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Familial communicating syringomyelia
Journal of the Neurological Sciences, 1978, 36:135-146 © Elsevier/North-Holland Biomedical Press
135
FAMILIAL COMMUNICATING SYRINGOMYELIA*
S. GIMENEZ-ROLD./~N, C. BENITO and DOLORES MATEO Departments of Neurology and Neuroradiology, Ciudad Sanitdria Provincial "Francisco Fratwo", Doctor Esquerdo 46, Madrid (Spain)
(Received 29 September, 1977)
SUMMARY Classical cervical syringomyelia was found in 3 members of one family. All 3 underwent air myelogram, and a Chiari malformation type I and postural collapse of the spinal cord was found in each case. An affected 7-year-old boy was discovered after a clinical and radiological survey of 8 first-degree relatives on the basis of mild scoliosis, pyramidal tract signs in the lower limbs and enlarged sagittal diameter of the cervical canal. One other member had basilar impression of the skull but no neurological abnormalities. No positive correlation was found between either the size of the cystic cord enlargement or descent of the ectopic tonsils with the duration or severity of the neurological findings. Suboccipital decompressive craniotomy and upper cervical laminectomy in one case was followed by improvement in strength and sensation 1 year later. Progression in familial syringomyelia appears to occur through a mechanism identical to that in the sporadic form and surgery is therefore also indicated. In affected families, routine survey of close relatives for abnormal neurological signs, and radiological evidence of scoliotic deformity of the spine, enlarged cervical canal and bone abnormalities at the craniovertebral junction may prove valuable for early detection. A dominantly inherited, genetically determined malformation seems to be the probable mechanism of inheritance in this family.
INTRODUCTION Communicating syringomyelia is currently considered to be a non-inherited developmental disorder of the spinal cord, most frequently found in association with a Chiari type I malformation. Even though its relationship to other developmental disorders, such as the dysraphic states, many of which are genetically determined, is * Read in part at the 1lth World Congress of Neurology, Amsterdam, September 1977.
136 frequently emphasised (Gardner 1973), recent reports do not mention its familiai occurrence (Barnett, Foster and Hudgson 1973; Gardner 1973; Hertel, Kramer and Placzek 1973). Most of the reported familial cases refer to patients with so-called hereditary lumbosacral syringomyelia, most of whom would probably be better regarded as forms of hereditary sensory neuropathy (Kino 1927; Mankowsky and Czerni 1933; Mueller and Sugar 1943), spinal dysraphism (Alajouanine and Mozziconacci 1933) and amyloid neuropathy (Barraquer-Ferr6 and De Gispert 1936). In the literature only 5 families can be found in which cervical syringomyelia appears to be the correct diagnosis on clinical grounds (Barr6 and Reys 1924; Van Bogaert 1929; Wild and Behnert 1964; Bentley, Campbell and Kauffmann 1975). A full radiological investigation was not performed in all these cases and there is no definite evidence for including familial cases in the communicating type (Williams 1969). Indeed, some 30 ~ of otherwise classical syringomyelia fail to show ectopic tonsils on myelography (Barnett et al. 1973) and it remains uncertain whether such cases would be better regarded as "primary syringomyelia" in Greenfield's terminology (Hughes 1976), an ill-defined degenerative condition of the spinal cord. As only the communicating variety should be suitable for surgical treatment, it is of interest properly to classify the familial cases. Three members from the same family suffering from classical syringomyelia are described. On air myelogram they were found to have ectopic tonsils and postural collapse of the spinal cord, suggesting that each patient had the communicating form of the disease. Furthermore, routine family survey on a clinical and radiological basis resulted in early detection of an asymptomatic member. REPORT OF A FAMILY
Family pedigree The clinical and radiological details of the 3 affected members are described individually below. Once the propositus (IV-23)and her father (111-16)were known to suffer from the disease (Fig. 1) we planned to examine as many members of this family as possible. All members had been born and lived in a town of 4200 inhabitants, 50 km outside Madrid. Consanguineoosmarriageswere not known in the family. Information was obtained from 46 members of paternal branch, and 19 members on the maternal side. Eight members from the two involved generations were examined clinically and radiologically. The 3 cases with evidence of spinal cord disease underwent gas myelography. Four individuals on the maternal side were known to have essential tremor, but no other case could be traced with symptoms suggesting syringomyelia. The two local practitioners were contacted, but no new cases were known in the area.
Radiologieal investigations Eight individuals from generations III and IV underwent a routine battery of radiological examinations. Basilar impression of the skull was evaluated on plain tomograms by means of Chamberlain's line, normal values being those given by Zaragoz_A(1974) (0.215 d: 2.64 ram) in Spain on 200 subjects. The sagittal diameter o f the cervical spine and the i n t e ~ i e u l a r distances were measured according to Hertel (1973), and the seoliotic curvatures were evaluated on teteradiographic films of the spine as described by Cobb (1948). Gas myelogram was performed on affected members following Roth's method (1962). A collapsing cord sign was specifically looked for by tilting the patient lying on one side 15 ° head-up and 15 ° head-down (Heinz, Schlesinger and Potts 1966; Bradac 1972); All studies were carried out with a Mimer III eraniograph. As seen from Table 1, except for case III-17 who had mild basilar impression of the skull, only the 3 cases with clinical evidence of spinal cord disease had radiological abnormalities other than
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138 TABLE 1 RAD1OLOGICAL SURVEY OF THE FAMILY Radiological findings
Family member IlI-16
IV-23
IV-25
1V-24
111-17 Ill-18
llI-19
111-22
5
--
--
9
--
--
27
21
16
16
17
16
16
C3-C6
C6-T1
C4-D6
C5
C4-C6
C5-C6
C4-C6
30 Left
30 Left
--
Spina bifida
5 Yes C2-T2
8 No C2-T2
Basilar impression of the skull Tip of the odontoid process over Chamberlain's line (ram)
Cervical spine Sagittal enlargement of the canal (ram) 20 Site of maximal enlargement C3-C6
Seoliotic deformity Scoliotic angle (°) Side of convexity
Other malformations
26 Right -
-
Air myelogram Ectopic cerebellar tonsils (mm) Ventricular filling Collapsing cord extent Postural cord variation (mm)
6 No C3-T1 3
3
8
contrast studies. Scoliosis occurred in all 3 cases and the two younger patients had enlarged sagittal diameter of the cervical spine and, in addition, case IV-23 had a moderate degree of basilar impression and case IV-25 had spina bifida.
