmission from brain stem to cortex. Since delayed transmission distally to the spinal ganglia was excluded by peripheral nerve conduction study, by inference the delay must originate between the dorsal roots (which are known to be preserved in FSP: BEHAN and MAIA, 1974) and the brain stem, i.e. in the cuneate tract. Transmission in the tractus gracilis was normal (normal latency of the early cortical response to stimulation of the sural nerve). These observations further support the concept (THOMASet al., 1981 ) that in FSP the centrally directed axons of spinal ganglion cells may degenerate within the posterior columns, while the peripherically directed axons in the peripheral nerves remain intact. An unexplained finding in our cases is the apparently selective involvement of the cuneate tract, whereas post-mortem studies have usually revealed the entire posterior column to be affected (NEWMARK, 1906; BEHAN and MAIA, 1974: BUttE el al., 1979). In our view, evoked potential study in FSP provides a useful aid in separating the 'pure' form (in which SSEP evidence for posterior column involvement may appear to be a regular feature) from varieties with additional involvement of visual or auditory pathways. By making the 'pure' group as homogenous as possible, further investigations into its etiology will become more fruitful.
AC K N O W L E D G E M E N T S
Gratitude is extended to Dr. A. A. W. M. Gabreels-Festen for morphological investigation, to Dr. A. J. L. Pinckers for pattern reversal visual evoked potentials, and to Mr. M. Hoekstra for brain stem auditory evoked potentials. REFERENCES BEnAN. W. M. n. and M. MAla (1974) Str0mpell's familial spastic paraplegia: genetics and neuropatholo~y. J. Neurol. Neurosurg. Psvchiat. 37:8. BIRD, 1. D. and w. E. CRILL (1981) Pattern-reversal visual evoked potentials in the hereditary ataxias and spinal degenerations. Ann. Neurol. 9:243, BO~OWI('K, A. R. and J. A. BRODV (1975) Epidemiolog v of neurodegenerative system disorders. In: Vinkem P. J. and G. W. Bruyn (Eds). Handbook of Clinical Neurologv. North-Holland, Amsterdam, Vol. 21:3. BUGE, A., R. ESCOUROLLE, G. RANCUREL, F. GRAY anO B, F. PERTUISET (1979) La paraplegie spasmodique familiale de Strt~mpell-Lorrain (P.S.F.) Une nouvelle observation anatomo-clinique. Rev. Neurol. (Paris) 135:329. COLON, E,, W. RENtE~ and v. GABREICLS(1979) Propagation defects in somatosensor v evoked responses in children. In: Lechner, H. and A. Aranibar (Eds). EEG and Clin. Neurophys. Elsevier, North-Holland,Amsterdam, 526:306. ER~, w. (1895) Ueber heredit~ire spastische Spinalparalyse. Dtsch. Z. Nervenheilk. 6:137. HSrtER, C. M. (1977) Pure spastic paralysis of corticospinal origin. Canad. J. Neurol. Sci. 4:251. GREENFtELD, J. G. (1954) The spinocerebellar degenerations. Blackwell, Oxford. HAPPEL, L. T., H. ROTHSCHILD and c. GARCIA (1980) Visual evoked potentials in two forms of hereditary spastic paraplegia. Electroencephalogr. Clin. Neurophysiol. 48:233.
253 HOLMES, G. L. and a. A. SHAYWITZ (1977) Strumpell's pure familial spastic paraplegia: case study and review of the literature. J. Neurol. Neursosurg. Psychiat. 40: 1003. LIVINGSTONE, I. R., F. L. MASTAGLIA, R. EDIS and J. w. HOWE (1981) Pattern visual evoked responses in hereditary spastic paraplegia. J. Neurol. Neursorug. Psychiat. 44:176. NEWMARK,L. (1906) Pathologisch-anatomischer Befund in einem weiteren Falle von famili~irer spastischer Paraplegie. Dtsch. Z. Nervenheilk. 31:224. ROTHSCHILD, H., L. HAPPEL, D. RAMPP and E. HACKETT (1979) Autosomal recessive spastic paraplegia: evidence for demyelination. Clin. Genet. 15:356. SACK JR., G.H., C. A. HUETHER and N. GARG (1978) Familial spastic paraplegia-Clinical and pathologic studies in a large kindred. Johns Hopkins Med. J. 143:117. SCHWARL G. A. and C.-N. LIU (1956) Hereditary (familial) spastic paraplegia. Further clinical and pathologic observations. Arch. Neurol. Psychiat. 75:144. THOMAS, P. K., J. G. R. JEFFERYS, 1. S. SMITH and D. LOULAKAKIS(1981) Spinal somatosensory evoked potentials in hereditary spastic paraplegia. J. Neurol. Neurosurg. Psychiat. 44:243. THURMON, T. F., B. A. WALKER,C. I. SCOTTand M. H. ABBOTH(1971) Two kindreds with a sex-linked recessive form of spastic paraplegia. In: The clinical delineation of birth defects. Williams and Wilkins, Baltimore~ Vol. 6:219. ZATZ. M., C. PENHA-SERRANOand a. A. OTTO (1976) X-linked recessive type of pure spastic paraplegia in a large pedigree: absence of detectable linkage with Xg. J. Med. Genet. 13:217.
LIST OF PUBLICATIONS ABOUT PATIENTS WITH RECESSIVELY INHERITED PURE SPASTIC PARAPLEGIA SCH~LE, A. (1893) Die Lehre yon der spastischen Spinalparalyse. Dtsch. Z. Nervenheilk. 4:161. ERB, W. (1895) Ueber heredit~ire spastische Spinalparalyse. Dtsch. Z. Nervenheilk. 6:137. KRAFT-EBBING, R. (1900) Ueber infantile famili~ire spastische Spinalparalyse. Dtsch. Z. Nervenheilk. 17:87. JONES, E. (1907) Eight cases of hereditary spastic paraplegia. Rev. Neurol. Psychiat. 5:98. SCHULTZE, F. (1926) Zur Lehre v o n d e r spastischen Gliederstarre und der sogenannten 'spastischen spinalen Paralyse'. Dtsch. Z. Nervenheilk. 92:161. ULLA, J. (1945) Un caso de presentation familiar de paralisi espinal espasmodica. Med. Madrid 13:435. FREUND, J. (1949) Crber spastische Spinalparalyse (Strtimpell) bei einem Brtiderpaar. Dtsch. Z. Nervenheilk. 161:337. RITTER, S. (1959) Au sujet de la parapar6sie spastique familiale de Strumpell. Zhurnal Neuropatologii i Psikhiatrii Imeni S.S. Korsakova (Moskva) 59:525. OZSV/kTH, K. (1968) Paralysis spinalis spastica familiaris. Dtsch. Z. Nervenheilk. 193:287. MEYER, D. W. and H. C. HOPF (1971) Beobachtungen tiber die adulte Form der recessiv-erblichen spastischen Spinalparalyse. Z. Neurol. 199:256. MCLEOD, J. G., J. A. MORGAN and c. REYE(1977) Electrophysiological studies in familial spastic paraplegia. J. Neurol. Neurosurg. Psychiat. 40:611. VERNEA,J. and G. R. SYMINGTON (1977) The late form of pure familial spastic paraplegia. Proc. Aust. Assoc. Neurol. Vol. 14:37. HARDING, A. E. (1981) Hereditary 'pure' spastic paraplegia: a clinical and genetic study of 22 families. J. Neurol. Neurosurg. Psychiat. 44:87 I.