Case reports Case 1 (111-16). This 50.year-old farmer was the father of the propositus (case 2, IV-23) and had been diagnosed as having syringomyelia 33 years before. Initial symptoms consisted in painless injuries and delayed healing of the fingers of his right hand. Weakness and wasting progressed slowly during the next 2 years, when a 10-day course of radiation therapy was applied over the lower cervical area. Some subjective improvement in sensation and arrest of his condition was claimed. In the ensuing years he suffered frequent unnoticed burns and minor injuries on this hand, but no new symptoms developed. He had mild dorsal scoliosis. Cranial nerves were normal except for a right ocular sympathetic paralysis. Moderate wasting of the distal right forearm muscles and dorsal interossei and some clawing of the little finger were observed. A classical main succulente was found on the right hand, exhibiting skin thickening, callosities and multiple scars, Stretch reflexes were abolished in the right arm but were normal in the left arm and in the lower limbs, and the plantars were flexor. There was an area of dissociated anaesthesia involving the C5 to TI dermatomes on the right. Radiologicalexamination. A 26 ° dextroconvex scoliosis of the dorsal spine was demonstrated. The craniovertebral junction was free from abnormalities and the cervical canal was not e~arged. On air myelogram the tonsils appeared 6 m m below the foramen magnum level. The cord had a ribbon-like appearance, but in the sitting position a 3 m m collapse was observed extending from the C3 segment to T1 (Fig. 2). Case 2 (1V-23). This 17-year-old girl, daughter of case 1, was seen after a 10-month history of Raynaud's phenomenon in her left hand, followed by weakness of the fingers, wasting of the hypothe-
139
Fig. 2. Gas myelogram of case 1 (III-16) showing a localized collapse of the spinal cord (arrow) in the sitting position (A), and appearance in the lying position (B). Ectopic cerebellar tonsils are clearly shown. nar muscles and abnormal flexion of the little finger. She had received multiple accidental painless injuries and burns on her hand. On examination she was found to have mild scoliosis, the convexity being towards the left. The cranial nerves appeared normal. There was diffuse wasting of the left hand, more marked on the hypothenar eminence, clawing of the fourth and fifth fingers and atrophy of the dorsal interossei. A blister from a recent painless burn and some scars were noticed. On the left the biceps reflex was absent and the triceps was decreased. No abnormalities were found on the right arm, except for a mild first dorsal interosseus muscle atrophy. There was no weakness of the lower limbs, but hyperactive
140
Fig. 3, Gas myelogram of case 2 (IV-23) showing moderate cystic cord expansion (A) and extensive collapse (B). stretch reflexes and a clasp-knife phenomenon were found on both sides, more marked on the left. Both plantars were flexor. There was complete anaesthesia for pain and temperature in a half-cape suspended distribution extending from C2 to T6 dermatomes on both sides, but other sensory modalities were spared. Radiological examination. The tip of the odontoid process was 5 mm above Chamberlain's line. The sagittal diameter of the cervical spine was moderately enlarged from C3 to C6. A 30 ° levoconvex scoliosis with its apex at the T4 vertebral body was seen on a spine teleradiogram~ The cervical cord was grossly enlarged on air myelography, collapsing 3 mm when the patient's head was tilted
141
Fig. 4. Radiology of the spine in case 3 (IV-25) showing levoconvex dorsal scoliosis (.4), enlarged cervical canal (B), and normal craniovertebral junction (C). up 15 °. The tip of the tonsils appeared 5 m m below the foramen magnum level (Fig. 3). A suboccipital decompressive craniotomy with enlargement of the posterior rim of the foramen magnum and laminectomy of C1 and C2 was performed (Prof. P. Peraita). Both cerebellar tonsils had descended to the C2 level, and the cord was grossly cystic. Aspiration yielded colourless cerebrospinal fluid with a normal protein content. The outlets of the fourth ventricle were opened, and the obex plugged with a piece of muscle. On a follow-up examination a year later she claimed to be improved in hand strength and functional capacity for daily activities. The most conspicuous changes on examination were a marked reduction in the previous areas of dissociated anaesthesia, which were now restricted to the left arm from C6 to C8 and on the ulnar side of the right arm distally. Previously hyperactive deep reflexes were now normal and spasticity had almost disappeared. Case 3 (1V-25). This boy was asymptomatic at the age of 7, though his parents commented he had had some scoliosis from an undetermined age. A dextroconvex scoliosis was found upon examination, but no other skeletal anomalies. Stretch reflexes were normal in the upper limbs, and there was no muscle atrophy. Electrophysiologically, however, giant motor unit muscle potentials suggesting
142
Fig. 5. Gas myelogram of case 3 (IV-25). There is a grossly expanded cord (.41 and marked postural collapse (B). Cerebellar tonsils at the C1 level can be noticed.
chronic motor neurone damage were recorded from the right abductor pollicis brevis muscle (Dr. A. Esteban). Strength and muscle tone were normal in the lower limbs, but there were hyperactive stretch reflexes and bilateral extensor plantar responses. Cooperation for sensory evaluation was fairly good and this was clearly normal. Radiologicalfindings. The abnormalities found in this boy, both in the study of the cervical spine, degree of scoliosis and on gas myelogram were much more severe than those found in his father and sister. The sagittal diameter was grossly enlarged, being maximal between C6 and T1. He had a 30 ° levoconvex scoliotic deformity with the apex at the T9 vertebral body (Fig. 4). In addition there was spina bifida involving the L5 and S1 spinous processes. On myelogram (Fig. 5) a large cyst was found,
143 showing a 8 mm collapse at the sitting position. A severe degree of Chiari type I malformation was also seen, the tonsils descending below the foramen magnum rim 8 mm. Because of the mild nature of the symptoms, his parents preferred to delay any surgical attempt. A year later he was re-examined and the neurological signs appeared unchanged. DISCUSSION
The man and two of his children described here had the classical clinical picture of cervical syringomyelia. In two of them the disorder began during early youth, while the other case was a 7-year-old boy detected after a family survey. Here the neurologic abnormalities consisted in pyramidal tract signs in the lower limbs with bilateral Babinski sign, which are known to be the earliest abnormalities found in this condition (Foster and Hudgson 1973; Hertel et al. 1973). In addition, all 3 cases had scoliosis and other skeletal deformities, including enlarged sagittal diameter of the cervical canal in the two younger patients, basilar impression of the skull in case 2, and spina bifida in case 3. The progression of the disease was rapid in the propositus with a 10-month history of moderately severe hand weakness and atrophy, while in her father the disease appeared to be arrested for 31 years. Finally, no evidence of progression was observed in the young boy examined a year later. On air myelogram, cystic expansion of the spinal cord with postural collapse of variable severity and a Chiari type I malformation was documented in each of the 3 affected members. The size of the cord expansion varied greatly and correlated poorly with the clinical course of the disease. A minor collapsing cord sign was apparent in the arrested case, but it was quite extensive in the asymptomatic young boy. On the other hand, ectopic tonsils were demonstrated in each patient and this was verified on operation in case 2. Neither the appearance of the collapsing cord sign (Conway 1967; Ellertsson and Greitz 1970), nor the Arnold-Chiari deformity (Gardner and Goodall 1950; Appleby, Foster, Hankinson and Hudgson 1968) differed from those usually encountered in sporadic communicating syringomyelia. Accordingly, from a pathogenetic point of view the identity of both conditions may be assumed. We do not know whether the Chiari type I anomaly was the only malformation present in the 3 family members, as a congenital hydromyelic cavity probably existed in at least the youngest patient. This probably occurs in many cases of syringomyelia, so the term hydrosyringomyelia is preferred by some authors (Hall, Muller and Campbell 1975). Nevertheless, the basic point is that the condition may progress later in life as the developmental abnormality at the foramen magnum region impairs the cerebrospinal fluid pathways resulting in persistent dilatation of the central canal under pressure (Williams 1976). If such an assumption is correct, the implication is that surgery may also be indicated in the familial forms and, certainly, a definite improvement followed operation in one of our cases. There are few records of familial syringomyelia having an adequate radiological examination and no generalization can be drawn from our own findings. Only one patient from each of the two families reported by Bentley et al. (1975) was submitted to positive contrast myelography. Some obstruction to the contrast at the foramen magnum was described on each case, though definite evidence was not documented.
144 Van Bogaert (1929) reported the autopsy findings from a woman who developed symptoms suggesting a left cerebellar tumour. This occurred after a l 1-year history ot" painless ulcers and spontaneous finger amputations on both hands, weakness and atrophy and a "suspended" type of dissociated thermoanalgesia. The patient's sister had classical syringomyelia. Pathologically, an arachnoid cyst on the left cerebellar hemisphere and cavitation of the spinal cord was found, but a prolapse of the tonsils was not described. The possibility therefore exists that not every familial case is ~ssociated with a Chiari anomaly. The skeletal abnormalities in the 3 affected individuals do not differ from those commonly encountered in the sporadic form of the disease. The interest rests in the fact that they may be present from an early stage of the disease, and certainly the enlarged cervical canal and the scoliosis of the spine were readily recognized during the radiological survey of the family. The two younger patients had an enlarged cervical canal as is frequently found in syringomyelia with onset below the age of 30 (Wells, Spillane and Bligh 1959; Hertel et al. 1973), and in those with paraparesis as the presenting symptom (Hertel et al. 1973). Environmental as well as genetic factors could have given rise to the same basic developmental defect in each of the involved members in this family. Hertel, Hild and M6nninghoff (1972) reported a concentration of cases of syringomyelia in some small villages in the Rhine valley and Eastern Franconia in Germany, suggesting that an unidentified environmental factor could be responsible. We were unable to detect further cases from the same area where this family was born. As in hydrocephalus secondary to congenital aqueduct stenosis, an identical effect on the phenotype can result from genetic factors, as in X-linked hydrocephalus (Bickers and Adams 1949) as from exogenous factors (Edwards 1958). The most likely mode of inheritance in this family is autosomal dominant, similar to familial basitar impression, another related malformation which can be observed either isolated (Bull, Nixon and Pratt 1955; Morariu and Taranu 1968; Sajid and Copple 1968) or in association with syringomyelia (Metzger, Messing and Simon 1962; Paradis and Sax 1972). Nevertheless Wild and Behnert (1964) have observed syringomyelia in monozygotic twins, and there are a number of reports in which the disease was restricted to siblings (Barr6 and Reys 1924; Van Bogaert 1929; Bentley et al. 1975) indicating that different forms of inheritance may also occur. A familial form of communicating syringomyelia appears well established. As shown, family surveys may be rewarding as previously undetected cases can be found on the basis of mild abnormal neurological signs and radiological findings such as scoliosis and enlarged cervical canal. As in the sporadic form, the familial cases can also be improved by surgery when the cerebrospinal fluid pathways from the fourth ventricle are restored.
145 REFERENCES Alajouanine, Th. and P. Mozziconacci (1939) Un cas de syndrome syringomy61ique lumbo-sacr6 familial avec spina bifida, Rev. neurol., 72: 739-744. Appleby, A., J. B. Foster, J. Hankinson and P. Hudgson (1968) The diagnosis and management of the Chiari anomalies in adult life, Brain, 91 : 131-140. Barnett, H. J. M., J. B. Foster and P. Hudgson (1973) Syringomyelia, Saunders, London. Barraquer-Ferr6, L. and I. De Gispert (1936) Die Syringomyelie, eine famili/ire und heredit~ire Krankheit (13 F~ille in 2 Generationen derselben Familie), Dtsch. Z. Nervenheilk., 141 : 146-157. Barr6, J. A. and Reys (1924) Syringomy61ie chez le fr6re et la soeur, Rev. neurol., 1 : 521-530. Bentley, S. J., M. S. Campbell and P. Kauffmann (1975) Familial syringomyelia, J. NeuroL Neurosurg. Psychiat., 38: 346-349. Bickers, D. S. and R. D. Adams (1949) Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus, Brain, 72: 246-262. Bradac, G. B. (1972) The value of gas myelography in the diagnosis of syringomyelia, Neuroradiology, 4: 41-46. Bull, J., W. L. B. Nixon and R. T. C. Pratt (1955) The radiological criteria and familial occurrence of primary basilar impression, Brain, 78: 229-247. Cobb, J. R. (1948) Outline for the study of scoliosis. In: J. W. Edwards (Ed.), Instructional Course Lectures, American Academy of Orthopaedic Surgeons, Ann Arbor, Mich. Conway, L. W. (1967) Hydrodynamic studies in syringomyelia, J. Neurosurg., 27: 501-504. Edwards, J. H. (1958) Congenital malformations of the central nervous system in Scotland, Brit. J. prey. soc. Med., 12: 115-126. Ellertsson, A. B. and T. Greitz (1970) The distending force in the production of communicating syringomyelia, Lancet, 1 : 1234. Foster, J. B. and P. Hudgsen (1973) The radiology of communicating syringomyelia. In: J. N. Walton (Ed.), Syringomyelia, (Major Problems in Neurology, Vol. 1), Saunders, London, pp. 50-63. Gardner, W. J. (1973) The Dysraphic States, from Syringomyelia to Anencephalus, Excerpta Medica, Amsterdam. Gardner, W. J. and R. J. Goodall (1950) The surgical treatment of Arnold-Chiari malformation in adults, J. Neurosurg., 7: 199-206. Hall, P. V., J. Muller and R. L. Campbell (1975) Experimental hydrosyringomyelia, ischemic myelopathy and syringomyelia, J. Neurosurg., 43: 464-470. Heinz, E. R., E. B. Schlesinger and D. G. Ports (1966) Radiological signs of hydromyelia, Radiology, 86: 311-319. Hertel, G. (1973) The width of the cervical spinal canal and the size of the vertebral bodies in syringomyelia. A statistical comparative study, Europ. Neurol., 9: 168-182. Hertel, G., J. Hild and H. M6nninghoff (1972) Geomedizinische Untersuchungen fiber die Verbreitung der Syringomyelie in Deutschland, Z. NeuroL, 202: 295-306. Hertel, G., S. Kramer and E. Placzek (1973) Die Syringomyelie. Klinische Verlaufsbeobachtungen bei 323 Patienten, Nervenarzt, 44: 1-13. Hughes, J. T. (1976) Syringomyelia and syringobulbia. In: W. Blackwood and J. A. N. Corsellis (Eds.), The Greenfield's Neuropathology, 3rd. ed., Edward Arnold, Ltd., Edinburgh, pp. 668-674. Kino, F. (1927) 1Slber heredo-famili/ire Syringomyelie. Zugleich ein Beitrag zur topischen Gliederung in Querschnitt des Vorderhorns, Z. ges. NeuroL, 107: 1-15. Mankowsky, B. N. and L. I. Czerni (1933) Zur Frage fiber die Heredit/it der Syringomyelie, Z. ges. NeuroL, 143 : 701-712. Metzger, J., R. Messing and J. Simon (1962) Cas familial d'anomalie de la charni6re occipito-atloidienne. Syndrome syringomy61ique chez la m6re, troubles bulbaires frustes chez la fille, Rev. neurol., 106: 767-768. Morariu, M. and A. Taranu (1968) Impression basilaire primaire dans deux families. Etude clinique, radiologique et g6n6tique, Acta neuroL belg., 68: 814-821. Mueller, C. R. and S. J. Sugar (1943) Familial syringomyelia. J. Amer. med. Ass., 122: 743-744. Paradis, R. W. and D. S. Sax (1972) Familial basilar impression, Neurology (Minneap.), 22: 554-560. Roth, G. (1962) My61ographie gazeuse par refoulement, une nouvelle m6thode, J. RadioL Electrol., 43 : 831-838. Sajid, M. H. and P. J. Copple (1968) Familial aqueductal stenosis and basilar impression, Neurology (Minneap.), 18 : 260-262.
146 Van Bogaert, L. (1929) Cyste c6r6belleux associe ~ la syringo-my61o-bulbie chez une malade don~ !:~ soeur pr6sente une syringomy61ie cervicale typique, J. Neurol. Psychicm, 29: 146- 152. Wells, L. E. C., J. D. Spillane and A. S. Bligh (1959) The cervical spinal canal in syringomyelia, B,'~:i~t. 82: 23~-0. Wild, H. and J. Behnert (1964) Konkordante Syringomyelie mit okzipito-zervikaler Dysplasie bci eineiigem Zwillingspaar, Miinch. reed. Wschr., 106: 1421-1428. Williams, B. (1969) The distending force in the production of "communicating syringomyelia", Lancet, 2: 189-193. Williams, B. (1976) Cerebrospinal fluid pressvre changes in response to coughing, Brain, 99:331 346. Zaragoz~i, E. (1974) Malformaei6nes de la Charnela Occipito-cervical y sus Correlaci6nes Clinic~s, Instituto Nacional de Previsi6n, Madrid.
135
FAMILIAL COMMUNICATING SYRINGOMYELIA*
S. GIMENEZ-ROLD./~N, C. BENITO and DOLORES MATEO Departments of Neurology and Neuroradiology, Ciudad Sanitdria Provincial "Francisco Fratwo", Doctor Esquerdo 46, Madrid (Spain)
(Received 29 September, 1977)
SUMMARY Classical cervical syringomyelia was found in 3 members of one family. All 3 underwent air myelogram, and a Chiari malformation type I and postural collapse of the spinal cord was found in each case. An affected 7-year-old boy was discovered after a clinical and radiological survey of 8 first-degree relatives on the basis of mild scoliosis, pyramidal tract signs in the lower limbs and enlarged sagittal diameter of the cervical canal. One other member had basilar impression of the skull but no neurological abnormalities. No positive correlation was found between either the size of the cystic cord enlargement or descent of the ectopic tonsils with the duration or severity of the neurological findings. Suboccipital decompressive craniotomy and upper cervical laminectomy in one case was followed by improvement in strength and sensation 1 year later. Progression in familial syringomyelia appears to occur through a mechanism identical to that in the sporadic form and surgery is therefore also indicated. In affected families, routine survey of close relatives for abnormal neurological signs, and radiological evidence of scoliotic deformity of the spine, enlarged cervical canal and bone abnormalities at the craniovertebral junction may prove valuable for early detection. A dominantly inherited, genetically determined malformation seems to be the probable mechanism of inheritance in this family.
INTRODUCTION Communicating syringomyelia is currently considered to be a non-inherited developmental disorder of the spinal cord, most frequently found in association with a Chiari type I malformation. Even though its relationship to other developmental disorders, such as the dysraphic states, many of which are genetically determined, is * Read in part at the 1lth World Congress of Neurology, Amsterdam, September 1977.
136 frequently emphasised (Gardner 1973), recent reports do not mention its familiai occurrence (Barnett, Foster and Hudgson 1973; Gardner 1973; Hertel, Kramer and Placzek 1973). Most of the reported familial cases refer to patients with so-called hereditary lumbosacral syringomyelia, most of whom would probably be better regarded as forms of hereditary sensory neuropathy (Kino 1927; Mankowsky and Czerni 1933; Mueller and Sugar 1943), spinal dysraphism (Alajouanine and Mozziconacci 1933) and amyloid neuropathy (Barraquer-Ferr6 and De Gispert 1936). In the literature only 5 families can be found in which cervical syringomyelia appears to be the correct diagnosis on clinical grounds (Barr6 and Reys 1924; Van Bogaert 1929; Wild and Behnert 1964; Bentley, Campbell and Kauffmann 1975). A full radiological investigation was not performed in all these cases and there is no definite evidence for including familial cases in the communicating type (Williams 1969). Indeed, some 30 ~ of otherwise classical syringomyelia fail to show ectopic tonsils on myelography (Barnett et al. 1973) and it remains uncertain whether such cases would be better regarded as "primary syringomyelia" in Greenfield's terminology (Hughes 1976), an ill-defined degenerative condition of the spinal cord. As only the communicating variety should be suitable for surgical treatment, it is of interest properly to classify the familial cases. Three members from the same family suffering from classical syringomyelia are described. On air myelogram they were found to have ectopic tonsils and postural collapse of the spinal cord, suggesting that each patient had the communicating form of the disease. Furthermore, routine family survey on a clinical and radiological basis resulted in early detection of an asymptomatic member. REPORT OF A FAMILY
Family pedigree The clinical and radiological details of the 3 affected members are described individually below. Once the propositus (IV-23)and her father (111-16)were known to suffer from the disease (Fig. 1) we planned to examine as many members of this family as possible. All members had been born and lived in a town of 4200 inhabitants, 50 km outside Madrid. Consanguineoosmarriageswere not known in the family. Information was obtained from 46 members of paternal branch, and 19 members on the maternal side. Eight members from the two involved generations were examined clinically and radiologically. The 3 cases with evidence of spinal cord disease underwent gas myelography. Four individuals on the maternal side were known to have essential tremor, but no other case could be traced with symptoms suggesting syringomyelia. The two local practitioners were contacted, but no new cases were known in the area.
Radiologieal investigations Eight individuals from generations III and IV underwent a routine battery of radiological examinations. Basilar impression of the skull was evaluated on plain tomograms by means of Chamberlain's line, normal values being those given by Zaragoz_A(1974) (0.215 d: 2.64 ram) in Spain on 200 subjects. The sagittal diameter o f the cervical spine and the i n t e ~ i e u l a r distances were measured according to Hertel (1973), and the seoliotic curvatures were evaluated on teteradiographic films of the spine as described by Cobb (1948). Gas myelogram was performed on affected members following Roth's method (1962). A collapsing cord sign was specifically looked for by tilting the patient lying on one side 15 ° head-up and 15 ° head-down (Heinz, Schlesinger and Potts 1966; Bradac 1972); All studies were carried out with a Mimer III eraniograph. As seen from Table 1, except for case III-17 who had mild basilar impression of the skull, only the 3 cases with clinical evidence of spinal cord disease had radiological abnormalities other than
137
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.u ° •-
o
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--
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m
138 TABLE 1 RAD1OLOGICAL SURVEY OF THE FAMILY Radiological findings
Family member IlI-16
IV-23
IV-25
1V-24
111-17 Ill-18
llI-19
111-22
5
--
--
9
--
--
27
21
16
16
17
16
16
C3-C6
C6-T1
C4-D6
C5
C4-C6
C5-C6
C4-C6
30 Left
30 Left
--
Spina bifida
5 Yes C2-T2
8 No C2-T2
Basilar impression of the skull Tip of the odontoid process over Chamberlain's line (ram)
Cervical spine Sagittal enlargement of the canal (ram) 20 Site of maximal enlargement C3-C6
Seoliotic deformity Scoliotic angle (°) Side of convexity
Other malformations
26 Right -
-
Air myelogram Ectopic cerebellar tonsils (mm) Ventricular filling Collapsing cord extent Postural cord variation (mm)
6 No C3-T1 3
3
8
contrast studies. Scoliosis occurred in all 3 cases and the two younger patients had enlarged sagittal diameter of the cervical spine and, in addition, case IV-23 had a moderate degree of basilar impression and case IV-25 had spina bifida.
Case reports Case 1 (111-16). This 50.year-old farmer was the father of the propositus (case 2, IV-23) and had been diagnosed as having syringomyelia 33 years before. Initial symptoms consisted in painless injuries and delayed healing of the fingers of his right hand. Weakness and wasting progressed slowly during the next 2 years, when a 10-day course of radiation therapy was applied over the lower cervical area. Some subjective improvement in sensation and arrest of his condition was claimed. In the ensuing years he suffered frequent unnoticed burns and minor injuries on this hand, but no new symptoms developed. He had mild dorsal scoliosis. Cranial nerves were normal except for a right ocular sympathetic paralysis. Moderate wasting of the distal right forearm muscles and dorsal interossei and some clawing of the little finger were observed. A classical main succulente was found on the right hand, exhibiting skin thickening, callosities and multiple scars, Stretch reflexes were abolished in the right arm but were normal in the left arm and in the lower limbs, and the plantars were flexor. There was an area of dissociated anaesthesia involving the C5 to TI dermatomes on the right. Radiologicalexamination. A 26 ° dextroconvex scoliosis of the dorsal spine was demonstrated. The craniovertebral junction was free from abnormalities and the cervical canal was not e~arged. On air myelogram the tonsils appeared 6 m m below the foramen magnum level. The cord had a ribbon-like appearance, but in the sitting position a 3 m m collapse was observed extending from the C3 segment to T1 (Fig. 2). Case 2 (1V-23). This 17-year-old girl, daughter of case 1, was seen after a 10-month history of Raynaud's phenomenon in her left hand, followed by weakness of the fingers, wasting of the hypothe-
139
Fig. 2. Gas myelogram of case 1 (III-16) showing a localized collapse of the spinal cord (arrow) in the sitting position (A), and appearance in the lying position (B). Ectopic cerebellar tonsils are clearly shown. nar muscles and abnormal flexion of the little finger. She had received multiple accidental painless injuries and burns on her hand. On examination she was found to have mild scoliosis, the convexity being towards the left. The cranial nerves appeared normal. There was diffuse wasting of the left hand, more marked on the hypothenar eminence, clawing of the fourth and fifth fingers and atrophy of the dorsal interossei. A blister from a recent painless burn and some scars were noticed. On the left the biceps reflex was absent and the triceps was decreased. No abnormalities were found on the right arm, except for a mild first dorsal interosseus muscle atrophy. There was no weakness of the lower limbs, but hyperactive
140
Fig. 3, Gas myelogram of case 2 (IV-23) showing moderate cystic cord expansion (A) and extensive collapse (B). stretch reflexes and a clasp-knife phenomenon were found on both sides, more marked on the left. Both plantars were flexor. There was complete anaesthesia for pain and temperature in a half-cape suspended distribution extending from C2 to T6 dermatomes on both sides, but other sensory modalities were spared. Radiological examination. The tip of the odontoid process was 5 mm above Chamberlain's line. The sagittal diameter of the cervical spine was moderately enlarged from C3 to C6. A 30 ° levoconvex scoliosis with its apex at the T4 vertebral body was seen on a spine teleradiogram~ The cervical cord was grossly enlarged on air myelography, collapsing 3 mm when the patient's head was tilted
141
Fig. 4. Radiology of the spine in case 3 (IV-25) showing levoconvex dorsal scoliosis (.4), enlarged cervical canal (B), and normal craniovertebral junction (C). up 15 °. The tip of the tonsils appeared 5 m m below the foramen magnum level (Fig. 3). A suboccipital decompressive craniotomy with enlargement of the posterior rim of the foramen magnum and laminectomy of C1 and C2 was performed (Prof. P. Peraita). Both cerebellar tonsils had descended to the C2 level, and the cord was grossly cystic. Aspiration yielded colourless cerebrospinal fluid with a normal protein content. The outlets of the fourth ventricle were opened, and the obex plugged with a piece of muscle. On a follow-up examination a year later she claimed to be improved in hand strength and functional capacity for daily activities. The most conspicuous changes on examination were a marked reduction in the previous areas of dissociated anaesthesia, which were now restricted to the left arm from C6 to C8 and on the ulnar side of the right arm distally. Previously hyperactive deep reflexes were now normal and spasticity had almost disappeared. Case 3 (1V-25). This boy was asymptomatic at the age of 7, though his parents commented he had had some scoliosis from an undetermined age. A dextroconvex scoliosis was found upon examination, but no other skeletal anomalies. Stretch reflexes were normal in the upper limbs, and there was no muscle atrophy. Electrophysiologically, however, giant motor unit muscle potentials suggesting
142
Fig. 5. Gas myelogram of case 3 (IV-25). There is a grossly expanded cord (.41 and marked postural collapse (B). Cerebellar tonsils at the C1 level can be noticed.
chronic motor neurone damage were recorded from the right abductor pollicis brevis muscle (Dr. A. Esteban). Strength and muscle tone were normal in the lower limbs, but there were hyperactive stretch reflexes and bilateral extensor plantar responses. Cooperation for sensory evaluation was fairly good and this was clearly normal. Radiologicalfindings. The abnormalities found in this boy, both in the study of the cervical spine, degree of scoliosis and on gas myelogram were much more severe than those found in his father and sister. The sagittal diameter was grossly enlarged, being maximal between C6 and T1. He had a 30 ° levoconvex scoliotic deformity with the apex at the T9 vertebral body (Fig. 4). In addition there was spina bifida involving the L5 and S1 spinous processes. On myelogram (Fig. 5) a large cyst was found,
143 showing a 8 mm collapse at the sitting position. A severe degree of Chiari type I malformation was also seen, the tonsils descending below the foramen magnum rim 8 mm. Because of the mild nature of the symptoms, his parents preferred to delay any surgical attempt. A year later he was re-examined and the neurological signs appeared unchanged. DISCUSSION
The man and two of his children described here had the classical clinical picture of cervical syringomyelia. In two of them the disorder began during early youth, while the other case was a 7-year-old boy detected after a family survey. Here the neurologic abnormalities consisted in pyramidal tract signs in the lower limbs with bilateral Babinski sign, which are known to be the earliest abnormalities found in this condition (Foster and Hudgson 1973; Hertel et al. 1973). In addition, all 3 cases had scoliosis and other skeletal deformities, including enlarged sagittal diameter of the cervical canal in the two younger patients, basilar impression of the skull in case 2, and spina bifida in case 3. The progression of the disease was rapid in the propositus with a 10-month history of moderately severe hand weakness and atrophy, while in her father the disease appeared to be arrested for 31 years. Finally, no evidence of progression was observed in the young boy examined a year later. On air myelogram, cystic expansion of the spinal cord with postural collapse of variable severity and a Chiari type I malformation was documented in each of the 3 affected members. The size of the cord expansion varied greatly and correlated poorly with the clinical course of the disease. A minor collapsing cord sign was apparent in the arrested case, but it was quite extensive in the asymptomatic young boy. On the other hand, ectopic tonsils were demonstrated in each patient and this was verified on operation in case 2. Neither the appearance of the collapsing cord sign (Conway 1967; Ellertsson and Greitz 1970), nor the Arnold-Chiari deformity (Gardner and Goodall 1950; Appleby, Foster, Hankinson and Hudgson 1968) differed from those usually encountered in sporadic communicating syringomyelia. Accordingly, from a pathogenetic point of view the identity of both conditions may be assumed. We do not know whether the Chiari type I anomaly was the only malformation present in the 3 family members, as a congenital hydromyelic cavity probably existed in at least the youngest patient. This probably occurs in many cases of syringomyelia, so the term hydrosyringomyelia is preferred by some authors (Hall, Muller and Campbell 1975). Nevertheless, the basic point is that the condition may progress later in life as the developmental abnormality at the foramen magnum region impairs the cerebrospinal fluid pathways resulting in persistent dilatation of the central canal under pressure (Williams 1976). If such an assumption is correct, the implication is that surgery may also be indicated in the familial forms and, certainly, a definite improvement followed operation in one of our cases. There are few records of familial syringomyelia having an adequate radiological examination and no generalization can be drawn from our own findings. Only one patient from each of the two families reported by Bentley et al. (1975) was submitted to positive contrast myelography. Some obstruction to the contrast at the foramen magnum was described on each case, though definite evidence was not documented.
144 Van Bogaert (1929) reported the autopsy findings from a woman who developed symptoms suggesting a left cerebellar tumour. This occurred after a l 1-year history ot" painless ulcers and spontaneous finger amputations on both hands, weakness and atrophy and a "suspended" type of dissociated thermoanalgesia. The patient's sister had classical syringomyelia. Pathologically, an arachnoid cyst on the left cerebellar hemisphere and cavitation of the spinal cord was found, but a prolapse of the tonsils was not described. The possibility therefore exists that not every familial case is ~ssociated with a Chiari anomaly. The skeletal abnormalities in the 3 affected individuals do not differ from those commonly encountered in the sporadic form of the disease. The interest rests in the fact that they may be present from an early stage of the disease, and certainly the enlarged cervical canal and the scoliosis of the spine were readily recognized during the radiological survey of the family. The two younger patients had an enlarged cervical canal as is frequently found in syringomyelia with onset below the age of 30 (Wells, Spillane and Bligh 1959; Hertel et al. 1973), and in those with paraparesis as the presenting symptom (Hertel et al. 1973). Environmental as well as genetic factors could have given rise to the same basic developmental defect in each of the involved members in this family. Hertel, Hild and M6nninghoff (1972) reported a concentration of cases of syringomyelia in some small villages in the Rhine valley and Eastern Franconia in Germany, suggesting that an unidentified environmental factor could be responsible. We were unable to detect further cases from the same area where this family was born. As in hydrocephalus secondary to congenital aqueduct stenosis, an identical effect on the phenotype can result from genetic factors, as in X-linked hydrocephalus (Bickers and Adams 1949) as from exogenous factors (Edwards 1958). The most likely mode of inheritance in this family is autosomal dominant, similar to familial basitar impression, another related malformation which can be observed either isolated (Bull, Nixon and Pratt 1955; Morariu and Taranu 1968; Sajid and Copple 1968) or in association with syringomyelia (Metzger, Messing and Simon 1962; Paradis and Sax 1972). Nevertheless Wild and Behnert (1964) have observed syringomyelia in monozygotic twins, and there are a number of reports in which the disease was restricted to siblings (Barr6 and Reys 1924; Van Bogaert 1929; Bentley et al. 1975) indicating that different forms of inheritance may also occur. A familial form of communicating syringomyelia appears well established. As shown, family surveys may be rewarding as previously undetected cases can be found on the basis of mild abnormal neurological signs and radiological findings such as scoliosis and enlarged cervical canal. As in the sporadic form, the familial cases can also be improved by surgery when the cerebrospinal fluid pathways from the fourth ventricle are restored.
145 REFERENCES Alajouanine, Th. and P. Mozziconacci (1939) Un cas de syndrome syringomy61ique lumbo-sacr6 familial avec spina bifida, Rev. neurol., 72: 739-744. Appleby, A., J. B. Foster, J. Hankinson and P. Hudgson (1968) The diagnosis and management of the Chiari anomalies in adult life, Brain, 91 : 131-140. Barnett, H. J. M., J. B. Foster and P. Hudgson (1973) Syringomyelia, Saunders, London. Barraquer-Ferr6, L. and I. De Gispert (1936) Die Syringomyelie, eine famili/ire und heredit~ire Krankheit (13 F~ille in 2 Generationen derselben Familie), Dtsch. Z. Nervenheilk., 141 : 146-157. Barr6, J. A. and Reys (1924) Syringomy61ie chez le fr6re et la soeur, Rev. neurol., 1 : 521-530. Bentley, S. J., M. S. Campbell and P. Kauffmann (1975) Familial syringomyelia, J. NeuroL Neurosurg. Psychiat., 38: 346-349. Bickers, D. S. and R. D. Adams (1949) Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus, Brain, 72: 246-262. Bradac, G. B. (1972) The value of gas myelography in the diagnosis of syringomyelia, Neuroradiology, 4: 41-46. Bull, J., W. L. B. Nixon and R. T. C. Pratt (1955) The radiological criteria and familial occurrence of primary basilar impression, Brain, 78: 229-247. Cobb, J. R. (1948) Outline for the study of scoliosis. In: J. W. Edwards (Ed.), Instructional Course Lectures, American Academy of Orthopaedic Surgeons, Ann Arbor, Mich. Conway, L. W. (1967) Hydrodynamic studies in syringomyelia, J. Neurosurg., 27: 501-504. Edwards, J. H. (1958) Congenital malformations of the central nervous system in Scotland, Brit. J. prey. soc. Med., 12: 115-126. Ellertsson, A. B. and T. Greitz (1970) The distending force in the production of communicating syringomyelia, Lancet, 1 : 1234. Foster, J. B. and P. Hudgsen (1973) The radiology of communicating syringomyelia. In: J. N. Walton (Ed.), Syringomyelia, (Major Problems in Neurology, Vol. 1), Saunders, London, pp. 50-63. Gardner, W. J. (1973) The Dysraphic States, from Syringomyelia to Anencephalus, Excerpta Medica, Amsterdam. Gardner, W. J. and R. J. Goodall (1950) The surgical treatment of Arnold-Chiari malformation in adults, J. Neurosurg., 7: 199-206. Hall, P. V., J. Muller and R. L. Campbell (1975) Experimental hydrosyringomyelia, ischemic myelopathy and syringomyelia, J. Neurosurg., 43: 464-470. Heinz, E. R., E. B. Schlesinger and D. G. Ports (1966) Radiological signs of hydromyelia, Radiology, 86: 311-319. Hertel, G. (1973) The width of the cervical spinal canal and the size of the vertebral bodies in syringomyelia. A statistical comparative study, Europ. Neurol., 9: 168-182. Hertel, G., J. Hild and H. M6nninghoff (1972) Geomedizinische Untersuchungen fiber die Verbreitung der Syringomyelie in Deutschland, Z. NeuroL, 202: 295-306. Hertel, G., S. Kramer and E. Placzek (1973) Die Syringomyelie. Klinische Verlaufsbeobachtungen bei 323 Patienten, Nervenarzt, 44: 1-13. Hughes, J. T. (1976) Syringomyelia and syringobulbia. In: W. Blackwood and J. A. N. Corsellis (Eds.), The Greenfield's Neuropathology, 3rd. ed., Edward Arnold, Ltd., Edinburgh, pp. 668-674. Kino, F. (1927) 1Slber heredo-famili/ire Syringomyelie. Zugleich ein Beitrag zur topischen Gliederung in Querschnitt des Vorderhorns, Z. ges. NeuroL, 107: 1-15. Mankowsky, B. N. and L. I. Czerni (1933) Zur Frage fiber die Heredit/it der Syringomyelie, Z. ges. NeuroL, 143 : 701-712. Metzger, J., R. Messing and J. Simon (1962) Cas familial d'anomalie de la charni6re occipito-atloidienne. Syndrome syringomy61ique chez la m6re, troubles bulbaires frustes chez la fille, Rev. neurol., 106: 767-768. Morariu, M. and A. Taranu (1968) Impression basilaire primaire dans deux families. Etude clinique, radiologique et g6n6tique, Acta neuroL belg., 68: 814-821. Mueller, C. R. and S. J. Sugar (1943) Familial syringomyelia. J. Amer. med. Ass., 122: 743-744. Paradis, R. W. and D. S. Sax (1972) Familial basilar impression, Neurology (Minneap.), 22: 554-560. Roth, G. (1962) My61ographie gazeuse par refoulement, une nouvelle m6thode, J. RadioL Electrol., 43 : 831-838. Sajid, M. H. and P. J. Copple (1968) Familial aqueductal stenosis and basilar impression, Neurology (Minneap.), 18 : 260-262.
146 Van Bogaert, L. (1929) Cyste c6r6belleux associe ~ la syringo-my61o-bulbie chez une malade don~ !:~ soeur pr6sente une syringomy61ie cervicale typique, J. Neurol. Psychicm, 29: 146- 152. Wells, L. E. C., J. D. Spillane and A. S. Bligh (1959) The cervical spinal canal in syringomyelia, B,'~:i~t. 82: 23~-0. Wild, H. and J. Behnert (1964) Konkordante Syringomyelie mit okzipito-zervikaler Dysplasie bci eineiigem Zwillingspaar, Miinch. reed. Wschr., 106: 1421-1428. Williams, B. (1969) The distending force in the production of "communicating syringomyelia", Lancet, 2: 189-193. Williams, B. (1976) Cerebrospinal fluid pressvre changes in response to coughing, Brain, 99:331 346. Zaragoz~i, E. (1974) Malformaei6nes de la Charnela Occipito-cervical y sus Correlaci6nes Clinic~s, Instituto Nacional de Previsi6n, Madrid.